Untitled

Obsessive Compulsive Disorder:
A Practical Guide
Obsessive Compulsive
Disorder:
A Practical Guide
Naomi Fineberg MA(Cantab), MBBS MRCPsych

Consultant Psychiatrist
East and North Herts Specialist OCD Service
Queen Elizabeth II Hospital
Howlands
Welwyn Garden City
Herts, UK
Donatella Marazziti MD
Psychiatrist
Department of Psychiatry, Neurobiology, Pharmacology and
Biotechnology
University of Pisa
Pisa, Italy
Dan J Stein BSc (Med), MBChB, FRCPC

Director
MRC Unit on Anxiety Disorders
Department of Psychiatry
University of Stellenbosch
Cape Town
South Africa
and Department of Psychiatry
University of Florida
Gainesville FL, USA
Martin Dunitz
Although every effort has been made to ensure that drug doses and other information are
presented accurately in this publication, the ultimate responsibility rests with the prescribing
physician. Neither the publishers nor the authors can be held responsible for errors or for
any consequences arising from the use of information contained herein. For detailed
prescribing information or instructions on the use of any product or procedure discussed
herein, please consult the prescribing information or instructional material issued by the
manufacturer.
© 2001 Martin Dunitz Ltd, a member of the Taylor & Francis group
First published in the United Kingdom in 2001

Paperback edition published in the United Kingdom in 2002
by Martin Dunitz Ltd, The Livery House, 7–9 Pratt Street, London NW1 0AE
Tel.: +44 (0) 20 74822202

Fax.: +44 (0) 20 72670159
E-mail: [email protected]
Website: http://www.dunitz.co.uk
This edition published in the Taylor & Francis e-Library, 2003.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval
system, or transmitted, in any form or by any means, electronic, mechanical, photocopying,
recording, or otherwise, without the prior permission of the publisher or in accordance with
the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any
licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham
Court Road, London W1P 0LP.
A CIP record for this book is available from the British Library.
ISBN 0-203-21289-4 Master e-book ISBN
ISBN 0-203-27007-X (Adobe eReader Format)

ISBN 1 85317 919 1 hardback edition
ISBN 1 84184 174 9 paperback edition
Distributed in the USA by

Fulfilment Center
Taylor & Francis
7625 Empire Drive
Florence, KY 41042, USA
Toll Free Tel: 1-800-634-7064
Email: cserve@routledge ny.com
Distributed in Canada by
Taylor & Francis
74 Rolark Drive
Scarborough
Ontario M1R G2, Canada
Toll Free Tel: 1-877-226-2237
Email: tal [email protected]
Distributed in the rest of the world by

ITPS Limited
Cheriton House
North Way, Andover
Hampshire SP10 5BE, UK
Tel: +44 (0)1264 332424
Email: [email protected]
Composition by Wearset, Boldon, Tyne and Wear

Contents
Dedication vii
Contributors viii
Preface xi
1 Obsessive compulsive disorder: a 1

twenty-first century perspective
Naomi Fineberg and Ann Roberts
2 Assessment of OCD 15
Toby D Goldsmith, Nathan A Shapira and
Wayne K Goodman
3 Obsessive compulsive spectrum 23

disorders: from serotonin to
dopamine and back again
Michael Van Ameringen, Jonathan M Oakman,
Catherine Mancini and Peter Farvolden
4 Unusual symptoms of OCD 37

Dan J Stein, Naomi Fineberg and Brian Harvey
5 OCD and quality of life 51

Lorrin M Koran
6 The role of genetic factors in OCD 61

David L Pauls
7 The neuroanatomy of OCD 77

James V Lucey
8 Integrated pathophysiology 89
Donatella Marazziti
vi OCD: a practical guide
9 Practical pharmacotherapy 103

Joseph Zohar and Naomi Fineberg
10 Psychotherapy in OCD 119

Andreas Broocks and Fritz Hohagen
11 Treatment of refractory OCD 135

Christopher J McDougle and Kelda H Walsh
12 OCD in children and adolescents 153

Martine F Flament and David Cohen
13 An integrated approach to the 167

treatment of OCD
Dan J Stein, Naomi Fineberg and Soraya Seedat
14 Patients’ perspectives on OCD 177

Frederick Toates
Appendix 1: Major rating scales 183
Appendix 2: Consumer 221

organizations involved in OCD
Dedication
In memory of Sidney Fineberg, and with grateful thanks to my mentors,

Barry Everitt, Stuart Montgomery and Philip Cowen, my patients and my
husband, Edwin.
Naomi Fineberg
I dedicate this book to OCD patients who inspired and continue to sus-
tain my interest in their sufference; to my mentor, Professor Giovanni B
Cassano, who shaped and oriented my professional life; and to our editor
and friend, Mrs Ruth Dunitz, who enthusiastically shared with us the
‘adventure’ of developing this book.
Donatella Marazziti
For Heather, Gabriella and Joshua, and with gratitude to the people with
OCD who have contributed their knowledge and time to the research
efforts of the MRC Unit on Anxiety Disorders.
Dan J Stein
Contributors
Andreas Broocks MD, PhD Toby D Goldsmith MD

Medical University of Lübeck University of Florida, College of
Clinic for Psychiatry and Medicine
Psychotherapy Department of Psychiatry
Ratzeburger Allee 160 PO Box 100256
23538 Lübeck Gainesville FL 32610-0256
Germany USA
David Cohen MD Wayne K Goodman MD

CNRS UMR 7593 University of Florida, College of
Hôpital La Salpêtrière Medicine
Pavillon Clérambault Department of Psychiatry
47 boulevard de l’Hôpital PO Box 100256
75013 Paris Gainesville FL 32610-0256
France USA
Peter Farvolden PhD Brian Harvey BPharm, BPharm (Hons),

Centre for Addiction and Mental Health MPharm, PhD
33 Russell Street Department of Pharmacology
Toronto, ON, M5S 2S1 University of Potschefstroom
Canada Potschefstroom
South Africa
Naomi A Fineberg MA(Cantab), MBBS
MRCPsych Fritz Hohagen MD, PhD
East and North Herts Specialist OCD Medical University of Lübeck
Service Clinic for Psychiatry and
Queen Elizabeth II Hospital Psychotherapy
Howlands Ratzeburger Allee 160
Welwyn Garden City 23538 Lübeck
Herts, AL7 4HQ Germany
UK
Lorrin M Koran MD
Martine F Flament MD, PhD Department of Psychiatry and
CNRS UMR 7593 Behavioral Sciences
Hôpital La Salpêtrière and OCD Clinic, Room 2363
Pavillon Clérambault Stanford University Medical Center
47 boulevard de l’Hôpital 401 Quarry Road
75013 Paris Stanford, CA 94305-5721
France USA
Contributors ix
James V Lucey MD, PhD, MRCPsych, FRCPI David L Pauls PhD

Royal College of Surgeons in Ireland Child Study Center and Department of
Department of Psychiatry Psychology
Academic Centre, James Connolly Yale University School of Medicine
Memorial Hospital 333 Cedar Street
Dublin 15 New Haven CT 06510
Ireland USA
Christopher J McDougle MD Ann Roberts MA(Cantab), MBBS MRCGP

Department of Psychiatry MRCPsych
Indiana University School of Medicine East and North Herts Specialist OCD
Clinical Building, room 299 Service
541 Clinical Drive Queen Elizabeth II Hospital
Indianapolis, IN 46202 Howlands
USA Welwyn Garden City
Herts, AL7 4HQ
Catherine Mancini MD UK
Department of Psychiatry and
Behavioural Neurosciences Soraya Seedat MBChB, MMed (Psych)
McMaster University MRC Unit of Anxiety Disorders
Anxiety Disorders Clinic Department of Psychiatry
Hamilton Health Sciences Corporation University of Stellenbosch
McMaster University Medical Centre Cape Town
1200 Main Street West South Africa
Hamilton, ON, L8N 3Z5
Canada Nathan A Shapira MD
University of Florida, College of
Medicine
Donatella Marazziti MD
Department of Psychiatry,
PO Box 100256
Neurobiology, Pharmacology and
Gainesville FL 32610-0256
Biotechnology
USA
University of Pisa
Via Roma, 67
Dan J Stein BSc (Med), MBChB, FRCPC
56100 Pisa
MRC Unit of Anxiety Disorders
Italy
University of Stellenbosch
Jonathan M Oakman PhD
Cape Town
Department of Psychology
South Africa
University of Waterloo
and Department of Psychiatry
Waterloo, ON, N2L 3G1
University of Florida
Canada
Gainesville FL
USA
x OCD: a practical guide
Frederick Toates Dphil, DSc Kelda H Walsh MD

Department of Biological Sciences Department of Psychiatry
The Open University Indiana University School of Medicine
Milton Keynes Riley Hospital for Children
MK7 6AA 702 Barnhill Drive, room 3701
UK Indianapolis, IN 46202
USA
Michael Van Ameringen MD
Department of Psychiatry and Joseph Zohar MD
Behavioural Neurosciences Chaim Sheba Medical Center
McMaster University Division of Psychiatry
Anxiety Disorders Clinic Tel-Hashomer 52621
Hamilton Health Sciences Corporation Israel
McMaster University Medical Centre
1200 Main Street West
Hamilton, ON, L8N 3Z5
Canada
Preface
Obsessive compulsive disorder is now recognized as one of the most

common psychiatric disorders, and as the tenth most disabling of all
medical disorders. Fortunately, major advances in our understanding of
its neurobiological basis and the discovery of robust treatments offer new
hope for people with OCD.
Nevertheless, despite the increased recognition of the prevalence and
morbidity of OCD, and the introduction of effective treatments, people
with OCD continue to remain underdiagnosed and inappropriately
treated. It is important for specialist clinicians to be able to educate the
public about this disorder, and to provide primary care colleagues with
up-to-date information.
In this volume, we attempt to provide a practical guide to the diagno-
sis, assessment, and management of OCD. Summaries of exciting dis-
coveries in the psychobiology of OCD are included, and pathways for
future research considered. This is a book by and for clinicians, and we
hope that it will prove useful in clinical settings.
We would like to thank Ruth Dunitz for encouraging and guiding this
project.
NF, DM, DJS

1
Obsessive compulsive disorder: a twenty-
first century perspective
Naomi Fineberg and Ann Roberts
MACBETH: How does your patient, doctor?

DOCTOr: Not so sick, my lord,
As she is troubled with thick-coming fancies
That keep her from her rest.
(From Shakespeare’s Macbeth, act V scene III; circa 1606)
Throughout history, our conceptualization of obsessive compulsive disor-

der (OCD) has been changing alongside changes in the way we have
viewed the world. With the dawning of the Renaissance in western
Europe, religious explanations based on demonic possession were
superseded by a more humanistic understanding. By the early seven-
teenth century, the obsessions that drove Shakespeare’s Lady Macbeth
to suicide were recognized to be a product of her guilty mind, for which
there was no medical cure.
Obsessions and compulsions were first described in the medical litera-
ture of the early nineteenth century. They were viewed as an unusual
expression of melancholia. By the beginning of the twentieth century, with
the development of psychoanalysis, the focus shifted onto psychological
explanations based on unconscious conflicts, but this did not provide a
useful strategy for treatment. The subsequent application of learning the-
ory to OCD led to the development of effective behavioural treatments in
the 1960s and 1970s.
Compared with the pace of these historical developments, modern under-
standing of OCD has expanded with dramatic speed. The development of
effective medical treatments of OCD has revolutionized the outlook for suf-
ferers and propelled OCD to the forefront of scientific attention. With the
growth of research into the epidemiology, psychopharmacology, neurobiol-
ogy, neuropsychology and genetics of OCD, reviewed throughout this publi-
cation, the emphasis has once again swung back toward a medical model.
As we enter the twenty-first century, we now recognize OCD as a common,
treatable form of major mental disorder.
1
2 OCD: a practical guide
Diagnostic classification
Both the World Health Organization’s International Classification of Dis-
eases, 10th revision (ICD-10) and the American Psychiatric Association’s
Diagnostic and Statistical Manual, 4th edition (DSM-IV) recognize obses-
sions and/or compulsions as the core symptoms of OCD.1,2 Obsessions
are defined as unwanted ideas, images or impulses which repeatedly
enter the individual’s mind. Although recognized as being generated by
the individual, they are egodystonic and distressing. Compulsions are
repetitive stereotyped behaviours or mental acts that are driven by rules
that must be applied rigidly. They are not inherently enjoyable and do not
result in the completion of any useful task. They may or may not be linked
to underlying obsessional thoughts such as worries about contamination
or concerns about harm to others.
In both diagnostic systems either disabling obsessions or compulsions
(or both) will satisfy a diagnosis. The ICD-10 applies a more rigorous
threshold, requiring the symptoms to be present on most days for a
period of at least 2 weeks (Table 1.1). Resistance toward the obsessions
or compulsions need not always be present, and in chronic cases
patients often find that active resistance makes the symptoms worse.
The DSM-IV has prioritized anxiety as a core symptom, and classifies
OCD with the anxiety disorders, even though OCD shares few features
with the other disorders in this group. In contrast, the ICD-10 has fol-
lowed a European tradition in conceptualizing OCD as a ‘stand-alone’
disorder. In the ICD-10, OCD is placed independently within the category
of neurotic, stress-related and somatoform disorders.
Further separation of OCD is likely in the future, informed by the grow-
ing clinical and neurobiological findings that place the disorder at the
heart of a ‘spectrum’ of OCD-related disorders including hypochondriasis,
Table 1.1 ICD-10 criteria for OCD.

A Either obsessions or compulsions (or both) present on most days for a period
of at least 2 weeks
B Obsessions (thoughts, ideas or images) and compulsions share the following

features, all of which must be present:
acknowledged as originating from the mind of the patient, not from outside
repetitive and unpleasant: at least one must be acknowledged as
excessive or unreasonable
resisted (but if very long-standing, resistance may be minimal); at least
one must be unsuccessfully resisted
carrying out the obsessive thought or compulsive act is not in itself
pleasurable
Adapted from ICD-10.1 Reproduced with kind permission of the International Council on OCD. Adapted
from International Council on OCD, Update on OCD (Medical Action Communications, 1995).
A twenty-first century perspective 3
body dysmorphic disorder, trichotillomania, tic disorders and deperson-

alization disorder (see Chapter 3).3,4
How common is OCD?
After the pioneering epidemiological catchment area (ECA) studies car-

ried out by the National Institute of Mental Health in the early 1980s
reported that the prevalence of OCD was substantially higher than
expected,5,6 repeated population studies using similar methods have
demonstrated a lifetime prevalence of 2–3% worldwide.7 Taiwan and
India were the only exceptions, with rates below 1%. If these estimates
are accurate, then OCD affects more than 50 million people in the world
today. The prevalence does not appear to be influenced by socioeco-
nomic status, educational achievement, or ethnicity. The disorder is more
common than schizophrenia, and about half as common as depression
(Table 1.2). Yet the illness remains largely under-recognized, and the
psychosocial and economic costs to society from untreated OCD are
high.8 It is not surprising that the World Health Organization has now rec-
ognized OCD as a public health priority.
While there is little doubt that the ‘hidden epidemic’ of OCD exists, the
actual prevalence of clinically relevant disorder has been called into
question. In the ECA studies lay interviewers were trained to make
DSM-III diagnoses using the Diagnostic Interview Schedule (DIS).5,6 How-
ever, clinical reappraisal of DIS-positive cases resulted in less than 25%
continuing to meet the criteria for OCD.9,10 One explanation is that the
rates of illness reported in the original ECA studies may have been exag-
gerated. Alternatively, the findings may reflect variability in the severity of
the disorder over time. Longitudinal studies in community-based samples
Table 1.2 Prevalence of OCD reported by the NIMH epidemiological

catchment area study.
Prevalence rates
Lifetime (%) 6 months (%)
Major depression 5.2 2.9

OCD 2.5 1.6
Schizophrenia 1.6 0.9
Panic disorder 1.4 0.8
Severe cognitive impairment 1.2 1.2
Anorexia nervosa 0.1 –
In: Robins et al (1984).5 Reproduced with kind permission of the International Council on OCD. Adapted
from International Council on OCD, Update on OCD (Medical Action Communications: Egham, Surrey,
UK 1995).
35
Males
30 Females
25
No. of probands
20
15
10
5
0
6–9 10–12 13–15 16–19 20–24 25–29
Age of onset
Figure 1.1
Age at onset of OCD. Adapted with permission from Rasmussen SA, Eisen JL.
Epidemiology of obsessive compulsive disorder. J Clin Psychiatry (1990); 51: 10–13.14
Copyright 1990 Physicians Postgraduate Press. Reprinted by permission.
have shown that the condition fluctuates above and below the threshold
for OCD at different periods.11 In fact, there appears to be a large pool of
subclinical OCD in the general population, estimated in one study to be
as high as 19%.12
Although most children experience some obsessional symptoms dur-
ing their development, in only a minority do the symptoms develop into
OCD.13 The lifetime prevalence in children has been reported to be
almost as high as in adults, at around 2% (see Chapter 12). Of interest is
the large proportion with obsessions only, exceeding 50% of the OCD
respondents in one of the studies.
Age of onset
Retrospective studies suggest that the mean age of onset of OCD is ear-
lier than that of depression, at around 20 years, with the incidence peak-
ing once in the early teens and again in the early twenties. Males develop
the disorder earlier than females (Figure 1.1).14 Studies looking at chil-
dren and adolescents with OCD reveal a similar pattern, with boys show-
ing a prepubertal onset at around 9 years and girls developing the
disorder around puberty.15
OCD and gender
Obsessive compulsive disorder is more common in women, although the

differences are not as obvious as in depression or other anxiety
disorders. An average female to male ratio of 1.5 : 1.0 is accepted for the
community at large, although the ratio appears roughly equal in the
adolescent population, reflecting perhaps the earlier onset in boys. In
contrast, men predominate in surveys of OCD referrals, possibly reflect-
ing a greater severity in males.
Women during pregnancy and the puerperium are particularly at risk of
developing the disorder. In a study by Neziroglu et al of 59 mothers with
OCD, 23 experienced their symptoms for the first time during
pregnancy.16 In many cases, pre-existing obsessional tendencies are
unmasked and exaggerated by the events surrounding childbirth.
Familial factors
Obsessive compulsive disorder is considered to be one of the most

strongly inherited mental disorders (see Chapter 6).17 Approximately one-
fifth of nuclear family members of OCD sufferers show signs of OCD, and
the younger the sufferer the more likely they are to have a first-degree rel-
ative affected. The clustering of OCD and Tourette’s syndrome (TS)
within families suggests a common inherited factor.
Course and prognosis
The course of the illness can vary from a relatively benign form in which
the patient experiences infrequent, discrete episodes of illness inter-
spersed with symptom-free periods, to malignant OCD, characterized by
unremitting symptoms and substantial social impairment.
In a 40-year prospective follow-up study, reported by Skoog and
Skoog, the authors managed to locate and examine 144 out of 251 OCD
patients who had previously been admitted as inpatients under their care
between 1947 and 1953.18 Given that effective treatments for OCD were
not developed until the end of the study, much of the data is naturalistic.
The authors found that roughly 60% showed signs of general improve-
ment within 10 years of onset of illness, rising to 80% by the end of the
study. However, only 20% achieved full remission even after nearly 50
years of illness; 60% continued to experience significant symptoms; 10%
showed no improvement whatsoever; and another 10% had worsened. In
60% of cases the content of the obsessions shifted markedly over the
follow-up period. One-fifth of those who had shown an early, sustained
improvement subsequently relapsed, even after 20 years without symp-
toms, suggesting early recovery does not rule out the possibility of very
late relapse. Intermittent, episodic disease was common during the early
stage of illness, and predicted a more favourable outcome, whereas
chronic illness predominated in the later years. Early age of onset,
particularly in males, having both obsessions and compulsions or magi-

cal thinking, poor social adjustment, and an early chronic course, pre-
dicted a worse outcome.
A more recent 5-year prospective follow-up study of 100 OCD patients
showed that in spite of the introduction of modern treatments, outcomes
were similar to Skoog and Skoog’s cohort, with only 20% reaching full
remission of their OCD, 50% showing partial remission, and the remain-
der unchanged or worse over 5 years. Less severe illness and being
married were associated with a better outcome.19
Symptoms and subtypes
Most patients suffer a mixture of different obsessions or compulsions.

Surveys have consistently identified contamination fears as the most
common obsession, with concern about harm to others, pathological
doubt, somatic obsessions and the need for symmetry also occurring fre-
quently. Half of all OCD patients admitted for treatment suffer compul-
sions in the realm of repetitive checking or excessive cleaning and
washing (Table 1.3).20 Key themes have been identified that underlie
most symptoms. These include abnormal risk assessment, pathological
doubt and incompleteness.3
Patients with OCD usually retain full insight into the absurdity of their
symptoms, although this is not always the case.21 The DSM-IV singles out
patients with poor insight as a meaningful subgroup. These individuals
have more complex symptomatology, which makes diagnosis more diffi-
cult, and tend to be more severely ill. They have only a limited sense of
the excessiveness and irrationality of their thoughts and behaviours and
are therefore difficult to engage in treatment. They may appear to be
deluded (and hence receive inappropriate treatment) but longitudinal
studies show they do not go on to develop schizophrenia-like illnesses.22
In a cohort of 475 patients with OCD, 27 (6%) displayed lack of insight.23
Differential diagnosis
Mild forms of obsessional behaviour, such as repetitive checking or

superstitious behaviour, commonly occur in everyday life. They only meet
the criteria for OCD if they are time-consuming, or associated with impair-
ment or distress.
Recurrent, intrusive thoughts, impulses and images also occur in other
mental disorders thought to share a relationship with OCD: for example,
the preoccupation with bodily appearance, in body dysmorphic disorder;
with a feared object, in specific phobia; with illness, in hypochondriasis;
or with hair-pulling, in trichotillomania. A diagnosis of OCD should only be
Table 1.3 Phenomenological analysis of 250 OCD inpatients.
Common obsessions (%) Common compulsions (%)
Behaviours Mental acts
Contamination fears (45%) Checking (63%) Covert counting (36%)

Repetitive doubts (42%) Washing (50%)
Somatic obsessions (36%) Need to confess (36%)
Need for symmetry (31%) Ordering/symmetry (31%)
Aggressive impulses (28%) Hoarding (18%)
Repeated sexual imagery (26%)
Multiple obsessions (60%) Multiple compulsions (48%)
Adapted from Rasmussen and Eisen.20

made if there are also unrelated obsessive-compulsive symptoms, in

which case more than one diagnosis may be warranted.
Activities such as preoccupation with eating, sex, shopping and gam-
bling are not considered genuine compulsions because they are not
egodystonic, and the individual usually only tries to resist because of the
adverse consequences.
Comorbidity
Depression
Obsessive compulsive disorder shares comorbidity with a range of DSM
Axis I and II disorders (Table 1.4), the most common of which is major
depression. A diagnosis of OCD can be made in the presence of comor-
bid depression as long as the ruminations are not restricted to depres-
sive themes. The ECA studies revealed that a third of adult patients with
OCD also met the diagnostic criteria for major depression at the time of
interview, and that three-quarters had suffered a major depressive
episode at some point during the course of their OCD. Moreover, 12% of
patients with a diagnosis of major depression also shared a lifetime diag-
nosis of OCD. In a large cohort study of children and adolescents with
OCD, a third had a history of current or lifetime depression. The depres-
sion was equally likely to predate or follow the OCD.24
Studies have also shown higher rates of suicidal behaviour compared
with patients suffering from other mental disorders. The suicidal behav-
iour appeared to be independent of concurrent depression.25
Many patients only present to doctors for treatment of their comorbid
depression. In these cases it is important that the OCD is not missed,
because the depression will only respond if the OCD is treated as well.26
Table 1.4 Comorbidity in OCD.

Diagnosis Current Lifetime
(%) (%)
Major depression 31 67
Specific phobia 7 22
Social phobia 11 18
Eating disorder 8 17
Alcohol abuse 8 14
Panic disorder 6 12
Tourette’s syndrome 5 17
Adapted from Rasmussen and Eisen.20

Tourette’s syndrome
Tourette’s syndrome (TS) is often complicated by comorbid OCD, with
estimates ranging from 35% to 50%. The incidence of TS in OCD is lower
(5–7%), although tics are reported in 20–30% of individuals with OCD. It
has been postulated that some forms of OCD may represent a ‘forme
fruste’ of TS. ‘Uncomplicated’ OCD patients have been reported to expe-
rience more contamination fears and cleaning and washing rituals, com-
pared with obsessional patients with comorbid TS who reported more
obsessive compulsive symptoms overall, and suffered more from aggres-
sive, religious and sexual obsessions, forced touching, checking, count-
ing and evening-up rituals.27,28 Factor analysis of a large cohort of OCD
sufferers identified four separate symptom clusters (obsessions and
checking, symmetry and ordering, cleanliness and washing, and hoard-
ing obsessions and compulsions) each with a different degree of heri-
tability, suggesting the existence of biologically distinct subtypes.29 This
model needs to be reconciled with the finding that in most patients,
changes occur in the content of the symptoms during the natural course
of the illness.18
Obsessive compulsive personality disorder

The essential feature of obsessive compulsive personality disorder (OCPD)
is a pervasive preoccupation with orderliness, perfectionism and mental
and interpersonal control, at the expense of flexibility, openness and effi-
ciency, which develops by early adulthood and persists (Table 1.5).2
Unlike OCD, these traits are egosyntonic, and unacceptable obsessions
and compulsions are absent.
According to psychoanalytical theory, OCD and OCPD share the same
unconscious defence mechanisms, and OCD is thought to evolve out of
OCPD. However, epidemiological studies consistently show that whereas
Table 1.5 Diagnostic specifiers for DSM-IV 301.4: obsessive compulsive

personality disorder.
Preoccupation with details, rules, lists, order, organization or schedules
Perfectionism that interferes with task completion
Excessive devotion to work to the exclusion of leisure
Overconscientiousness, scrupulosity and inflexibility
Inability to discard worthless objects
Reluctance to delegate, needing to be in control
Miserliness
Rigidity and stubbornness
Adapted from DSM-IV.2

OCD sufferers are more likely than comparison subjects to have a per-
sonality disorder, OCPD is present in only a minority of cases, and is less
common than mixed, dependent, avoidant and histrionic personality dis-
orders. For example, in a study of 96 consecutive DSM-III OCD patients,
only 6% fulfilled DSM criteria for OCPD using a standardized diagnostic
instrument.30 These findings indicate that OCPD is not a prerequisite for
the development of OCD. In some cases OCD predates the development
of personality disorders such as OCPD, and some experts have hypothe-
sized that OCPD may develop as an adaptive response to long-standing
OCD of early onset.
Schizophrenia
Distressing obsessions and compulsions affect 10–25% of schizophrenic
patients, and these are often the most severely disabled and challenging
cases. Preliminary findings suggest that the OCD requires separate treat-
ment, since antipsychotic drugs are generally ineffective on their own
and may occasionally make the OCD worse.31
Schizotypal personality disorder (SPD) is thought to be related to
schizophrenia. It occurs in at least 5% of the OCD population, and is
more common in the severely disabled group. Comorbid SPD confers a
poor treatment outcome, and may be a common factor linking the other
psychosocial indicators of poor prognosis including inadequate social
function, poor treatment compliance, and poor insight.30
Somatic manifestations of OCD
One of the most common physical manifestations is dermatitis from

excessive cleaning rituals. A screening of 92 patients attending a derma-
tology clinic by means of the Mini-International Neuropsychiatric Inter-
view22 revealed that approximately 20% scored positive either for OCD or
for a clinically relevant spectrum disorder such as body dysmorphic dis-
order. In most cases the obsessional symptoms had not been previously
diagnosed. Patients suffered from a variety of dermatological problems,
most notably eczema and acne.
The genitourinary clinic is another area frequented by OCD sufferers
with obsessions concerning sexually transmitted disease, nowadays
mainly human immunodeficiency virus (HIV) infection. Patients with
hypochondriacal obsessions present widely to hospital services, seeking
medical reassurance, and their OCD usually escapes notice (Table 1.6).
There is a need for a greater awareness of OCD in non-psychiatric
health-care settings.
Table 1.6 Non-psychiatric health specialists likely to see patients with

OCD.
Specialist Presenting condition
Dermatologist Chapped hands, eczema, trichotillomania, body

dysmorphic disorder
General practitioner Hypochondriasis
Oncologist Fear of cancer
Genitourinary specialist Fear of HIV
Neurologist OCD associated with Tourette’s syndrome
Obstetrician OCD during pregnancy or the puerperium
Gynaecologist Vaginal discomfort from douching
Raising the profile of OCD
Obsessive compulsive disorder is a secretive condition. Most patients

are ashamed and confused by their illness. Many fear they are mad and
actively disguise their symptoms to prevent discovery, and it usually
takes years before they find a health professional in whom they feel they
can confide (see Chapter 14). Untreated OCD is responsible for consid-
erable social impairment and emotional morbidity.
Early recognition and accurate diagnosis are thus important public
health objectives.8 In spite of recent media publicity, lack of education
remains a major problem. Although surveys suggest the time lag
between onset of symptoms and correct diagnosis is shortening,32
patients still wait on average 17 years before appropriate treatment is ini-
tiated.8 Many practitioners are still unfamiliar with OCD and are unable to
recognize or treat it correctly.
Increased awareness is the key to better recognition and treatment of
OCD. Practitioners in areas known to attract high numbers of OCD suffer-
ers should be primed to look for symptoms, and active screening for
OCD using direct enquiry (e.g. Table 1.7) should be routinely incorpo-
rated into every mental state examination.
Table 1.7 Five questions to identify an OCD sufferer.

Do you wash or clean a lot?
Do you check things a lot?
Is there any thought that keeps bothering you that you would like to get rid of but
can’t?
Do your daily activities take a long time to finish?
Are you concerned about orderliness or symmetry?
Reproduced with kind permission of the International Council on OCD. Adapted from International
Council on OCD, Update on OCD (Medical Action Communications: Egham, Surrey, UK 1995).
References
1 World Health Organization, ICD reappraisal, Am J Psychiatry
10 Classification of Mental and (1997) 154:1120–6.
Behavioural Disorders. Clinical 11 Degonda M, Wyss M, Angst J,
Descriptions and Diagnostic The Zurich Study. XVIII. Obses-
Guidelines (WHO: Geneva, 1992). sive compulsive disorders and
2 American Psychiatric Association, syndromes in the general popula-
Diagnostic and Statistical Manual tion, Eur Arch Psychiat Clin Neu-
of Mental Disorders, 4th edn rosci (1993) 243:16–22.
(American Psychiatric Associa- 12 Valleni-Basile LA, Garrison CZ,
tion: Washington, DC, 1994). Jackson KL et al, Frequency of
3 Rasmussen SA, Eisen JL, The obsessive compulsive disorder in
epidemiology and differential a community sample of young
diagnosis of obsessive compul- adolescents, J Am Acad Child
sive disorder, J Clin Psychiatry Adolesc Psych (1994) 33:782–91.
(1992) 53(suppl.):4–10. 13 Riddle MA, Scahill L, King R et al,
4 Hollander E, Benzaquen SD, The Obsessive compulsive disorder in
obsessive-compulsive spectrum children and adolescents. J Am
disorders, Int Rev Psychiatry Acad Child Adolesc Psych (1990)
(1997) 9:99–109. 29:766–72.
5 Robins LN, Holzer JE, Weissman 14 Rasmussen SA, Eisen JL. Epi-
MM et al, Lifetime prevalence of demiology of obsessive compul-
specific psychiatric disorders in sive disorder. J Clin Psychiatry
three sites, Arch Gen Psychiatry (1990) 51(suppl.):10–13.
(1984) 41:949–58. 15 Swedo SE, Rapoport JL, Leonard
6 Myers J, Weissman M, Tischler G H et al, Obsessive compulsive
et al, Six month prevalence of disorder in children and adoles-
psychiatric disorders in three cents: clinical phenomenology of
communities, Arch Gen Psychia- 70 consecutive cases, Arch Gen
try (1984) 41:959–67. Psychiatry (1989) 46:335–41.
7 Weissman MM, Bland RC, Canino 16 Neziroglu F, Anemone R, Yaryura-
GL et al, The cross national epi- Tobias JA, Onset of obsessive
demiology of obsessive- compulsive disorder in preg-
compulsive disorder, J Clin nancy. Am J Psychiatry (1992)
Psychiatry (1994) 55:5–10. 149:947–50.
8 Hollander E, Wong C, Psychoso- 17 Pauls DL, Alsobrook JP, Good-
cial functions and economic costs man W et al, A family study of
of obsessive compulsive disor- obsessive compulsive disorder,
der, CNS Spectrums (1998) Am J Psychiatry (1995) 152:
3(5)suppl. 1:48–58. 76–84.
9 Nelson E, Rice J, Stability of diag- 18 Skoog G, Skoog I, A 40-year
nosis of obsessive-compulsive follow-up of patients with
disorder in the Epidemiological obsessive-compulsive disorder,
Catchment Area Study. Am J Psy- Arch Gen Psychiatry (1999)
chiatry (1997) 154:826–31. 56:121–7.
10 Stein MB, Forde DR, Anderson G 19 Steketee G, Eisen J, Dyck I et al,
et al, Obsessive-compulsive dis- Predictors of course in obsessive
order in the community: an epi- compulsive disorder, Psychiatr
demiological study with clinical Res (1999) 89(3):229–38.
20 Rasmussen SA, Eisen JL, Epi- compulsive disorder, Adv Psych

demiology and clinical features of Treatm (1999) 5:357–65.
obsessive compulsive disorder. 27 Leckman JF, Grice DE, Barr LC et
In: Jenike M, Baer L, Minichiello al, Tic-related vs. non-tic-related
WE, eds, Obsessive Compulsive obsessive compulsive disorder,
Disorders. Theory and Manage- Anxiety (1994–5) 1(5):208–15.
ment (Year Book: Chicago, 1990)
10–27. 28 Eapen V, Robertson MM, Also-
brook JP et al, Obsessive com-
21 Insel T, Akiskal H, Obsessive pulsive symptoms in Gilles de la
compulsive disorder with psy- Tourette syndrome and obsessive
chotic features: a phenomenolog- compulsive disorder: differences
ical analysis, Am J Psychiatry by diagnosis and family history,
(1986) 143:1527–33. Am J Med Genet (1997) 74(4):
22 Sheehan DV, Lecrubier Y, Janavs 432–8.
J et al, Mini-international neu- 29 Alsobrook JP, Leckman JF,
ropsychiatric interview (MINI). Goodman WK et al, Segregation
University of South Florida Insti- analysis of obsessive compulsive
tute for Research in Psychiatry, disorder using symptom-based
Tampa, Fl, USA, and factor scores, Am J Med Genet
INSERM-Hôpital de la Salpetrière, (1999) 88(6):669–75.
Paris, France, 1994.
30 Baer L, Jenike MA, Personality
23 Eisen JL, Rasmussen SA, Obses- disorders in obsessive compul-
sive compulsive disorder with sive disorder, Psychiatr Clin North
psychotic features, J Clin Psychi- Am (1992) 15(4):803–12.
atry (1993) 54(10):373–9.
31 Zohar J, Sasson Y, Chopra M et
24 Swedo S, Rapoport S, Leonard H al, Schizo-obsessive subtype:
et al, Obsessive disorder in chil- obsessions and delusions, CNS
dren and adolescents. Arch Gen Spectrums (1998) 3(5)suppl. 1:
Psychiatry (1989) 46:335–41. 38–9.
25 Hollander E, Greenwald S, Neville 32 Mallery E, The subjective experi-
D et al, Uncomplicated and ence of OCD. A questionnaire
comorbid obsessive compulsive based study from members of the
disorder in an epidemiological self-help organisation ‘Obsessive
sample, CNS Spectrums (1998) Action’. Unpublished oral presenta-
3:(5)suppl. 1; 10–18. tion to the Second Annual Confer-
26 Fineberg N, Evidence-based ence of Obsessive Action, October
pharmacotherapy for obsessive- 1996, Conway Hall, London.
2
Assessment of OCD
Toby D Goldsmith, Nathan A Shapira and Wayne K

Goodman
As in the treatment of other illnesses, the appropriate diagnosis and

assessment of obsessive compulsive disorder is imperative for proper
management. Obsessive compulsive disorder (OCD) is a common psy-
chiatric illness with a lifetime prevalence of 2.5% in the general popula-
tion.1 Because of embarrassment, patients are often reticent to present
for treatment or spontaneously share their OCD symptoms with their
caregiver.
The clinician must first determine if the diagnosis is appropriate. A
thorough diagnostic evaluation is most effective. In addition to a clinical
interview, the clinician may choose to have the patient complete either a
screening tool to help validate the diagnostic evaluation or a rating scale
to evaluate the extent of the symptoms. This information would be used to
establish a baseline level of impairment. This chapter reviews the various
tools that psychiatrists and other mental health professionals may use in
the assessment of their patients.
Diagnostic tools
While face-to-face interviews are necessary for establishing rapport

between patient and practitioner, a differential diagnosis may be initiated
from information gathered during the interview. More structured screen-
ing tools not only further define diagnosis, but may determine the pres-
ence of additional psychiatric disorders from which the patient may
suffer. There are both patient-administered and clinician-administered
diagnostic and screening instruments; it is the clinician’s choice which
format is most useful in the given clinical setting.
The diagnosis of OCD symptoms can be confusing. Symptoms that
appear to be obsessions may actually represent those of another disease
(for example, ruminations in major depression or worries in generalized
anxiety disorder). Tic disorders may be misdiagnosed as compulsions
when the tics are complex, such as repetitive grooming and evening-up.
15
With appropriate training the clinician can learn to make distinctions

between obsessions and compulsions and the other symptoms from
which patients suffer.
Structured Clinical Interview for DSM-IV

The Structured Clinical Interview for DSM-IV (SCID-IV) is among the most
widely used clinician-administered screening tools for OCD.2 Its exten-
sive categorized questions are useful when a complete differential diag-
nosis of Axis I disorders is desired. While completing the SCID-IV is
time-consuming (especially in the presence of multiple diagnoses) the
questions for each diagnosis are succinct, thus allowing for a quick
determination if a particular diagnosis is present.
In university settings, the SCID-IV is generally carried out by a mental
health clinician, such as a licensed psychologist, psychiatrist or social
worker. For accurate diagnosis, the clinician must have appropriate train-
ing in using the SCID-IV. Between appropriately trained individuals, inter-
rater reliability for the diagnosis of OCD is high, with a kappa score of
0.59 for a current diagnosis and 0.67 for a lifetime diagnosis.3
Anxiety Disorders Interview Schedule for DSM-IV

The Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV) is useful
for establishing the presence or absence of psychiatric disorders.4 The
ADIS-IV is anxiety disorder-specific, unlike the SCID-IV; it also evaluates
for highly comorbid diagnoses, such as affective disorders and sub-
stance abuse. For the clinician who requires a thorough assessment for
anxiety disorders, the ADIS-IV is a more appropriate screening instru-
ment than the SCID-IV.5
In the hands of a trained rater, the ADIS-IV may be a more reliable tool
for diagnosing OCD than the SCID-IV, with an interrater reliability kappa
score of 0.75 to 0.80.6 Studies using the SCID-IV were performed differ-
ently from those using the ADIS-IV (multisite versus single site), which
may account for the difference in kappa scores.
Rating instruments
Once the diagnosis of OCD is established, the clinician should determine

the extent and severity of the symptoms. When symptoms are less
severe, treatment may proceed at a more deliberate pace. In the pres-
ence of more significant symptoms and greater disability, the clinician
may wish to approach treatment more aggressively. In addition, the
results of rating tools may be useful in establishing a baseline for the
patient’s symptoms; repeated assessments after treatment has been initi-
Assessment 17
ated may be useful in tracking improvement and other changes, thus

allowing for treatment adjustments. The diagnosis of OCD symptoms may
be difficult. Some symptoms may be apparent only in specific environ-
ments, for example at home or at work. Because of embarrassment and
shame, the patient may confound accurate assessment by concealing
the degree of suffering. Patients may be reticent to share the exact nature
of their obsessions and compulsions. Providing a supportive setting and
ensuring confidentiality will assist in obtaining an accurate picture of the
illness. With appropriate training a clinician can learn to derive an accu-
rate view of the nature and severity of obsessions and compulsions.
Yale–Brown Obsessive Compulsive Scale

Although developed as a measurement tool for symptom severity and
improvement in clinical drug trials, the Yale–Brown Obsessive Compul-
sive Scale (Y–BOCS, see Appendix 1, p. 183) has become the most
widely used tool for assessing symptom severity.7–9 It has been translated
into more than a dozen languages. Unlike other measurement tools, the
number of symptoms does not affect the Y–BOCS score; rather it
assesses the extent to which the symptoms affect the individual’s life.
The Y–BOCS consists of three sections. In the first, the clinician reads
out to the patient descriptions and examples of obsessions and compul-
sions. Section two contains a symptom checklist of obsessions and com-
pulsions; current and previous symptoms are identified during this
section. The third consists of 10 core items and 11 investigational ques-
tions. The core items are rated by the clinician with a five-point scale
(possible scores of 0–4), assessing the extent of symptoms. It is neces-
sary that obsessions and compulsions are differentiated from the rumina-
tions and ideations of other illnesses. The first item for both obsessions
and compulsions defines the amount of time the patient spends on them,
from ‘no time’ to ‘more than 8 hours a day’. Other items review the
patient’s disruption and distress caused by the symptoms, and the resis-
tance and control that are possible over these symptoms.7 There are sep-
arate subtotal scores for both the obsession and compulsion sections.
This allows a quantification of the illness when only one or the other
symptom is present. This is allowable in the DSM-IV criteria for OCD.10
The investigational items for the Y–BOCS evaluate separately avoid-
ance, indecisiveness, insight, pathological responsibility, slowness and
doubting. Two additional questions are based on another inventory, the
Clinical Global Impressions Scale.11 A final item assesses the clinician’s
assessment of the reliability of the patient’s report of symptoms. Investi-
gational items are not added to the final Y–BOCS score of the core items.
When administering the Y–BOCS, it may be necessary to define obses-
sions and compulsions in terms of the patient’s knowledge and
understanding. During the second part of the evaluation, the patient is
asked to specify both current and past obsessions and compulsions.

These are based on the Y–BOCS symptom checklist; previous symptoms
may resurface during treatment. Patient and clinician then describe the
particular symptoms on the Y–BOCS target symptom list; those that are
the most disturbing to the patient should be defined. Avoidance of cer-
tain situations is also recorded, since some patients limit their anxiety by
shunning circumstances that evoke negative thoughts or feelings. Finally,
the patient is asked to respond to the 19 core and investigational items;
there may be circumstances when collateral information may be required
to appropriately assess symptom severity (as in the case of children, or
patients with little insight).
The Y–BOCS has been well studied and found to be a reliable instru-
ment for determining symptom severity. Researchers have found it to
have excellent interrater reliability and admirable test–retest reliability.12–14
The Y–BOCS has also been found to be a good assessment tool for mon-
itoring change in symptoms.15–17 Changes in symptoms monitored by the
Y–BOCS were specific for OCD and not for other anxiety disorders or
depression.8 Given the extent of validating research, clinicians can confi-
dently use the Y–BOCS to assess the scope of their patients’ illness.
The Y–BOCS has been modified into patient-administered screening
tools. A computerized version may be used either in an office setting or
administered by telephone.18,19 Studies using both of these versions have
found the tests to be consistent with clinician-administered versions of
the Y–BOCS; normal control subjects, however, were noted to rate their
symptoms as more significant than the trained raters, so this tool may not
be appropriate for large-scale screening. However, it could be appropri-
ately used for follow-up after a clinician-rated Y–BOCS has been adminis-
tered. Two pen-and-paper forms have been developed as well, the
Screening Test for Obsessive-compulsive Problems (STOP) for
community-based settings and the Florida Obsessive Compulsive Inven-
tory (FOCI) for clinics. Both consist of two parts determining the presence
of symptoms, and the severity of these symptoms. The FOCI has more
questions than the STOP and thus takes more time to administer. Little
controlled data are available on either of these tests.
Maudsley Obsessional Compulsive Inventory

A 30-item true–false test, the Maudsley Obsessional Compulsive Inven-
tory (MOCI, see Appendix 1, p. 216) was developed as a research tool to
elucidate symptoms in previously diagnosed OCD patients.20 The MOCI
was derived from a larger set of items; this subset of the questions was
determined to differentiate between patients with OCD and non-
psychotic patients without OCD. There are four principal groups of OCD
symptoms assessed by the MOCI: ‘checking’, ‘cleaning’, ‘slowness’, and
‘doubting’. Each group can be scored individually. Unfortunately, OCD
Assessment 19
symptoms such as hoarding and aggression obsessions are not well

examined by the MOCI. Given that the severity of symptoms is not
scored, patients who have several symptoms will score higher than those
with one or two symptoms even if both are equally disabled by the disor-
der. The MOCI has been found to be reliable and valid,20 and in clinical
drug trials it has been shown to detect symptom improvement, with small
but significant changes from the baseline MOCI score.21,22 This test is
brief and easy to administer; however, it is limited in its scope of OCD
symptoms and may not detect changes or improvement in symptoms.
Leyton Obsessional Inventory

The Leyton Obsessional Inventory (LOI) was used extensively prior to the
introduction of the Y–BOCS.23,24 This 69-question test can be used to
assess obsessionality. For the clinician, the pen-and-paper version is the
less cumbersome to administer. The LOI evaluates obsessional thoughts,
although thoughts that are of a violent or other unacceptable nature are
evaluated in less detail. The thoughts are scored in a dichotomous way.
The level of resistance and interference with other activities are evaluated
on a scale of 0–3 to help differentiate patients from those without
OCD. An increased level of subjective disturbance is associated with a
higher score. There are questions about the validity of the LOI.25,26 It has
not been found to be a consistent instrument for evaluating change in
symptoms compared with other tools,27,28 and thus the LOI may be less
useful to the clinician in practice.
Padua Inventory
The Padua Inventory (PI), developed in 1988, was designed to improve the
measurement of obsessive compulsive symptoms.29 Its validity and reliabil-
ity were tested on healthy volunteers and therefore its use in OCD is
questionable. The revised version (PI-R), a 41-item tool, has been evalu-
ated in OCD patients.30 The 41 questions of the PI-R are divided into five
sections: ‘impulses’, ‘washing’, ‘checking’, ‘rumination’ and ‘precision’. This
tool has been found to be reliable and consistent. The weakness of the
PI-R lies in its inability to differentiate between obsessions and worries.31
Further modifications of the PI have rectified this problem to an extent,32 yet
it may not completely differentiate OCD from depression or other anxiety
disorders.
Conclusion
For the fastidious clinician, a diagnostic interview may only be the begin-
ning of the evaluation process for OCD. A variety of assessment tools are
used by researchers to elucidate the diagnosis and clarify the effects of

treatment, and for the most part the statistical reliability and validity of
these tools have been well established. Others may not be as sensitive or
specific to the diagnosis of OCD, leading to the confusion of obsessions
and compulsions with different psychiatric symptoms. For the clinician
who wishes to administer testing for OCD, training in the administration
and interpretation of these tools is essential. Well-educated clinicians
may be pleased with the impact such training will have on their practice
and their patients.
References
1 Robins LN, Helzer JE, Weissman 7 Goodman WK, Price LH, Ras-
MM et al, Lifetime prevalence of mussen SA et al, The Yale–Brown
specific psychiatric disorders in Obsessive-Compulsive Scale. I.
three sites, Arch Gen Psychiatry Development, use and reliability,
(1984) 41:949–58. Arch Gen Psychiatry (1989)
2 First MB, Spitzer RL, Gibbon M, 46(11):1006–11.
Williams JBW, Structured Clinical 8 Goodman WK, Price LH, Ras-
Interview for DSM-IV Axis I Disor- mussen SA et al, The Yale–Brown
ders – Patient edition (SCID-I/P, Obsessive-Compulsive Scale. II.
Version 2.0) (Biometrics Research Validity, Arch Gen Psychiatry
Department, New York Psychi- (1989) 46(11):1012–16.
atric Institute: New York, 1996).
9 Goodman WK, Rasmussen SA,
3 Williams JB, Gibbon M, First MB et Price LH, Mazure C, Heninger
al, The Structured Clinical Interview GR, Charney DS, Manual for the
for DSM-III-R (SCID): II. Multisite Yale–Brown Obsessive Scale
test-retest reliability, Arch Gen (revised) (Connecticut Mental
Psychiatry (1992) 49:630–6. Health Center: New Haven,
4 DiNardo P, Brown K, Barlow DH, 1989).
Anxiety Disorders Interview 10 American Psychiatric Association,
Schedule for DSM-IV (Psychologi- Diagnostic and Statistical Manual
cal Corporation: San Antonio, of Mental Disorders, 4th edn
1994). (American Psychiatric Press:
5 Taylor S, Assessment of Washington, DC, 1994).
obsessive compulsive disorder.
11 Guy W, ECDEU Assessment Man-
In: Swinson RP, Antony WM,
ual for Psychopharmacology,
Rachman S, Richter MA, eds,
publication no. 76-338 (US
Obsessive Compulsive Disorder:
Department of Health, Education
Theory, Research and Treatment
and Welfare: Washington, DC,
(Guilford Press: New York, 1998)
229–57. 1976).
6 DiNardo P, Moras K, Barlow DH, 12 Kim SW, Dysken MW, Katz R, The
Rapee RM, Brown TA, Reliability Yale–Brown Obsessive-Compulsive
of DSM-III-R anxiety disorders Scale: a reliability and validity
categories: using the Anxiety Dis- study. Psychiatr Res (1990) 34:
orders Interview Schedule- 99–106.
Revised (ADIS-R), Arch Gen 13 Kim SW, Dysken MW, Kuskowski
Psychiatry (1993) 50:251–6. MA, Hoover KM, The Yale–Brown
Assessment 21
obsessive compulsive scale (Y- Arch Gen Psychiatry (1989)

BOCS) and the NIMH global 46(1):36–44.
obsessive-compulsive scale 22 Perse TL, Greist JH, Jefferson
(NIMH-GOCS): a reliability and JW, Rosenfeld R, Dar R, Fluvox-
validity study, Int J Meth Psychiatr amine treatment of obsessive
Res (1993) 3:37–44. compulsive disorder, Am J Psy-
14 Woody SR, Steketee G, Chamb- chiatry (1987) 144:1543–8.
less DL, Reliability, and validity of 23 Cooper J, The Leyton obsessional
the Yale–Brown Obsessive- inventory, Psychol Med (1970)
Compulsive Scale. Behav Res 1(1):48–64.
Ther (1995) 33:597–605.
24 Snowdon J, A comparison of writ-
15 Clomipramine Collaborative Study ten and postbox forms of the Ley-
Group, Clomipramine in the treat- ton Obsessional Inventory,
ment of patients with obsessive Psychol Med (1980) 10:165–70.
compulsive disorder, Arch Gen 25 Clark DA, Bolton D, An investiga-
Psychiatry (1991) 48:730–8. tion of two self report measures of
16 Tollefson GD, Rampey AH, Potvin obsessional phenomena in
JH et al, A multicenter investiga- obsessive-compulsive adoles-
tion of fixed-dose fluoxetine in the cents. Research note, J Child Psy-
treatment of obsessive compul- chol Psychiatry (1985) 26:429–37.
sive disorder, Arch Gen Psychia- 26 Philpott R, Recent advances in
try (1994) 51(7):559–67. the behavioural measurement of
17 Wheadon DE, Bushnell WD, obsessional illness. Difficulties
Steiner M, A fixed dose compari- common to these and other
son of 20, 40 or 60 mg Paroxetine instruments, Scott Med J (1975)
to placebo in the treatment of 20:33–40.
obsessive compulsive disorder 27 Insel TR, Murphy DL, Cohen RM,
[abstract]. (ACNP: Hawaii, 1993). Alterman I, Kilts C, Linnoila M,
18 Baer L, Brown-Beasely MW, Obsessive compulsive disorder: a
Sorce J, Henriques A, Computer- double-blind trial of Clomipramine
assisted telephone administration and clorgyline, Arch Gen Psychi-
of a structured interview for atry (1983) 40:605–12.
obsessive compulsive disorder, 28 Thoren P, Asberg M, Cronholm B
Am J Psychiatry (1993) 150: et al, Clomipramine treatment of
1737–8. obsessive compulsive disorder I:
19 Rosenfeld R, Dar R, Anderson D, a controlled clinical trial, Arch
Koback KA, Greist JH, A Gen Psychiatry (1980) 37:1281–5.
computer-administered version of 29 Sanavio E, Obsessions and com-
the Yale–Brown Obsessive- pulsions: the Padua Inventory,
Compulsive Scale, Psychol Behav Res Ther (1988) 28:
Assess (1992) 4:329–32. 314–45.
20 Hodgson RJ, Rachman S, 30 Van Oppen P, Hoekstra RJ,
Obsessional-compulsive com- Emmelkamp PMG, The structure
plaints, Behav Res Ther (1977) of obsessive-compulsive symp-
15:389–95. toms, Behav Res Ther (1995) 33:
21 Goodman WK, Price LH, Ras- 15–23.
mussen SA, Delgado PL, 31 Freestone MH, Ladouceur R,
Heninger GR, Charney DS, Effi- Rheaume J, Letarte H, Gagnon F,
cacy of fluvoxamine in obsessive Thibodeau N, Self-report of
compulsive disorder. A double- obsessions and worry, Behav Res
blind comparison with placebo, Ther (1994) 32:29–36.
32 Burns GL, Keortge SG, Formea distinctions between worry,

GM, Sternberger LG, Revision of obsessions and compulsions,
the Padua Inventory for obsessive Behav Res Ther (1996) 34:
compulsive disorder symptoms: 163–73.
3
Obsessive compulsive spectrum disorders:
from serotonin to dopamine and back again
Michael Van Ameringen, Jonathan M Oakman,

Catherine Mancini and Peter Farvolden
A variety of similarities have been observed among a number of psychi-

atric and neuropsychiatric conditions and obsessive compulsive disorder
(OCD). Some researchers suggest that this wide range of disorders
shares enough similar features with OCD to be meaningfully grouped
with it. The set of candidate disorders includes: somatoform disorders
such as somatization disorder, hypochondriasis and body dysmorphic
disorder; eating disorders (anorexia nervosa, bulimia nervosa, binge eat-
ing disorder); impulse control disorders such as problem gambling, klep-
tomania, compulsive buying, and trichotillomania; the paraphilias and
non-paraphilic sexual addictions; Axis II disorders such as borderline
and obsessive compulsive personality disorder; onychophagia (severe
nail-biting), psychogenic excoriation (compulsive skin-picking) and
repetitive self-mutilation. The list may also include disorders such as
Tourette’s syndrome, autism and Asperger’s syndrome, and neurological
conditions such as Sydenham’s chorea. This group of disorders has
been collectively referred to as the obsessive compulsive (OC) spectrum
of disorders.1–3 One common feature of these conceptual schemes is that
OCD is thought to be the prototype for this group of disorders.
While many researchers seem to share the opinion that OCD is the
prototype disorder of the OC spectrum, the disorder itself defies proto-
typal characterization. The presentation of OCD is heterogeneous; there
is little to suggest a set of common elements and at least some evidence
to suggest that there may be several different prototypes. These diverse
presentations may be clinically discrete, being based on different neu-
ropsychological substrates and having different treatment responses.
Furthermore, these different types of OCD may be co-transmitted with dif-
ferent putative spectrum disorders. Hollander and Wong suggest a sub-
division of OCD into five subtypes:
1. an obsessive compulsive personality subtype
2. an obsessional slowness subtype
23
3. a poor insight subtype

4. a harm-avoidant, adult-onset, non-tic-related subtype
5. a symmetry, childhood-onset, ‘just so’, tic-related subtype.
An alternative system of three subtypes derives from the factor analytic
work of Baer:4
1. ‘symmetry/hoarding’ (impulsions)
2. ‘contamination/cleaning’ (compulsions)
3. ‘pure obsessions’.
To the extent that the subtypes proposed in either of these systems rep-
resent meaningful categories of OCD, it may be more appealing to think
in terms of multiple spectra of OCD, rather than a single unified OCD
spectrum.
Conceptualizations of the OCD spectrum

There are a number of different conceptualizations of the OC spectrum.5–8
Jarry and Vaccarino proposed that OCD and eating disorders are con-
nected by an approach/avoidance continuum.6 The contamination con-
cerns of OCD and the restricting behaviour of anorexia are characterized
by excessive avoidance. The sexual and violent obsessions of OCD and
the gorging of bulimia are characterized by excessive approach. Alterna-
tively, Hollander and Rosen proposed a dimension of compulsivity and
impulsivity to explain a subset of the OCD spectrum, with OCD and body
dysmorphic disorder at the compulsive end, and borderline and anti-
social personality disorders at the impulsive end.5 Hollander and Rosen
suggest that the compulsive end of the dimensions is characterized by
harm overestimation, while the impulsive end is characterized by under-
estimation of harm. Similarly, McElroy, Phillips and Keck argue that the
OCD spectrum disorders are unified by a common core of compulsivity
and/or impulsivity.7 They argue for broadening the OCD spectrum to
include all conditions characterized by obsessional thinking or behav-
ioural stereotypies. In contrast, Rasmussen cautions that such an inclu-
sive scheme may be unwarranted; many of the putative OCD spectrum
disorders may be unrelated to OCD, and OCD itself may be a hetero-
geneous set of illnesses.8,9 Rasmussen argues that there may be three
core features of OCD, including abnormal risk assessment, pathological
doubt, and incompleteness, and that these core features connect with
some of the OCD spectrum disorders. Abnormal risk assessment is often
comorbid with other obsessional illnesses such as generalized anxiety
disorder or social phobia, while incompleteness is often comorbid with
tics or habit disorders such as trichotillomania.
There is better evidence for the grouping of some of the OCD spec-
Obsessive compulsive spectrum disorders 25
trum disorders with OCD and with each other than for others. For exam-
ple, Bienvenu et al conducted a family study of OCD and found that body
dysmorphic disorder may be co-transmitted with OCD, while the evi-
dence was considerably weaker for other disorders.10 Similarly, the evi-
dence concerning the association of obsessive compulsive personality
disorder with OCD is very weak.11–13 It is possible that in our zeal to group
similar disorders we have been overinclusive. It stretches a point to
argue that all disorders that involve repetitive behaviour, intrusive
thoughts and behaviour that is experienced as ‘compelled’ are all some-
how related to OCD. Some have argued that most psychopathological
conditions and a great deal of normal behaviour involves some degree of
stereotypy, if stereotypy is broadly construed.2
The tic-related subtype of OCD and related disorders
While much of the current theorizing about OC spectrum disorders is

speculative, there is substantial evidence that suggests an important
relationship between OCD and tic disorders, including Tourette’s syn-
drome.14 At present the clearest distinction to be made among subtypes
of OCD is the distinction between tic-related and non-tic-related OCD. In
this chapter we will focus on tic-related OCD and the disorders that may
go with it. We group some spectrum disorders with tic-related OCD partly
on the basis of phenomenology and comorbidity, but in doing so we pro-
pose a dimension that describes the relationship between OCD and
some of the other potential OC spectrum disorders that goes beyond
simple descriptive similarities and has implications for treatment.
Tourette’s syndrome (TS) is characterized by motor tics and one or
more vocal tics beginning before the age of 18 years.15 The tics of TS can
share some phenomenological similarities with the compulsions of
OCD.16,17 People with TS report that while they can delay their tics, they
find them irresistible, experience relief when they perform them, and
sometimes need to perform them until they are ‘just right’.17 People with
TS also report experiencing sensory phenomena prior to or concomitant
with their tics that can resemble OCD obsessions, and that their tics are
exacerbated by stress.16 Obsessive compulsive disorder and OCD
symptoms are common in patients with TS, with observed rates ranging
from 12% to 90%,16,17 and patients with OCD have been found to have
high rates (37–59%) of tics and tic disorders.18,19
The most striking similarity between TS and OCD is that both are char-
acterized by repetitive behaviour that is apparently senseless. Consider-
able attention has recently been turned to the task of classifying
repetitive behaviours or stereotypies in terms of subjective experi-
ence.4,20,21 The compulsions typical of OCD are defined in DSM-IV as
‘repetitive behaviors . . . or mental acts . . . the goal of which is to prevent
or reduce anxiety or distress, not to provide pleasure or gratification’.15

Somewhat unlike classic compulsions are ‘impulsions’, which are sponta-
neous actions usually precipitated by a sensation or an urge and which
are performed until a sense of ‘rightness’ or satisfaction is achieved.22
Impulsions are not intended to neutralize an event or obsession but
rather are intended to achieve a sense of completion, relief or satisfac-
tion. Finally, there are tics. Tics may be simple or complex, and may be
experienced as completely involuntary spontaneous muscle twitches or
spasms, or as unvoluntary – based on an urge or sensation that is
relieved by the tic.
According to the conceptual scheme outlined above, some classic
OCD symptoms are impulsions, and others are compulsions. Checking
behaviour would be a compulsion, as it reduces the anxiety brought on
by an obsessive thought. Symmetry, hoarding and repeating would be
impulsions, as they are typically performed until a sense of rightness is
achieved.
Miguel and his colleagues compared three groups of patients: a group
with OCD without tics or TS, a group of TS patients without OCD, and a
group of patients with both OCD and TS.14,20 They found that for OCD
patients without comorbid tics or TS, repetitive behaviour was preceded by
cognitive phenomena (obsessive thoughts or images) and anxiety, but
largely not by sensory phenomena. In contrast, the TS group and the group
with OCD and comorbid TS reported more sensory phenomena and fewer
cognitions than the OCD group. These results support earlier findings by
George et al, who found that patients with both OCD and comorbid TS
reported that their repetitive behaviour arose spontaneously, while patients
with OCD alone reported cognitions preceding repetitive behaviour.23 Fur-
thermore, Rasmussen and Eisen noted that OCD patients with primary con-
cerns about symmetry (an impulsion) reported a feeling of discontent or
tension rather than the experience of anxiety.24
Obsessive compulsive disorder with comorbid tics also seems to
respond differently to treatment compared with more compulsive
OCD. Antidepressants that target serotonergic systems are effective in
the treatment of OCD,25–27 while neuroleptics alone are ineffective.28 In
contrast, TS does not respond to antiobsessional drugs such as
clomipramine and fluoxetine, but does respond to neuroleptic medica-
tion.22,29–31 Moreover, there is a growing body of research evidence sug-
gesting that OCD with comorbid tics is less responsive to serotonin
reuptake inhibiting (SRI) drugs alone, but does respond better to a com-
bination of SRIs and neuroleptic medication.32,33 Case studies and open
trials (for example that of McDougle et al,32 reviewed by Goodman et al28
have been followed by a controlled investigation of neuroleptic augmen-
tation of SRIs.33 The results of these investigations persuaded McDougle
et al, among others, to argue that OCD with comorbid tics is a clinically
meaningful subtype of OCD.33
If we think of the phenomenology of impulsions and tics as being

related to dopaminergic systems and the phenomenology of obsessions
and compulsions as being more serotonergic, then other disorders that
share this phenomenology may be characterized in this way. Putative
spectrum disorders that have an obsessive phenomenology should be
more related to classic obsessional OCD than to tic-related OCD, and
should respond well to SRI treatment. Disorders that have a tic-like phe-
nomenology, or for which the main symptoms are impulsions, should be
more associated with tic-related OCD and dopamine antagonists may
provide useful treatment augmentation. A prime example of a disorder
that is described by sufferers as like an impulsion is trichotillomania.
Trichotillomania is categorized as an impulse control disorder in
DSM-IV.15 The cardinal symptoms of the disorder are pulling out one’s
hair, resulting in noticeable hair loss; an increasing subjective sense of
tension immediately preceding pulling out the hair or when attempting to
inhibit the desire; and a resulting feeling of relief, gratification or pleasure
when pulling out the hair. Trichotillomania is often considered to be part
of the OC spectrum.34
Considering the symptom-based subtyping of OCD proposed by Baer,4
the hair-pulling behaviour in trichotillomania would be an impulsion, as hair-
pulling is typically not preceded by an obsessive thought but by an urge to
pull,35 and is followed by tension relief.36 Hair-pulling is an end in itself, and
does not serve to reduce anxiety.36 Phenomenologically, trichotillomania
seems more like TS or ‘impulsive’ OCD than classic ‘compulsive’ OCD.
Published evidence is equivocal on the efficacy of fluoxetine and other
SRIs in the treatment of trichotillomania (for a review see Yanchick et
al).37 Swedo and her colleagues conducted a double-blind, crossover
comparison of the treatment of trichotillomania in children with
clomipramine and desipramine, finding that clomipramine treatment
resulted in greater symptom reduction and overall improvement than
desipramine.38 Despite these promising initial results, effective treatment
of trichotillomania with SRIs has not replicated well.39–41
Treating trichotillomania with medications typically used in the treat-
ment of OCD has been largely unsuccessful, or at least much less suc-
cessful than the treatment of OCD with these medications. A number of
researchers have reported promising results with augmentation of SRI
agents with a variety of dopaminergic agents including pimozide (a
dopamine antagonist),35 risperidone,40 and haloperidol.42 Finally, Ninan et
al reported significant therapeutic benefit in an open trial of venlafaxine in
trichotillomania; they argued that the benefit observed was probably due
to venlafaxine’s powerful inhibition of norepinephrine (noradrenaline) as
well as serotonin reuptake.43 However, it is interesting to note that one of
the secondary binding properties of venlafaxine is on dopamine reup-
take.44 In summary, there is now considerable evidence for a role for
dopaminergic agents in the treatment of trichotillomania.
It may be useful to think of at least some OC spectrum disorders as

falling on a continuum anchored by two poles, with classic ‘compulsive’
OCD at one end, and with TS and attendant tic behaviour at the other.
Trichotillomania may be thought of as closer to TS than to OCD on this
tentative axis. The continuum we propose is only one dimension,
accounting for a small subset of the OCD spectrum disorders. Classic
compulsive OCD may be relatively serotonergic, while tic-related OCD
may have an additional dopaminergic influence and may go with trichotil-
lomania, skin-picking, nail-biting and TS. Phenomenologically speaking,
the dimension seems to range from compulsive behaviour to tics, with
impulsions being in between (Figure 3.1). The implication for the treat-
ment is that there is likely to be some promise for dopaminergic agents in
the treatment of disorders such as trichotillomania, skin-picking and nail-
biting.
Clearly, serotonergic systems are important in OCD and the OC spec-
trum disorders. A variety of evidence, apart from treatment response and
the results of pharmacological challenge studies, supports an important
role for serotonin (5-HT) systems in the pathogenesis of OC spectrum
disorders. For example, serotonergic projections from raphe to limbic
structures are involved in anxiety and panic.44 However, current evidence
suggests an important role for other neurotransmitters as well. The fact
remains that only 50–60% of patients with OCD demonstrate a decrease
in OCD symptoms after long-term treatment with an SRI.2 While there may
be evidence for a role for norepinephrine, opioid and hormonal systems
in some of the OC spectrum disorders, the best evidence points to a cen-
trally important role for dopamine in the OC spectrum.33
Dopamine and the OC spectrum
There are four well-defined dopamine pathways in the brain: the nigrostri-
atal, mesolimbic, mesocortical, and tuberoinfundibular pathways (Figure
3.2).44 One way to move towards a better understanding of the OC spec-
trum disorders may be found in research that examines the functioning of
these pathways across various disorders.
OCD Trichotillomania Tic disorders

BDD Skin-picking Putamen
Caudate Nail-biting Dopamine
Serotonin
Figure 3.1
Trichotillomania and the obsessive compulsive spectrum. BDD, body dysmorphic disorder;
OCD, obsessive compulsive disorder.
basal ganglia
nucleus accumbens
1
2
substantia nigra
3
limbic cortex
tegmentum
4
hypothalamus
Figure 3.2
Dopamine pathways in the brain: 1, nigrostriatal; 2, mesolimbic; 3, mesocortical; 4,
tuberoinfundibular.
The nigrostriatal dopamine pathway is a part of the extrapyramidal

motor system and controls motor movements. This pathway projects from
dopaminergic cell bodies in the substantia nigra of the brainstem via
axons terminating in the basal ganglia.44 The basal ganglia are com-
posed of a set of intimately connected structures that include the cau-
date and putamen (striatum), globus pallidus, substantia nigra and
subthalamic nucleus. Approximately 80% of all synapses in the striatum
are cortical inputs. The cortical areas projecting to the striatum can be
roughly divided into ‘motor’ areas, which include somatosensory, motor
and premotor cortices, and ‘limbic associative’ areas, which include
amygdala, hippocampus, and orbital, entorhinal, temporal, prefrontal,
parietal, cingulate and association cortex. A similar level of division can
be maintained at the level of the striatum, with a ‘motor’ putamen and a
‘limbic’ caudate and ventral striatum (nucleus accumbens).45
While Tourette’s syndrome is most often associated with dysfunction of
the putamen, OCD is most often associated with dysfunction of the cau-
date.46 Indeed, it seems likely that involvement of the ventromedial cau-
date nucleus, receiving projections from the anterior orbitofrontal cortex,
leads to the affectively tinged cognitive symptoms of OCD, whereas
involvement of the putamen, receiving projections from sensorimotor cor-
tices, leads to the somatosensory premonitory symptoms and tics of TS.47
It is interesting to note that morphometric magnetic resonance imaging
studies suggest that patients with trichotillomania exhibit subtle volumet-
ric abnormalities of the putamen, as do patients with TS.48 It may be that
skin-picking and onychophagia (severe nail-biting) will also be found to

be associated with relatively more dopaminergic (nigrostriatal) and puta-
men dysfunction.
The mesolimbic dopamine pathway projects from dopaminergic cell
bodies in the ventral tegmental area of the brainstem to axon terminals in
the limbic area of the brain, such as the nucleus accumbens. The
nucleus accumbens is thought to be involved in many behaviours includ-
ing pleasurable sensations, the powerful euphoria of drugs of abuse, as
well as the delusions and hallucinations of psychosis.44 Obsessive com-
pulsive disorder with psychotic features or OC spectrum disorders that
are characterized by delusional obsessions, as is sometimes observed in
somatization disorder, hypochondriasis and the eating disorders,49 may
be associated with dysfunction of the mesolimbic system.
Stimulation of mesolimbic structures, especially the ventral tegmentum,
leads to an immediate and sustained increase in extracellular dopamine
in the nucleus accumbens. This increase in dopamine levels is thought to
be the physiologic correlate of reward. Indeed, the mesolimbic dopamine
pathway and nucleus accumbens appear to be the final common path-
way for the positive reinforcement of a number of survival behaviours
such as eating, drinking and copulation, as well as that of addictive
drugs.50
Obsessive compulsive spectrum disorders including problem gam-
bling,51 compulsive buying, compulsive sexual behaviour, and perhaps
bulimia nervosa, could be viewed as addictive disorders in which the
mesolimbic dopamine pathway is dysfunctional. However, there is more
to addictive behaviour than dopamine and the nucleus accumbens.
There is considerable interest in the role of affect regulation in maintain-
ing addictive behaviours and it seems likely that serotonergic and nor-
adrenergic mechanisms play an important part in these processes.52 In
addition, serotonin and glutamate seem to share a role in the plasticity of
sensitization and learning addictive behaviours, and norepinephrine
seems to be related to risk-taking that crosses diagnostic boundaries.50
Cell bodies for the mesocortical dopamine pathway arise in the ventral
tegmental area of the brainstem and project to various areas of the cere-
bral cortex, especially the limbic cortex. Some researchers believe that
the negative and cognitive symptoms of schizophrenia are due to a
deficit of dopamine to mesocortical projection areas, such as the dorso-
lateral prefrontal cortex.44,53 Relatively non-specific symptoms that may or
may not be present across the OC spectrum disorders and may be asso-
ciated with mesolimbic dopamine pathway dysfunction include cognitive
impairment, attentional problems, affective flattening, poverty of speech,
psychomotor retardation and hoarding.47,53,54
Tuberoinfundibular pathway dopamine neurons project from the hypo-
thalamus to the anterior pituitary.44 Increased prolactin levels are associ-
ated with increased grooming and sexual behaviour.55 Thus, OC
spectrum disorders associated with tuberoinfundibular dopamine path-

way may include trichotillomania, skin-picking, onychophagia, and per-
haps compulsive sexual behaviour.
. . . and back to serotonin again
Rauch and Savage have proposed a model of the functional anatomy

and organization of corticostriatal pathways in which they distinguish
between sensorimotor, oculomotor, dorsal cognitive, ventral cognitive
and affective-motivational corticostriatal circuits (Figure 3.3).46 The
sensorimotor circuit projects from primary and associated sensorimotor
cortex via the putamen, to the ventral tier nuclei of the thalamus. The ocu-
lomotor circuit projects primarily from frontal eye fields via the body of the
caudate nucleus, to the ventral anterior and medial dorsal nuclei of the
thalamus, and plays a part in eye movements. The dorsal cognitive cir-
cuit projects primarily from the dorsal, anterior and lateral regions of the
prefrontal cortex via the dorsolateral portion of the head of the caudate
nucleus to the ventral anterior and medial dorsal nuclei of the thalamus.
The dorsal cognitive circuit is thought to have a role in cognitive
processes including working memory and the ability to establish and shift
mental sets. The ventral cognitive circuit projects from the anterior and
Cortex Striatum Thalamus
sensorimotor
PUTAMEN ventral tier nuclei
medial dorsal nuclei

frontal eye fields
CAUDATE
dorsolateral
lateral prefrontal body anterior nuclei
anterior and lateral ventromedial

orbitofrontal
paralimbic NUCLEUS ACCUMBENS
Circuits ⫽ sensorimotor ⫽ oculomotor ⫽ dorsal cognitive

⫽ ventral cognitive ⫽ affective/motivational
Figure 3.3
Functional anatomy and organization of corticostriatal pathways.
lateral orbitofrontal cortex via the ventromedial portion of the caudate

nucleus, as well as to the ventral anterior and medial dorsal nuclei of the
thalamus, and has an important role in cognitive processes such as
response inhibition, especially as related to social or emotional subject
matter. The affective-motivational circuit projects from paralimbic cortical
territories (i.e. the posteromedial orbitofrontal cortex and the anterior cin-
gulate) via the nucleus accumbens (i.e. the ventral striatum) to the medial
dorsal nucleus within the thalamus. This circuit is also influenced heavily
by limbic structures, such as the amygdala, and has a role in emotional
or reward-based information processing.
An assumption that a model of functional anatomy and organization of
corticostriatal pathways such as that proposed by Rauch and Savage is
roughly accurate provides one reasonable way to further understand the
relationship between such circuits and the OC spectrum disorders. For
example, it may be that certain of the circuits (e.g. sensorimotor, oculo-
motor and affective-motivational circuits) are more vulnerable to
dopaminergic dysfunction, while other circuits (e.g. dorsal and ventral
cognitive circuits) are more dependent on serotonergic functioning.
Clearly, serotonergic dysfunction is important in the pathogenesis of
OCD and many OC spectrum disorders. However, there is evidently
more to OCD and OC spectrum disorders than serotonergic dysfunction
alone. Symptoms of obsessions and compulsive washing, checking and
cleaning are probably associated with functional changes in the caudate
and orbitofrontal cortex as well as dysregulation of serotonergic function-
ing, and this is also likely to be true of OC spectrum disorders such as
body dysmorphic disorder and perhaps hypochondriasis. In contrast,
Tourette’s syndrome is associated with functional changes in the puta-
men and dysregulation of dopaminergic functioning. ‘Impulsive’ OC
spectrum disorders such as trichotillomania and perhaps skin-picking
and onychophagia seem much more like TS than OCD. In this view
patients with OCD and comorbid tics are likely to have functional
changes in caudate, putamen and orbitofrontal cortex, and dysregulation
in both serotonergic and dopaminergic systems.
One road towards a better understanding of the OC spectrum disor-
ders may be found in research that examines the functioning of various
serotoninergic, dopaminergic and noradrenergic pathways and the func-
tional anatomy and organization of corticostriatal pathways across vari-
ous disorders.47 For example, it seems likely that dopamine
(approach/reward), serotonin (learning, mood, impulsivity), norepineph-
rine (risk-taking) and the opiate system all have a role in the initiation and
maintenance of addictive behaviours and perhaps some ‘addiction-like’
OC spectrum disorders including problem gambling, compulsive buying,
compulsive sexual behaviour, and perhaps bulimia nervosa.
While the outline of a potential understanding of the variety of putative
OC spectrum disorders presented here has been brief, we hope it
encourages the interested clinician to think beyond the ‘chicken bones’

of patterns of comorbidity. Certainly the field needs more clinicians and
researchers who are willing to move towards testable models of the OC
spectrum based on consideration of ethology, neurobiology and treat-
ment response.2,47
References
1 Hollander E, Wong CM, Spec- Obsessive compulsive spectrum
trum, boundary, and subtyping disorder, J Clin Psychiatry (1994)
issues: implications for treatment- 55(suppl.):33–51.
refractory obsessive-compulsive 8 Rasmussen SA, Obsessive com-
disorder. In: Goodman WK, pulsive spectrum disorders, J Clin
Rudorfer MV, Magser J, eds, Psychiatry (1994) 55(3):89–91.
Obsessive-Compulsive Disorder:
Contemporary Issues in Treat- 9 Rasmussen S, Eisen JL, The epi-
ment (Lawrence Erlbaum: Mah- demiology and differential diag-
wah, 2000). nosis of obsessive compulsive
disorder, J Clin Psychiatry (1994)
2 Stein DJ, Advances in the neuro- 55(suppl.):5–10.
biology of obsessive-compulsive
disorder: implications for concep- 10 Bienvenu OJ, Samuels JF, Riddle
tualizing putative obsessive- MA et al, The relationship of
compulsive and spectrum obsessive-compulsive disorder to
disorders, Psychiatr Clin North possible spectrum disorders:
Am (2000) 23(3):545–61. results from a family study, Biol
Psychiatry (2000) 48:287–93.
3 Goldsmith T, Shapira NA, Phillips
11 Rosen KV, Tallis F, Investigation
KA, McElroy SL, Conceptual foun-
into the relationship between per-
dations of obsessive-compulsive
sonality traits and OCD, Behav
spectrum disorders. In: Swinson
Res Ther (1995) 33(4):445–50.
RP, Antony MM, Rachman S,
Richter MA, eds, Obsessive-Com- 12 Black DW, Noyes R, Pfohl B, Gold-
pulsive Disorder: Theory, stein RB, Blum N, Personality disor-
Research and Treatment (Guilford ders in OCD volunteers, well-
Press: New York, 1998). comparison subjects, and their first
degree relatives, Am J Psychiatry
4 Baer L, Factor analysis of symp-
(1993) 150(8):1226–32.
tom subtypes of obsessive-
compulsive disorder and their 13 Thomsen PH, Mikkelssen HU,
relation to personality and tic dis- Development of personality disor-
orders, J Clin Psychiatry (1994) ders in children and adolescents
55(3, suppl.):18–23. in obsessive-compulsive disor-
der: a 6 to 22 year follow-up
5 Hollander E, Rosen J, Impulsivity, study, Acta Psychiatr Scand
J Psychopharmacol (2000) 14(2 (1993) 87(6):456–62.
suppl.):S39–44.
14 Miguel EC, Coffey BJ, Baer L,
6 Jarry JL, Vaccarino FJ, Eating dis- Savage CR, Rauch SL, Jenike
order and obsessive-compulsive MA, Phenomenology of intentional
disorder: neurochemical phenome- repetitive behaviors in obsessive-
nological commonalities, J Psych compulsive disorder and
Neurosci (1996) 21(1):36–48. Tourette’s disorder, J Clin Psychi-
7 McElroy SL, Phillips KA, Keck PE, atry (1995) 56:246–55.
15 American Psychiatric Association, 24 Rasmussen S, Eisen JL, Phenom-

Diagnostic and Statistical Manual enology of OCD: clinical sub-
of Mental Disorders, 4th edn types, heterogeneity and
(American Psychiatric Press: coexistence. In: Zohar J, Insel I,
Washington, 1994). Rasmussen S, eds, The Psy-
16 Como PG, Obsessive-compulsive chobiology of Obsessive-
disorder in Tourette’s syndrome, Compulsive Disorder (Springer:
Adv Neurol (1995) 65:281–91. New York, 1991) 13–43.
17 Leckman JF, Walker DE, Good- 25 Jenike MA, Baer L, Summergrad
man WK, Pauls DL, Cohen DJ, P, Weilburg JB, Holland A, Sey-
‘Just right’ perceptions associ- mour R, Obsessive-compulsive
ated with compulsive behavior in disorder: a double-blind,
Tourette’s syndrome, Am J Psy- placebo-controlled trial of
chiatry (1994) 151(5):675–80. clomipramine in 27 patients, Am J
Psychiatry (1989) 146:1328–30.
18 Leonard HL, Lenane MC, Swedo
SE, Rettew DC, Gershon ES, 26 Jenike MA, Hyman S, Baer L et al,
Rapoport JL, Tics and Tourette’s A controlled trial of fluvoxamine in
disorder: a 2- to 7-year follow-up obsessive-compulsive disorder:
of 54 obsessive-compulsive chil- implications for a serotonergic
dren, Am J Psychiatry (1992) theory, Am J Psychiatry (1990)
149(9):1244–51. 147:1209–15.
19 Pitman RK, Green RC, Jenike MA, 27 Goodman WK, Price LH, Ras-
Mesulam MM, Clinical compari- mussen SA, Delgado PL,
son of Tourette’s disorder and Heninger GR, Charney DS, Effi-
obsessive-compulsive disorder, cacy of fluvoxamine in obsessive-
Am J Psychiatry (1987) 144(9): compulsive disorder: a
1166–71. double-blind comparison with
placebo, Arch Gen Psychiatry
20 Miguel EC, Baer L, Coffey BJ et (1989) 26:123–8.
al, Phenomenological differences
appearing with repetitive behav- 28 Goodman WK, McDougle CJ,
iours in obsessive-compulsive Price LH, Riddle MA, Pauls DL,
disorder and Gilles de la Leckman JF, Beyond the sero-
Tourette’s syndrome, Br J Psychi- tonin hypothesis: a role for
atry (1997) 170:104–45. dopamine in some forms of
obsessive-compulsive disorder, J
21 Tourette Syndrome Classification Clin Psychiatry (1990) 51:36–43.
Study Group, Definitions and
classification of tic disorders, 29 Shapiro AK, Shapiro E, Treatment
Arch Neurol (1993) 50:1013–16. of Gilles de la Tourette’s syn-
drome with haloperidol, Br J Psy-
22 Shapiro AK, Shapiro E, Evaluation chiatry (1968) 114:345–50.
of the reported association of
obsessive-compulsive symptoms 30 Shapiro AK, Shapiro ES, The
or disorder with Tourette’s disor- treatment and etiology of tics and
der, Compr Psychiatry (1992) Tourette’s syndrome, Compr Psy-
33:152–65. chiatry (1981) 22:193–205.
23 George MS, Trimble MR, Ring 31 Shapiro AK, Shapiro E, Young JG,
HA, Sallee FR, Robertson MM, Gilles de la Tourette Syndrome,
Obsessions in obsessive- 2nd edn (Raven Press: New York,
compulsive disorder with and 1988).
without Gilles de la Tourette’s 32 McDougle CJ, Goodman WK,
syndrome, Am J Psychiatry Price JH et al, Neuroleptic addi-
(1993) 150(1):93–7. tion in fluvoxamine-refractory
obsessive-compulsive disorder, controlled crossover trial of the

Am J Psychiatry (1990) 147: efficacy of fluoxetine for trichotillo-
652–4. mania, Am J Psychiatry (1995)
33 McDougle CJ, Goodman WK, 152:1192–6.
Leckman JF, Lee NC, Heninger 42 Van Ameringen M, Mancini M,
GR, Price LH, Haloperidol addi- Oakman JM, Farvolden P, The
tion in fluvoxamine-refractory potential role of haloperidol in the
obsessive-compulsive disorder: a treatment of trichotillomania, J
double-blind, placebo-controlled Affect Disord (1999) 56:219–26.
study in patients with and without 43 Ninan PT, Knight B, Kirk L, Roth-
tics, Arch Gen Psychiatry (1994) baum BO, Kelsey G, Nemeroff
51:302–8. CB, Beyond panic: medication
34 Swedo SE, Leonard HL, Trichotil- effects in anxiety disorders: con-
lomania: an obsessive- trolled trial of venlafaxine in tri-
compulsive spectrum disorder? chotillomania: interim phase 1
Psychiatr Clin North Am (1992) results, Psychopharm Bull (1998)
15(4):777–90. 34:221–4.
35 Stein DJ, Hollander E, Low-dose 44 Stahl SM, Essential Psychophar-
pimozide augmentation of sero- macology: Neuroscientific Basis
tonin reuptake blockers in the and Practical Applications, 2nd
treatment of trichotillomania, J edn (Cambridge University Press:
Clin Psychiatry (1992) 53:123–6. New York, 2000).
36 Christenson GA, Mackenzie TB, 45 Mello LEAM, Villares J, Neu-
Mitchell JE, Characteristics of 60 roanatomy of the basal ganglia,
adult chronic hair pullers, Am J Psychiatr Clin North Am (1997)
Psychiatry (1991) 148:365–70. 10(4):691–704.
37 Yanchick JK, Barton TL, Kelly 46 Rauch SL, Savage CR, Neu-
MW, Efficacy of fluoxetine in tri- roimaging and neuropsychology
chotillomania, Ann Pharmacother of the striatum, Psychiatr Clin
(1994) 28:1245–6. North Am (1997) 10(4):741–68.
38 Swedo SE, Leonard HL, Rapoport 47 Miguel EC, Rauch SL, Jenike MA,
JL, Lenane MC, Goldberger EL, Obsessive-compulsive disorder,
Cheslow DL, A double-blind com- Psychiatr Clin North Am (1997)
parison of clomipramine and 10(4):863–83.
desipramine in the treatment of 48 O’Sullivan RL, Rauch SL, Breiter
trichotillomania, New Engl J Med HC et al, Reduced basal ganglia
(1989) 321:497–500. volumes in trichotillomania mea-
39 Christenson GA, Mackenzie TB, sured via morphometric reso-
Mitchell JE, Callies AL, A nance imaging, Biol Psychiatry
placebo-controlled, double-blind (1997) 42:39–45.
crossover study of fluoxetine in 49 Phillips KA, Kim JM, Hudson JI,
trichotillomania, Am J Psychiatry Body image disturbance in body
(1991) 148:566–71. dysmorphic disorder and eating
40 Stein DJ, Bouwer C, Hawkridge S, disorders. Obsessions or delu-
Emsley RA, Risperidone augmen- sions? Psychiatr Clin North Am
tation of serotonin reuptake (1995) 18(2):545–61.
inhibitors in obsessive-compulsive 50 Gamberino WC, Gold MS, Neuro-
and related disorders, J Clin Psy- biology of tobacco smoking and
chiatry (1997) 58(3):119–22. other addictive disorders, Psychi-
41 Streichenwein SM, Thornby JI, A atr Clin North Am (1999) 22(2):
long-term, double-blind, placebo- 301–29.
51 Hollander E, Buchalter AJ, AM, van der Gugten J, Kalsbeck

DeCaria CM, Pathological gam- A, Influence of the mesocortical
bling, Psychiatr Clin North Am dopaminergic system on activity,
(2000) 23(3):629–41. food hoarding, social agonistic
52 Koob GF, Neurobiology of addic- behavior, and spatial delayed
tions: toward the development of alternation in male rats, Behav
new therapies, Ann NY Acad Sci Neurosci (1989) 103(1):24–35.
(2000) 909:170–85. 55 Drago F, Lissandrello CO, The
53 Busatto GF, Kerwin RW, Schizo- ‘low dose’ concept and the para-
phrenia, psychosis, and the basal doxical effects of prolactin on
ganglia, Psychiatr Clin North Am grooming and sexual behaviour,
(1997) 10(4):897–910. Eur J Pharmacol (2000) 405(1–3):
131–7.
54 Stam CJ de Bruin JP, van Haelst
4
Unusual symptoms of OCD
Dan J Stein, Naomi Fineberg and Brian Harvey
Obsessive compulsive disorder (OCD) is in many ways one of the most

homogeneous of psychiatric disorders. Patients present with characteris-
tic symptoms of obsessions and compulsions, with concerns focusing on
contamination and other kinds of possible harm. While the exact content
of such symptoms may vary slightly from patient to patient (for example,
obsessions with dirt, germs or bodily secretions, or having to wash
hands, shampoo hair, or clean clothes), the form of symptoms (that is,
the focus on contamination) appears to be universal. Even when compar-
ing OCD in patients from vastly different cultures, the content of the
symptoms seems to differ only slightly, and the form is the same.1
Nevertheless, during the course of treating different patients with OCD,
clinicians are likely to come across symptoms that are relatively unusual.
These anomalous complaints raise several interesting issues: patients
with unusual OCD symptoms may present diagnostic dilemmas and be
misdiagnosed; exploration of the psychobiology of the symptoms may
provide new clues for understanding the pathogenesis of this disorder;
and such patients may require novel adjustments to their treatment
approach. In this chapter we review some unusual symptoms of OCD
with a focus on these clinically relevant matters.
‘Classical’ OCD
Before considering some of the less common OCD symptoms, it may be

useful to summarize the more typical presentations of the disorder.
Table 4.1 lists common OCD symptoms documented in a large group of
subjects.2 The most common symptoms are those that involve contami-
nation and possible harm. The possibility that procedural routines
revolving around such concerns are encoded in the basal ganglia is
consistent with a wealth of information suggesting that cortico–
striatal–thalamic–cortical (CSTC) circuits are crucial in mediating OCD. It
is also likely that such symptoms are mediated by the serotonin
37
Table 4.1 Classical symptoms of OCD.

Concerns about contamination → washing/cleaning rituals
Concerns about harm to self/others → checking rituals
Ordering/symmetry concerns → ordering/symmetry rituals
neurotransmitter system, which apparently has an important role in harm

assessment.
Factor analyses of OCD confirm the importance of these particular
symptoms. A recent study demonstrated four factors: cleanliness/wash-
ing; aggressive/sexual/religious obsessions/checking; ordering/symme-
try; and hoarding.3 Interestingly, ordering/symmetry symptoms have been
associated with comorbid tics, discussed in the next section. Other sec-
tions of this chapter focus on hoarding, and on unusual somatic, sensory,
stereotypic, impulsive, interpersonal and abstract symptoms. A final sec-
tion looks at aspects of OCD symptoms that may be associated with fail-
ure to respond to treatment.
OCD and tics
One of the important advances in recent understanding of OCD is a

recognition of the phenomenological and neurobiological overlap
between OCD and Tourette’s syndrome (TS). Up to 30% of patients with
OCD may manifest tics, while many patients with TS may meet criteria for
OCD. Even more convincingly, TS is more common than would be
expected in the families of OCD probands and vice versa.4 Recent work
on an autoimmune hypothesis of OCD demonstrates that both OCD
symptoms and tics may begin in the aftermath of a streptococcal
infection.5
Interestingly, a number of symptoms are more likely to be seen in OCD
patients with tics than in those without tics. In a comparison of patients
with OCD and patients with both OCD and TS, the former group were
more likely to have contamination obsessions and compulsions, fear of
not saying the right thing, and body dysmorphic disorder; while the latter
group were more likely to have an obsession with the need for symmetry
accompanied by magical thinking, fear of doing something embarrassing
or blurting out an obscenity, intrusive violent and/or sexual images and
thoughts, touching compulsions, blinking or staring rituals, self-injurious
compulsions, hoarding and counting.6 Similarly, Holtzer and colleagues
found that OCD patients with a history of tic disorder had significantly
more touching, repeating, blinking, self-damaging, counting, and order-
ing compulsions.7 Coprolalia, which is not uncommon in TS, is only rarely
seen in OCD patients without tics.8
Unusual symptoms 39
The existence of these relatively unusual OCD symptoms or of comor-

bid tics may reflect specific psychobiological processes that overlap with
those found in TS. It has been suggested, for example, that the putamen
plays a particularly important role in TS, whereas classical OCD involves
the caudate (see Chapter 3).9 Certainly, the dopamine system is likely to
play a central role in TS, with dopamine-receptor antagonists constituting
the treatment of choice in this disorder. Furthermore, OCD patients with
tics are less likely to respond to serotonin reuptake inhibitors (SRIs) and
more likely to respond to augmentation of these agents with a typical
antipsychotic agent.10
Hoarding symptoms
Although perhaps not that uncommon in OCD, hoarding is sufficiently dif-

ferent to warrant mention in a separate discussion. Hoarding has been
defined as the acquisition of, and failure to discard, possessions that are
useless or have limited value.11 In contradistinction to normal collecting,
hoarding may be a symptom of various psychiatric disorders including
OCD and obsessive-compulsive personality disorder (OCPD). The spe-
cific rationale for hoarding in OCD may vary from patient to patient, but
compulsive hoarders may be characterized by a relative lack of insight.12
Hoarding in OCD may be associated with significant morbidity, may
have specific neurobiological and psychological correlates, and may
respond to pharmacotherapy or psychotherapy.13 Of particular note is the
possibility that, like comorbid tics, hoarding is a predictor of failure to
respond to SRIs.14,15 The basic neurobiology of hoarding involves
dopamine, and it may be speculated that dopamine blocker augmenta-
tion is again a useful option in OCD patients where hoarding is a predom-
inant symptom.
Unusual somatic symptoms
It has been suggested that at least a third of OCD patients have somatic
concerns.16 Contamination itself could conceivably be included under the
rubric of a somatic concern, but for the purposes of the current discus-
sion the latter term can be taken to refer primarily to obsessions or com-
pulsions related to the appearance or health of one’s body.
Excessive concern about the appearance of one’s body is the hallmark
of body dysmorphic disorder (BDD). There is a good deal of overlap in
the phenomenology of OCD and BDD, insofar as BDD patients also have
recurrent intrusive thoughts (about body appearance) and ritualistic
behaviours (e.g. mirror-checking, asking for reassurance about their
appearance, skin-picking). Concerns often centre on the face, breasts or
buttocks, but any area of the body can be a focus of attention.17 As in the
case of OCD, insight into the excessive or irrational nature of symptoms
varies from person to person. The degree to which some sufferers self-
mutilate in response to their obsessions has received increased recogni-
tion recently.
Excessive concerns about the health of one’s body is the defining
characteristic of hypochondriasis. Once again, the phenomenology of
this disorder may show considerable overlap with OCD – there are intru-
sive concerns which increase anxiety, followed by repetitive behaviours
(e.g. reading about illness, visiting the doctor) which attempt to decrease
anxiety levels.18 Patients with OCD, in addition to their other symptoms,
may worry about specific illnesses (in the past, concerns centred often
on tuberculosis or cancer, now a typical concern is AIDS).
The Diagnostic and Statistical Manual DSM-IV rules out the diagnosis
of BDD and hypochondriasis when symptoms are better explained by
OCD.19 In clinical practice, though, there are patients whose symptoms
seem to fall at the intersection of these three disorders.20 An excessive
concern that one’s teeth have been contaminated by an antibiotic and
are pathologically yellow, for example, is one that has elements of OCD
(contamination), BDD (appearance) and hypochondriasis (illness). In a
patient with such a concern, and without any other obsessions or com-
pulsions, the exact diagnosis would naturally reflect clinical judgment.
The putative diagnosis of ‘multiple chemical sensitivity’ would also seem
to lie at this intersection in some cases.
Bowel and urinary obsessions may be categorized together with
somatic obsessions. Although there is again the possibility of an overlap
with contamination concerns, the main focus of obsessions and compul-
sions in these patients is on their bowel or urinary habits or processes.
Although there is little specific research on these patients,21 standard
anti-OCD interventions can be suggested.
Olfactory reference syndrome (ORS) also falls under the rubric of
somatic obsessions. This term was introduced by Pryse-Phillips to differ-
entiate non-specific concerns about personal odour, seen in a range of
psychiatric disorders, from a specific condition in which such concerns
were the chief characteristic.22 Thus, patients with ORS held themselves
responsible for the odour, and therefore experienced a ‘contrite reaction’,
characterized by shame and embarrassment. Such patients ‘tended to
wash themselves excessively, to change their clothes with more than
usual frequency, to hide themselves away, and to restrict their social and
domestic excursions’. Again, there are obvious phenomenological simi-
larities with OCD, and such patients have been reported to respond to
SRIs.23
Interestingly, a number of ‘culture-bound’ syndromes also appear to
revolve around somatic concerns. Koro, a condition seen in Asian coun-
tries, is characterized by concerns that the penis is shrinking. The disor-
Unusual symptoms 41
der arguably meets diagnostic criteria for body dysmorphic disorder.24

However, there are also some apparent differences between koro and
BDD; for example, koro concerns may have a sudden onset, may be
accompanied by panic, and may on occasion occur in epidemics. Taijin
kyofusho (TKS) or anthropophobia is a condition seen in Japan, in which
there is a fear of social situations. In many ways the disorder appears
similar to social anxiety disorder, except that subjects are concerned less
with embarrassing themselves, and more with offending others.25 Typical
symptoms in TKS include concerns about one’s body odour being offen-
sive to others. Interestingly, this disorder may respond to treatment with
SRIs.26 Thus, although TKS is unlikely to overlap entirely with either social
anxiety disorder or OCD, some TKS patients may well have symptoms
that are redolent of the form of these disorders.
Finally, consider ‘reverse anorexia nervosa’ or ‘muscle dysmorphia’.
Pope and colleagues used these terms to describe a hypothetical sub-
type of BDD characterized by pathological preoccupation with muscu-
larity.27,28 They suggest that this disorder may cause severe subjective
distress, impaired social and occupational functioning, and abuse of
anabolic steroids and other substances. Preliminary data suggest that
the syndrome is far from uncommon.
Unusual sensory symptoms
Obsessions in OCD typically involve particular ideas or thoughts. How-

ever, at times obsessions primarily involve visual images, music or
sounds, or the recall of past memories. In patients with Tourette’s syn-
drome, tics may be preceded by premonitory urges, but sensory symp-
toms such as these are more common in TS than in OCD patients.29
Whereas musical hallucinations by definition have ‘the compelling
sense of reality of a true perception’,29 the source of which is often experi-
enced as outside the head, in musical obsessions tunes are experienced
as an internally generated cognitive product that is intrusive and inappro-
priate. Repetitive musical intrusions have been described after basal
ganglia pathology,30 and single photon emission computed tomography
(SPECT) scanning of two patients with musical obsessions demonstrated
prominent decreases of blood flow in the temporal lobes as well as
frontal perfusion defects.31 This is consistent with a literature demonstrat-
ing the involvement of the temporal lobe in normal processing of music,32
musical hallucinations,33 and musicogenic epilepsy.34 Interestingly, there
are case reports of obsessive musical symptoms responding to an SRI.35
The occasional predominance of past memories as an OCD obsession
may raise the question of differential diagnosis with post-traumatic stress
disorder (PTSD). In PTSD there may be intrusive memories of a traumatic
event, and there may also be a certain amount of compulsive behaviour
(washing after rape is not uncommon). Certainly, PTSD can potentially be

misdiagnosed as OCD, and vice versa.36 Although neurobiological
research on PTSD has emphasized the role of the amygdala–hippocam-
pus rather than cortico–striatal–thalamic–cortical (CSTC) circuits, there
may nevertheless be some overlap in the psychobiology of these two dis-
orders. Thus, the serotonin agonist methylchlorophenylpiperazine
(mCPP) can exacerbate symptoms in both conditions, and it is possible
that the SRIs are selectively effective in both.
Another disorder in which sensory-like symptoms occur, and which
arguably also has a somatic element, is depersonalization. Here there
are repetitive concerns about the reality of one’s sense of self. Although
classified as a dissociation disorder, such symptoms may be experi-
enced as intrusive. There is evidence that depersonalization is mediated
by the serotonin system and may respond to serotonin reuptake
inhibitors.37
Unusual stereotypic symptoms
Stereotypic movement disorder is described in DSM-IV as characterized

by repetitive, seemingly driven, but non-functional motoric behaviour that
is not better accounted for by compulsions and tics.19 Stereotypic move-
ment disorder (SMD) should also be differentiated from the motor stereo-
typies (or ‘punding’) seen secondary to central nervous system
stimulants such as amphetamine and cocaine,38 and from perseverative
symptoms secondary to various kinds of brain lesion.39
The stereotypies of SMD are redolent of animal stereotypies, insofar as
they involve rhythmic, repeated, purposeless behaviour.40 There is a rich
animal literature demonstrating that stereotypies can be elicited reliably
by physical confinement or emotional deprivation, as well as by manipu-
lations of the dopamine and other systems. More recently, there has
been increased attention to behaviour such as paw-licking in dogs (acral
lick dermatitis), hair-pulling in cats (psychogenic alopecia), and feather-
picking in birds, as possible analogues of OCD.41
In humans the line between stereotypies and compulsions is not
always clearly discernible. There is the occasional OCD patient, for
example, who has to sniff (sometimes in response to contamination con-
cerns, but sometimes simply ritualistically), or who has a compulsion to
blink, to swallow, or to make some other movement.42 Also, self-injurious
stereotypies such as skin-picking are not uncommon in OCD, body dys-
morphic disorder, and trichotillomania.43 Stereotypies may also overlap
with tics, and perhaps even with stuttering, although they differ to the
extent that they are under more complete voluntary control.
Conversely, some patients with symptoms such as head-banging or
body-rocking, which might well fall under the diagnosis of stereotypic
Unusual symptoms 43
movement disorder, may describe their symptoms in a way that is very

reminiscent of OCD. While some patients with self-injurious stereotypies
(such as skin-picking, nail-biting, nose-picking) may describe their symp-
toms in terms of tension relief (so paralleling the symptoms of an impulse
control disorder), others describe their symptoms as ritualistic and
senseless (so approaching a compulsion).43,44
Unusual impulsive symptoms
Some authors have suggested that one way of looking at the OCD spec-
trum may be in terms of the dimension of compulsivity and impulsiv-
ity.45–47 This perspective is based on the notion that compulsivity may
reflect harm avoidance, whereas impulsivity reflects risk-seeking. Thus
OCD falls at the compulsive end of an OCD spectrum, whereas impulsive
disorders (e.g. pathological gambling, kleptomania, pyromania, uncon-
trolled buying) fall at the impulsive end, and disorders such as Tourette’s
syndrome, trichotillomania and obsessive-compulsive personality disor-
der demonstrate both compulsive and impulsive characteristics.
Nevertheless, there are patients with supposedly impulsive disorders in
whom there is also apparent overlap of compulsive and impulsive symp-
toms. Occasionally a patient with kleptomania, for example, will describe
having to steal exactly three items on each occasion. Perhaps more com-
monly, patients with kleptomania will hoard stolen goods in a way that is
particularly reminiscent of OCD. (Conversely, of course, some patients
with OCD or TS may have considerable comorbid impulsive-aggression.)
Indeed, the overlap between compulsive and impulsive aspects of
symptoms is one that is often useful to consider. As noted above, self-
injurious behaviours such as skin-picking may have both compulsive and
impulsive features. Similar claims can arguably be made about symp-
toms such as trichotillomania and trichophagy,48 and about the range of
symptoms (including concerns about food contamination or difficulty in
swallowing) in various eating disorders (anorexia nervosa, bulimia ner-
vosa, pica, polydipsia).49
Unusual interpersonal symptoms
Jealousy may be a normal or pathological phenomenon.50 Pathological

jealousy has been divided into reactive jealousy, which appears to result
from an interaction between pre-existing personality and the experience
of a threat to the relationship; and symptomatic jealousy, which results
from an underlying disease process.51 Classifications of pathological jeal-
ousy have often focused on delusions. Kraft-Ebbing, for example, divided
these into delusions of infidelity (where the patient’s conjugal partner was
under suspicion) and delusions of jealousy (when the patient’s partner in

an extramarital affair was under suspicion).52 Stalking and erotomania fall
within the spectrum of these conditions.
Classifications of pathological jealousy have only rarely included a cat-
egory of obsessional jealousy.53 Nevertheless, this category would
appear useful insofar as jealous thoughts may be experienced as intru-
sive and excessive, and may lead to compulsive behaviours such as
checking. Ego-dystonicity in both classical OCD symptoms and patho-
logical jealousy varies considerably from patient to patient, and the
notion of a spectrum from obsessional to delusional may therefore be
useful here. Interestingly, however, both cognitive-behavioural therapy
and SRIs have been reported as useful in obsessional jealousy.54
There is also the question of what has been termed ‘compulsive’ sexual
behaviour. Strictly speaking this does not always fall into the ‘interper-
sonal’ category: compulsive masturbation, for example, can take place
when the person is alone (although typically even this is accompanied by
fantasies of the interpersonal). Furthermore, clinicians should be careful
to differentiate classical obsessions with sexual content (e.g. ego-
dystonic homosexual images in a heterosexual person), paraphilias, and
compulsive sexual behaviour (also termed non-paraphilic sexual addic-
tion and hypersexual disorder).55
Obsessive compulsive disorder often insinuates itself within an inter-
personal relationship. For example, a patient may repeatedly ask a family
member for reassurance, and feel relief of anxiety only upon hearing a
particular phrase. When family members become active participants in
the rituals, there is even the risk of a folie à deux.56 Furthermore, cases of
trichotillomania or body dysmorphic disorder by proxy – with symptoms
focused on another – have been described. These points emphasize the
clinical importance of a thorough family history, and of including signifi-
cant others in the treatment plan.
Unusually abstract symptoms
In children, symptoms of OCD can be quite concrete. A child may wash

repeatedly without necessarily being able to articulate a clear rationale
for this behaviour. On the other hand, some adults develop symptoms of
OCD that are remarkably abstract. These patients, who would perhaps at
one time have been termed ‘pure obsessionals’, may have complex men-
tal rituals with complex series of arguments running through their heads
and justifying their current actions.
One patient of ours is particularly interesting to mention in this regard.
This was a patient who during a philosophy course began to be
obsessed with the idea that everything he knew or perceived might in
fact be imaginary. Initially this began simply as a philosophical debate,
Unusual symptoms 45
but its persistence was felt as intrusive and senseless. In order to get rid
of the thought, he felt compelled to go through a mental argument that
would prove the reality of his knowledge and perceptions. This argument
would take some time to complete, and until a satisfactory conclusion
was reached, he felt intensely anxious. Fortunately, he responded to
treatment with an SRI.
Another abstract kind of symptom is that of scrupulosity. Some of the
earliest published cases of individuals with symptoms redolent of OCD
described those who were concerned about their spiritual flaws, and who
subsequently made ritualistic expiation. Fortunately, a growing literature
arguing that such symptoms respond to standard OCD treatments is now
available. Both cognitive-behavioural interventions and medication may
be useful.57
The term ‘impulsions’ was employed by Bender and Schilder to
describe a childhood phenomenon in which there was preoccupation
with a specific subject (e.g. motor cars), leading to the performance of
specific actions (e.g. painting cars).58 These differed from obsessions
and compulsions in that patients were not bothered by them. Although no
longer much used, this construct remains relevant both to disorders such
as Asperger’s syndrome, and arguably also to concepts of subclinical
OCD or obsessive compulsive personality disorder.
Unusually problematic symptoms
Some OCD patients seem to be particularly difficult to treat. This may

have to do with the particular form of the presenting symptoms, with
increased severity of symptoms, or with Axis I or II comorbidity. Consider,
for example, patients whose obsessions and compulsions revolve around
physicians – ‘has the psychiatrist made an accurate diagnosis?’ – or
around medications – ‘is this tablet contaminated?’ Patients who have
poor insight may refuse to come in for treatment, may not immediately be
diagnosed as having OCD, and may be at risk for non-compliance. Such
patients can be extremely challenging.
Lack of insight should be differentiated from the degree to which a
symptom is bizarre. Of course, the whole question of what is or is not
bizarre is a matter of some debate;59 but clearly some OCD symptoms
are entirely understandable (concerns about acquiring AIDS after unpro-
tected sex), while others are less so (concerns that one has made a
woman pregnant simply by looking at her); whether or not such symp-
toms have a different neurobiology has not to our knowledge been
studied.
One OCD symptom type that may be significantly problematic is
‘obsessional slowness’. Patients with obsessional slowness demonstrate
pathological orderliness – having to undertake tasks in a precise and
particular pattern. In the original description, ‘primary obsessional slow-

ness’ was differentiated from slowness secondary to rituals.60 However,
later authors have argued that such cases can invariably be reanalysed
as secondary to obsessions, compulsions or avoidance strategies.61
Hymas and colleagues found that patients with obsessional slowness
invariably have increased neurological soft signs.62 Slowness of thinking
(bradyphrenia) and slowness of movement (bradykinesia) are symptoms
of subcortical dementia, seen in disorders of the basal ganglia such as
Parkinson’s disease. Similarly, it might be suggested that obsessional
slowness in OCD patients reflects basal ganglia damage. Perhaps this is
not so much a separate group of OCD patients, as a subtype with more
severe psychopathology. It has been suggested that these patients are
less responsive to cognitive-behavioural therapy.63
In the context of disorders such as schizophrenia, OCD is problematic
insofar as there may be accompanying loss of insight by the patient, or
underdiagnosis by the clinician. Obsessive compulsive disorder is not
uncommon in borderline personality disorder, and the combination of dis-
orders may be associated with a poorer response to treatment. The
extent to which OCD can be precipitated by childhood trauma has not
received a great deal of attention, and perhaps deserves more. The dis-
order may also be seen during pregnancy, or secondary to various med-
ical conditions; such circumstances demand an adaptation of usual
treatments.
Conclusion
Although many patients with OCD present with ‘classical’ symptoms, a
range of other, more unusual symptoms may also be seen. Some of
these symptoms may unfortunately lead to delayed diagnosis, and others
may interfere with treatment. It is important for clinicians to be aware of
the range of unusual presentations of OCD to maximize appropriate diag-
nosis and early intervention.
An examination of more unusual symptoms may raise questions about
current nosology. Although it is important not to oversimplify the construct
of an OCD spectrum, the apparently close relationship between OCD,
BDD and hypochondriasis certainly raises questions for future investiga-
tion about possible overlaps in the psychobiology of these disorders. A
putative OCD spectrum of disorders may include conditions that have
been considered ‘culture-bound’.
It is remarkable that classical OCD, more unusual OCD symptoms, and
some of the putative OCD spectrum disorders appear to respond selec-
tively to the SRIs.64 Further study of patients with more unusual symptoms
may ultimately shed additional light on the psychobiology of OCD. The
failure of patients with hoarding or with comorbid tics, for example, to
Unusual symptoms 47
respond to SRIs, points to the involvement of other neurotransmitter sys-

tems and suggests alternative routes of clinical intervention and future
investigation.
Acknowledgement
Professors Stein and Harvey are supported by the Medical Research
Council of South Africa.
References
1 Stein DJ, Rapoport JL, Cross- 7 Holtzer JC, Price LH, McDougle
cultural studies and obsessive- CJ et al, Obsessive compulsive
compulsive disorder, CNS Spectr disorder with and without a
(1996) 1:42–6. chronic tic disorder: a compari-
2 Rassmussen SA, Eisen JL, Epi- son of symptoms in 70 patients,
demiological and clinical features Br J Psychiatry (1994) 164:
of obsessive-compulsive disor- 469–73.
der. In: Jenike MA, Baer LB, 8 Pitman RK, Jenike MA, Coprolalia
Minichiello WE, eds, Obsessive- in obsessive-compulsive disor-
Compulsive Disorders: Theory der: a missing link, J Nerv Ment
and Management, 2nd edn (Year Dis (1988) 176:311–13.
Book: Chicago, 1990). 9 Rauch SL, Baxter LR, Neuroimag-
3 Leckman JF, Grice DE, Board- ing in obsessive-compulsive dis-
man J et al, Symptoms of order and related disorders. In:
obsessive-compulsive disorder, Jenicke MA, Baer L, Minichiello
Am J Psychiatry (1997) 154: WE, eds, Obsessive-Compulsive
911–17. Disorders: Practical Management,
4 Pauls DL, Towbin KE, Leckman 3rd edn (Mosby: St Louis, 1998).
JF et al, Gilles de la Tourette’s 10 McDougle CJ, Goodman WK,
syndrome and obsessive compul- Leckman JF et al, Haloperidol
sive disorder: evidence support- addition in fluvoxamine-refractory
ing a genetic relationship, Arch obsessive-compulsive disorder: a
Gen Psychiatry (1986) 43: double-blind placebo-controlled
1180–2. study in patients with and without
5 Swedo SE, Leonard HL, Garvey tics, Arch Gen Psychiatry (1994)
M et al, Pediatric autoimmune 51:302–8.
neuropsychiatric disorders asso- 11 Frost RO, Gross RC, The hoard-
ciated with streptococcal infec- ing of possessions, Behav Res
tions: clinical description of the Ther (1993) 31:367–81.
first 50 cases, Am J Psychiatry
(1998) 155:264–71. 12 Greenberg D, Compulsive hoard-
ing, Am J Psychother (1987) 41:
6 George MS, Trimble MR, Ring HA 409–16.
et al, Obsessions in obsessive-
compulsive disorder with and 13 Stein DJ, Seedat S, Potocnik F,
without Gilles de la Tourette’s Hoarding: a review, Isr J Psychia-
syndrome, Am J Psychiatry try (1999) 36:35–46.
(1992) 150:93–7. 14 Black DW, Monahan P, Gable J et
al, Hoarding and treatment compulsive spectrum? Two cases

response in 38 nondepressed and a discussion, J Neuropsych
subjects with obsessive- Clin Neurosci (1998) 10:96–9.
compulsive disorder, J Clin Psy- 24 Stein DJ, Frenkel M, Hollander E,
chiatry (1998) 59:420–5. Classification of Koro, Am J Psy-
15 Mataix-Cols D, Rauch SL, Manzo chiatry (1991) 148:1279–80.
PA, Jenike MA, Baer L, Use of 25 Kleinknecht RA, Dinnel DL,
factor-analyzed symptom dimen- Tanouye-Wilson S, Lonner WJ,
sions to predict outcome with Cultural variation in social anxiety
serotonin reuptake inhibitors and and phobia: a study of Taijin
placebo in the treatment of Kyofusho, Behav Ther (1994)
obsessive-compulsive disorder, 17:175–8.
Am J Psychiatry (1999) 156:
26 Matsunaga H, Kiriike N, Matsui T,
1409–16.
Iwasaki Y, Nagata T, Stein DJ,
16 Simeon D, Hollander E, Stein DJ, Taijin Kyofusho: a form of social
Cohen LJ, Aronowitz B, Body anxiety disorder that responds to
dysmorphic disorder in the serotonin reuptake inhibitors? Int
DSM-IV field trial for obsessive- J Neuropsychopharmacol, in
compulsive disorder, Am J Psy- press.
chiatry (1995) 152:1207–9.
27 Pope HG, Katz DL, Hudson JI,
17 Phillips KA, McElroy SL, Keck PE, Anorexia nervosa and ‘reverse
Pope HG, Hudson JI, Body dys- anorexia’ among 108 male body-
morphic disorder: 30 cases of builders, Compr Psychiatry
imagined ugliness, Am J Psychia- (1993) 34:406–9.
try (1993) 150:302–8.
28 Pope HG, Gruber AJ, Choi P et al,
18 Fallon BA, Schneier FR, Marshall Muscle dysmorphia, Psychoso-
R et al, The pharmacotherapy of matics (1997) 38:548–57.
hypochondriasis, Psychopharma- 29 Miguel EC, do Rosario Campos
col Bull (1996) 32:607–11. MC, Prado HS et al, Sensory phe-
19 American Psychiatric Association, nomena in obsessive-compulsive
Diagnostic and Statistical Manual disorder and Tourette’s disorder,
of Mental Disorders, 4th edn J Clin Psychiatry (2000) 61:
(APA: Washington, 1994). 150–6.
20 Josephson SC, Hollander E, Fal- 30 Wodarz N, Becker T, Deckert J,
lon B, Stein DJ, Obsessive- Musical hallucinations associated
compulsive disorder, body with post thyroidectomy
dysmorphic disorder, and hypoparathyroidism and symmet-
hypochondriasis: three variations ric basal ganglia calcifications, J
on a theme, CNS Spectr (1996) Neurol Neurosurg Psych (1995)
1:24–31. 58:763–4.
21 Jenike MA, Vitagliano HL, Rabi- 31 Zungu-Dirwayi M, Hugo F, van
nowitz J et al, Bowel obsessions Heerden B, Stein DJ, Are musical
responsive to tricyclic antidepres- obsessions a temporal lobe phe-
sants in four patients, Am J Psy- nomenon? J Neuropsych Clin
chiatry (1987) 144:1347–8. Neurosci (1999) 11:398–400.
22 Pryse-Phillips W, An olfactory ref- 32 Lechevalier B, Platel H, Eustache
erence syndrome, Acta Psychiat F, Neuropsychology of musical
Scand (1971) 47:484–509. identification, Rev Neurol (Paris)
23 Stein DJ, Le Roux L, Bouwer C, (1995) 151:505–10.
van Heerden B, Is olfactory refer- 33 Berrios GE, Musical hallucina-
ence syndrome on the obsessive- tions: a historical and clinical
Unusual symptoms 49
study, Br J Psychiatry (1990) Psychiatr Ann (1998) 28:307–12.

156:188–94. 44 Jefferson JW, Thompson TD,
34 Wieser HG, Hungerbuhler H, Rhinotillexomania: psychiatric dis-
Siegel AM, Buck A, Musicogenic order or habit? J Clin Psychiatry
epilepsy: review of the literature (1995) 56:56–9.
and case report with ictal single 45 Stein DJ, Hollander E, The spec-
photon emission tomography, trum of obsessive-compulsive
Epilepsia (1997) 38:200–7. related disorders. In Hollander E
35 Cameron OG, Wasielewski P, (ed.) Obsessive-Compulsive
Clomipramine treatment of possi- Related Disorders (American Psy-
ble atypical obsessive- chiatric Press: Washington, 1993).
compulsive disorder, J Clin 46 Stein DJ, Hollander E, Impulsive
Psychopharmacol (1990) 10: aggression and obsessive-
375–6. compulsive disorder, Psychiatr
36 Pitman RK, Posttraumatic Ann (1993) 23:389–95.
obsessive-compulsive disorder: a 47 McElroy SL, Phillips KA, Keck PE,
case study, Compr Psychiatry Obsessive-compulsive spectrum
(1993) 34:102–7. disorders, J Clin Psychiatry
37 Hollander E, Liebowitz MR, (1994) 55:33–51.
DeCaria M et al, Treatment of
48 Bouwer C, Stein DJ, Trichobe-
depersonalization with serotonin
zoars in trichotillomania: case
reuptake blockers, J Clin Psy-
report and literature review, Psy-
chopharmacol (1990) 10:200–3.
chosom Med (1998) 60:658–60.
38 Schiorring E, Psychopathology
49 Stein DJ, Bouwer C, Van Heerden
induced by ‘speed drugs’, Phar-
B, Pica and the obsessive-
macol Biochem Behav (1981)
compulsive spectrum disorders,
14S1:109–22.
S Afr J Psychiatry (1996) 86:
39 Ames D, Cummings JL, Wirshing 1586–92.
WC et al, Repetitive and compul-
50 Shepard M, Morbid jealousy:
sive behavior in frontal lobe
some clinical and social aspects
degenerations, J Neuropsych Clin
of a psychiatric symptom, J Ment
Neurosci (1994) 6:100–13.
Sci (1961) 107:687–753.
40 Ridley RM, The psychology of
perseverative and stereotyped 51 White GK, Mullen PE, Jealousy:
behavior, Prog Neurobiol (1994) Theory, Research and Clinical
44:221–31. Strategies (Guildford: New York,
1989).
41 Dodman N, Moon A, Stein DJ,
Animal models of obsessive- 52 Kraft-Ebbing R von, Ueber Eifer-
compulsive disorder. In: Hollan- suchtswahn beim Manne, J Psy-
der E, Stein DJ, eds, Obsessive- chiat Neurol (1892) 10:212–31.
Compulsive Disorders: Etiology, 53 Mooney HB, Pathological jealousy
Diagnosis, Treatment (Marcel and psychochemotherapy, Br J
Dekker: New York, 1997). Psychiatry (1965) 111:1023–42.
42 Zella SJ, Geenens DL, Horst 54 Stein DJ, Hollander E, Serotonin
JN. Repetitive eructation as a reuptake blockers for the treat-
manifestation of obsessive- ment of obsessional jealousy, J
compulsive disorder, Psychoso- Clin Psychiatry (1994) 55:30–3.
matics (1998) 39:299–301. 55 Stein DJ, Black DW, Pienaar W,
43 Stein DJ, Niehaus DJH, Seedat S, Sexual disorders not otherwise
Emsley RA, Phenomenology of specified: Compulsive, impulsive
stereotypic movement disorder, or addictive? CNS Spectr (2000)
5(1):60–4. 61 Veale D, Classification and treat-

56 Torch EM, Shared obsessive- ment of obsessional slowness, Br
compulsive disorder in a married J Psychiatry (1993) 162:198–203.
couple: a new variant of folie a 62 Hymas N, Lees A, Bolton D et al,
deux? J Clin Psychiatry (1996) The neurology of obsessional
57:489. slowness, Brain (1991) 114:
57 Fallon BA, Liebowitz MR, Hollan- 2203–33.
der E et al, The pharmacotherapy 63 Clark DA, Sugrim I, Bolton D, Pri-
of moral or religious scrupulosity, mary obsessional slowness: a
J Clin Psychiatry (1990) 51: nursing treatment programme
517–21. and a 13 year old male adoles-
58 Bender L, Schilder P, Impulsions: cent, Behav Res Ther (1982) 20:
a specific disorder of the behav- 289–92.
ior of children, Arch Neurol 64 Stein DJ, Advances in the neuro-
Psychiat (1940) 44:990–1008. biology of obsessive-compulsive
59 Spitzer RL, First MB, Kendler KS, disorder: Implications for concep-
Stein DJ, The reliability of three tualizing putative obsessive-
definitions of bizarre delusions, compulsive and spectrum
Am J Psychiatry (1993) 150: disorders, Psychiatr Clin North
880–4. Am (2000) 23:545–62.
60 Rachman SJ, Primary obsessional
slowness, Behav Res Ther (1974)
12:9–18.
5
Obsessive compulsive disorder and
quality of life
Lorrin M Koran
The quality of a person’s life cannot be captured simply. Life is too

multifaceted, and each facet’s value is not universally agreed. More-
over, no simple metric exists for adding or subtracting one facet’s value
to that of another. Nonetheless, policy-makers, health-care payers and
physicians have become interested in measuring the impact of medical
interventions not only on the symptoms of a disease or disorder, but
also on the quality of the patient’s life. The crassest motives are eco-
nomic: to carve out a niche in the medical marketplace by arguing that
larger effects on some aspect of quality of life justify the selection of a
particular treatment. More defensible motives are humanitarian: to find
those treatments that bring the broadest and largest benefits to the
patient.
Physicians attempt to quantify medicine’s contribution to patients’
health-related quality of life (HRQL) in their role as advocates for the
whole person, and in response to the increasing political scrutiny of the
high costs of medical services and technologies. The 1990s saw the
publication of hundreds of studies concerning numerous diseases and
the creation of a specialized journal, Quality of Life Research, to commu-
nicate research findings. However, the study of health-related quality of
life is still a young discipline, and the portion devoted to obsessive com-
pulsive disorder (OCD) is in its infancy.
Attempts to measure ‘quality of life’ have brought the realization that
the concept is not only multifaceted, but also culturally bound. To allow
collaborative research across national boundaries, expert panels have
helped the World Health Organization create a quality of life assessment
questionnaire that is valid cross-culturally.1 The six broad domains of this
thoughtfully designed questionnaire have conceptual appeal: these
domains are physical; psychological; level of independence; social rela-
tionships; environment; and spirituality/religion/personal beliefs. Of
course, many other conceptual schemes have been used.2,3 Thus, this
chapter’s summary of information concerning HRQL in adults with OCD is
constrained by having to draw on studies using disparate methodologies.
51
Relationships between OCD and quality of life
The five studies that have examined aspects of HRQL in individuals with
OCD are all limited by ascertainment bias, and most suffer from small
sample size and questions about the construct validity of the assessment
instruments. These methodological limitations require us to view the
results with caution. Moreover, results describing individuals attending for
treatment of OCD should not be generalized to individuals with OCD in the
community who have not sought care, since their condition may be milder
or more likely to be transient or episodic.4,5 The reverse is also true.
An early study of HRQL in OCD involved a survey of 200 members of
the Obsessive-Compulsive Disorder Association of South Africa by
means of a detailed self-report questionnaire.6 Seventy-five question-
naires were returned (37.5% of those mailed), of which 39 reported OCD
symptoms and the remainder only noted hair-pulling. The individuals with
OCD had a mean age of 33.4 years (SD 14.5, range 11–68 years) and
about half were female. All but one were white, and of the adults, 15
(44%) were married, 2 (6%) were widowed and 17 (50%) were single.
The respondent’s HRQL was impaired in many domains. More than
half reported that OCD caused moderate or severe interference with
socializing, family relationships and ability to study; 30% reported moder-
ate or severe interference with ability to work. A little less than half
reported that their current obsessions or compulsions caused moderate
or severe distress. Three-quarters had decreased self-esteem and half
had thought about suicide.
A similar questionnaire survey, albeit of a much larger sample, was
conducted among members of the Obsessive Compulsive Foundation, a
US patient advocacy, education and lobbying organization.7 The investi-
gators surveyed every fourth member and received responses from
about one-quarter (26.9%) of those surveyed (701 of 2670). The respon-
dents had a mean age of 37 years (SD 14, range 5–82 years). Parents,
guardians or close relatives completed young children’s questionnaires.
A little more than half the respondents (55%) were women, and the
majority (95%) were white.
The pattern of impairment of HRQL domains closely resembled the
pattern described in South Africa. The OCD had interfered with the social
and work functioning of more than half the respondents, and for nearly
two-thirds it had interfered with their socializing or making friends; OCD
caused difficulties in family relationships for almost three-quarters of the
respondents. Among those previously employed, OCD had prevented
about 40% of respondents working, in many cases for more than a year.
About 20% of the respondents received disability income payments
when unemployed, substantiating the direct social costs as well as the
personal costs of the disorder. Impaired vocational functioning was
Quality of life 53
suggested by the observation that the respondents’ average career

achievement did not match their educational attainment, i.e. the respon-
dents’ mean income resembled that of the general population despite
their much higher level of education (college degrees, 40% versus
14.7%, and postgraduate degrees, 18% versus 7.5%).8
The HRQL domain of general wellbeing was usually diminished: obses-
sions caused moderate to severe distress for 59% of respondents and
compulsions brought these distress levels to 51%. Moreover, lowered
self-esteem was present in more than 90%, thoughts of suicide had both-
ered more than half, and one-eighth had been led to a suicide attempt.
Reduced wellbeing was also reflected in the abuse of alcohol (reported
by 18%) and of other drugs (13%).
Only one study has compared OCD patients’ HRQL to norms for the
general population and for individuals with another chronic disorder.
Koran and his colleagues studied 60 medication-free outpatients with
moderate to severe OCD who were enrolling in a medication trial.9 The
comparison norms were established in an independent study,10 which
limits but does not invalidate the comparisons. The HRQL was assayed
with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-
36), a self-report questionnaire.11 The SF-36 generates measures of phys-
ical domains of HRQL (physical functioning; role limitations due to
physical health; and bodily pain), mental health domains (mental health,
reflecting primarily anxiety and depression; role limitations due to emo-
tional symptoms; and social functioning) and measures of ‘general
health’ and ‘vitality’ (or energy).
Of the 60 subjects, 26 (43%) were women. The patients’ mean age was
40.1 years (SD 10.6, range 19–67 years). Thirty patients (50%) were mar-
ried, 8 (13%) divorced and 22 (37%) were single.
The investigators’ hypothesis that OCD would most affect social rela-
tionships and instrumental role functioning (functioning in work, school
and homemaking) was confirmed: the subjects’ median scores for role
limitations due to emotional problems, social functioning and mental
health all fell below the 25th percentile for the US general population. In
contrast, the subjects’ median scores for the physical health domains
were at or above the general population medians. Greater severity of
OCD, as measured by the Yale–Brown Obsessive Compulsive Scale (Y-
BOCS, see Appendix 1, p. 183)12 was associated with poorer social func-
tioning, but not with role limitations due to emotional problems, even after
controlling for depression severity at baseline (as measured by the
Hamilton Depression Rating Scale).13 The absence of a relationship
between OCD severity and role limitations may reflect this scale’s limited
range and variance (raw score from 3 to 6) or the absence of extremely
severe OCD cases in the study group. Alternatively, the absence of a
relationship may have resulted from some patients’ ability to exert more
control over their symptoms at work or school than at home.
Unemployment was higher in the study group than in the US general

population (22% versus 9%) and 9 of the 13 unemployed subjects attrib-
uted their unemployment to the effects of OCD. Unlike the Obsessive
Compulsive Foundation survey respondents, many of whom were not in
treatment,7 these volunteers for a medication trial did not differ substan-
tially from the general US population in history of alcohol abuse (15% ver-
sus 11%) or of suicide attempts (3% versus 2%).14 As one would expect,
the median scores of the OCD subjects were higher than those of
patients with type 2 diabetes on all SF-36 physical health domains, and
lower on all mental health domains.
Although suggesting that OCD is associated with lower HRQL in cer-
tain domains, this study was limited by ascertainment bias (volunteers for
a medication trial who had to meet strict inclusion and exclusion criteria)
and by a relatively small sample size. In addition, the proportion of
women was greater in the study group than in the comparison groups,
which increased the differences in SF-36 scores. Finally, the validity of
the SF-36 in measuring HRQL in subjects with OCD has not been estab-
lished; many researchers prefer disorder-specific measurement tools.
Although many treatments are effective in relieving OCD symptoms,15
we know very little about how successful treatment affects the HRQL of
patients. Bystritsky and his colleagues have conducted the only study in
this area, examining change in HRQL in 30 consecutive, treatment-resis-
tant OCD patients after 6 weeks of treatment in a partial hospitalization
program.16 The patients’ mean age was 34 years (range 18–56 years)
and two-thirds were men. Only 13% were married. The investigators used
Lehman’s Quality of Life scale, which was developed to measure HRQL
in patients with schizophrenia.3 The scale provides objective and subjec-
tive (patient satisfaction) measures of activities, health, safety, living situ-
ation and of functioning related to family, social roles, work and finances.
After treatment, patient interviews indicated significant changes in the
objective measures reflecting activities, health and social functioning and
all of the subjective measures except family functioning. The changes in
quality of life showed little correlation with changes in the patients’ OCD
severity (Y-BOCS scores), suggesting that treatment effects on symp-
toms and on HRQL domains are not closely related. Further studies with
larger samples, appropriate control groups, different HRQL measures
and evaluation at varying time points are indicated.
Socioeconomic effects of OCD
The economic costs of OCD have been estimated in two studies. Dupont
and colleagues used a human capital methodology to estimate direct
and indirect costs of OCD in the USA.17 Taking lifetime prevalence data
from the Epidemiological Catchment Area (ECA) study,18 they estimated
Quality of life 55
that reduced or lost economic productivity for individuals affected by

OCD was $5.9 billion in 1990, or 70.4% of OCD’s total economic cost.
They also estimated a 2% suicide rate for individuals with OCD, resulting
in a 1990 loss to the US economy of $255 million. This 2% estimate may
be low. In a separate analysis of the ECA data, Hollander and his col-
leagues19 found that individuals with comorbid OCD (OCD accompanied
by other psychiatric disorders) had a 15% rate of suicide attempts, while
those with uncomplicated OCD had a rate of 3.6%. Extrapolating the pro-
portion of attempts that would be repeated over a lifetime and result in
eventual success cannot, of course, be done with much precision.
Leon and colleagues derived other measures of the OCD’s social costs
from the ECA data.20 They found higher unemployment rates in adult men
with OCD compared to individuals with no Axis I disorder (45% versus
20%); the proportion of individuals who had been unemployed for at least
5 years was much higher (18% versus 5%). Unemployment rates for
women with OCD were also elevated, but less dramatically. Individuals
with OCD were receiving disability payments at far higher rates than indi-
viduals with no Axis I disorder (23% versus 5% for men, and 13% versus
4% for women).
Impact of OCD on marital relationships and the family
Most studies,7,21–23 but not all,9 have found that patients with OCD have
lower marriage rates than the general population (80.6% for women, 73.2%
for men).24 In the ECA survey data, individuals with OCD had higher rates
of divorce and separation than individuals without OCD.2 Whether the
severity of OCD symptoms or particular symptom patterns such as hoard-
ing or religious obsessions have a greater impact on marriage rates has
not been determined. Marital maladjustment or dissatisfaction has been
reported in nearly half of married OCD sufferers.25,26 Only large-scale, con-
trolled studies can determine whether these rates are higher than those in
the general population. One study suggests they may not be.27
In my experience, OCD often diminishes the quality of family relation-
ships. The person with the disorder may ask family members, for exam-
ple, to avoid ‘contaminated’ objects or furniture in the home or to shower
and wash all clothes after exposure to ‘contaminated’ outside areas, to
aid in checking that all the doors and windows are locked and that all
appliances have been unplugged before going to bed each night, or to
provide repeated reassurances that no dangerous situation exists. The
patient may forbid family members to use a bathroom or may fill the
house with hoarded items so that most rooms become unusable.28–30 If
family members fail to comply with these demands, the patient may
erupt in anger or intense anxiety and subject the family to very unpleas-
ant verbal abuse. Family members, especially parents, may blame
themselves for the disorder, or feel guilty if their behavior increases the
sufferer’s anxiety or depression.
Despite their methodological limitations, the studies of the impact of
OCD on family relationships and family members all report a substantial
adverse effect. In a survey of 419 Obsessive Compulsive Foundation
members, 73% reported interference with family relationships.31 Nearly
all family members (85%) were bothered by the respondent’s OCD
rituals.32 In a study using a semistructured interview to evaluate the
accommodation to OCD by the family members of 34 OCD patients,
more than one-third of the family members had modified family routines
because of the patient’s symptoms and more than half reported that
accommodating to these symptoms had caused at least moderately
intense distress.28
More detail is provided by a study of 19 families with an adult member
with OCD, but the small sample size necessitates caution in viewing the
results.33 Disrupted family and social life was reported by more than half
of spouses, and anger and frustration, family conflicts, the patient’s
depression and marital difficulties disturbed nearly half. More than one-
third mentioned sexual difficulties, guilt and fatigue. Compared with well-
matched control families, the OCD families had lower scores on all seven
scales of a family assessment measure (problem-solving, communica-
tion, roles, behavior control, affective responsiveness, affective involve-
ment and general functioning). The OCD families scored in the
‘unhealthy’ range significantly more often on scales measuring communi-
cation, affective involvement and general functioning.
Another study of the family burden of OCD utilized structured inter-
views with 32 key relatives (primarily spouses or parents) of 32 adult
patients with OCD.34 Moderate or severe burden was reported by more
than one-third in the form of (for example) difficulty taking trips or holi-
days, poor social relationships (due entirely to the patient’s difficulties, in
half of those interviewed) and neglect of hobbies. More than half of the
relatives cited ‘Feeling of having given up leading one’s life as wanted’
(58%), ‘Feeling of not being able to stand the situation any longer’ (68%),
and ‘crying or depressive feelings’ (84%). The authors concluded that
OCD imposes a family burden similar to that imposed by major depres-
sion or schizophrenia.
How treatment of OCD affects the quality of life of patients’ family mem-
bers has not been studied. However, a study by Emmelkamp and col-
leagues suggests some benefit.25 Treatment reduced the partners’
anxiety, anger and marital dissatisfaction.
The detrimental effects of OCD on family relationships and social role
functioning may create negative feedback loops. For example, sufferers’
rates of help-seeking and degree of cooperation with treatment could be
adversely affected by poor interpersonal and familial relationships or
impaired ability to meet social role responsibilities. The resulting absent
Quality of life 57
or inadequate treatment would perpetuate the illness. Conversely, family

education, family support groups and participation in the patient’s treat-
ment may increase the likelihood of a favorable outcome. The fragmen-
tary data available are consistent with these hypotheses.29,35,36
Considerations for future research
Because little is known, there is much yet to learn. Future studies could
profitably investigate:
• The effects of OCD on HRQL in large samples of affected individuals.
Patients in treatment should be distinguished from individuals in the
community with OCD, since many of those who have not sought treat-
ment may have milder forms of the disorder.4,5
• How the effects of OCD on HRQL vary with patients’ gender, age at
onset, symptom severity, symptom type (e.g. obsessions only, obses-
sions and compulsions, hoarding versus cleaning versus checking to
prevent terrible consequences), and comorbid psychiatric conditions.
For example, the effects on women, who are frequently expected to
fulfill homemaking or mothering roles, may well differ from those on
men, who are usually expected to enter the workforce. Individuals
whose developmental years were substantially affected by the pres-
ence of OCD may exhibit different HRQL effects than those whose
OCD began in adulthood. Individuals with obsessions only may have
been more successful in hiding their disorder, with lesser effects on
some HRQL domains.
• The degree to which pharmacotherapies and cognitive-behavioral
therapies reverse adverse effects of OCD on particular domains of
HRQL. Is combined therapy more effective with regard to any
domains? How quickly does treatment reverse OCD’s adverse effects
on HRQL? One would expect symptoms to improve sooner than inter-
personal relationships and vocational performance, for example.
• The costs of attaining various degrees of improvement in HRQL
domains, as incurred by the affected individual, the family, the individ-
ual’s health plan and society at large. Once costs to the interested
parties have been identified, they can be weighed against the benefits
each party reaps. Placing an economic value on many HRQL benefits,
however, will require input from several disciplines since they have no
widely agreed monetary value.
Methodological considerations
The HRQL instruments that deserve serious consideration in future stud-

ies include the SF-36, Lehman’s Quality of Life scale and others that have
been commonly used and validated in other populations: the EuroQol,37

WHOQOL,1 Nottingham Health Profile,38,39 Quality of Well-Being Scale,26
the Social Adjustment Scale,40 and the five-item Work and Social Adjust-
ment Scale. The last-mentioned scale can be administered by interactive
telephone technology.41 The relative advantages and disadvantages of
these measures will vary with each study’s budget and aims.
In planning any study, attention to certain methodological questions
will enhance the value of the results. Experienced investigators recom-
mend attending to the assessor’s skill level (health-care professional,
social scientist or trained observer); who the respondent is (the patient, a
family member or another informant); the quality of life domains to be
assessed; the assessment method (interview, questionnaire or diary);
whether to use generic or disease-specific instruments; the time-frame
encompassed; and the reliability, validity and sensitivity of the measures
utilized.42 These issues and findings with regard to other mental disorders
are discussed elsewhere.2,43
Conclusion
The available data suggest that OCD substantially and adversely affects
the HRQL of sufferers and their families. Even in the absence of a con-
sensus regarding how to conceptualize or measure HRQL, studies
should be designed to further delineate and quantify the suffering and
impairment associated with OCD and the costs, benefits and limitations
of treatment.
References
1 Skevington SM, Bradshaw J, Sax- disorder in the epidemiological

ena S, Selecting national items for catchment area study, Am J Psy-
the WHOQOL: Conceptual and chiatry (1997) 154:826–31.
psychometric considerations, Soc 5 Degonda M, Wyss M, Angst J,
Sci Med (1999) 48:473–87. The Zurich Study XVIII. Obses-
2 Katschnig H, Freeman H, Sarto- sive-compulsive disorders and
rius N, Quality of Life in Mental syndromes in the general popula-
Disorders. (John Wiley: Chich- tion, Eur Arch Psych Clin Neu-
ester, 1997). rosci (1993) 243:16–22.
3 Lehman AF, Measurement of 6 Stein DJ, Roberts M, Hollander
quality of life among persons with E et al, Quality of life and phar-
severe and persistent mental dis- maco-economic aspects of
orders, Soc Psych Psychiatr Epi- obsessive-compulsive disorder.
demiol (1996) 31:78–88. A South African survey, S Afr
4 Nelson E, Rice J, Stability of diag- Med J (1996) 8(suppl. 12):
nosis of obsessive-compulsive 1579–85.
Quality of life 59
7 Hollander E, Stein D, Kwon JH et hospitalization program, Psychiat

al, Psychosocial function and Serv (1999) 50:412–14.
economic costs of obsessive- 17 Dupont RL, Rice DP, Shiraki S et
compulsive disorder, CNS Spec- al, Economic costs of obsessive-
trums (1997) 2:16–25. compulsive disorder, Med Interf
8 US Bureau of Census, Statistical (1995) 8:102–9.
Abstract of the United States: 18 Karno M, Golding JM, Sorenson
1995, 115th edn (US Government SB et al, The epidemiology of
Printing Office: Washington DC, obsessive-compulsive disorder in
1995). five US communities, Arch Gen
9 Koran LM, Thienemann ML, Dav- Psychiatry (1988) 45:1094–9.
enport R, Quality of life for 19 Hollander E, Greenwald S, Neville
patients with obsessive-compul- D et al, Uncomplicated and
sive disorder, Am J Psychiatry comorbid obsessive-compulsive
(1996) 153:783–8. disorder in an epidemiologic
10 Ware JE, Snow KK, Kosinski M et sample, Depress Anx
al, SF-36 Health Survey Manual (1996/1997) 4:111–19.
and Interpretation Guide (New 20 Leon AC, Portera L, Weissman
England Medical Center, Health MM, The social costs of anxiety
Institute: Boston, 1993). disorders, Br J Psychiatry (1995)
11 McHorney CA, Ware JE, Raczek 166(suppl. 27):19–22.
AE, The MOS 36-item Short-Form 21. Hafner RJ, Anxiety disorders. In:
Health Survey (SF-36). II: Psycho- Falloon IRH, ed., Handbook of
metric and clinical tests of validity Behavioral Family Therapy (Guil-
in measuring physical and mental ford Press: New York 1988),
health constructs, Med Care 203–30.
(1993) 31:247–63. 22 Stecketee G, Social support and
12 Goodman WK, Price LH, Ras- treatment outcome of obsessive
mussen SA et al, The Yale-Brown compulsive disorder at 9-month
Obsessive Compulsive Scale, I: follow-up, Behav Psychother
development, use, and reliability, (1993) 21:81–95.
Arch Gen Psychiatry (1989) 23 Steketee G, Grayson JB, Foa EB,
46:1006–11. Obsessive-compulsive disorder:
13 Hamilton M, Development of a differences between washers and
rating scale for primary depres- checkers, Behav Res Ther (1985)
sive illness, Br J Soc Clin Psychol 23:197–201.
(1967) 6:278–96. 24 US Bureau of Census, Statistical
14 Markowitz JS, Weissman MM, Abstract of the United States:
Ouellette R, Quality of life in panic 1996, 116th edn. (US Govern-
disorder, Arch Gen Psychiatry ment Printing Office: Washington
(1989) 46:984–92. DC, 1996).
15 Koran LM, Obsessive-compulsive 25 Emmelkamp PMG, de Haan E,
disorder. In: Obsessive-Compul- Hoogduin CAL, Marital adjust-
sive and Related Disorders in ment and obsessive-compulsive
Adults: A Comprehensive Clinical disorder, Br J Psychiatry (1990)
Guide (Cambridge University 156:55–60.
Press: Cambridge, 1999). 26 Pyne JM, Patterson TL, Kaplan
16 Bystritsky A, Saxena S, Maidment RM et al, Assessment of the qual-
K et al, Quality-of-life changes ity of life of patients with major
among patients with obsessive- depression, Psych Serv (1997)
compulsive disorder in a partial 48:224–30.
27 Balslev-Olesen T, Geert-Jor- compulsive disorder. In: Swinson

gensen E, The prognosis of RP, Antony MM, Rachman S et al,
obsessive-compulsive disorder, eds, Obsessive Compulsive Dis-
Acta Psychiatr Scand (1989) order: Theory, Research, and
34:232–41. Treatment, (Guilford Press: New
28 Calvocoressi L, Lewis B, Harris M York, 1998), 120–40.
et al, Family accommodation in 37 Johnson JA, Coons SJ, Ergo A et
obsessive-compulsive disorder, al, Valuation of EuroQOL (EQ-5D)
Am J Psychiatry (1995) 152: health states in an adult US sam-
441–3. ple, Pharmacoeconomics (1998)
29 Mehta M, A comparative study of 13:421–33.
family-based and patient-based 38 Hunt SM, McKenna SP, McEwen
behavioural management in J et al, The Nottingham Health
obsessive-compulsive disorder, profile: subjective health status
Br J Psychiatry (1990) 157:133–5. and medical consultations, Soc
30 Shafran R, Ralph J, Tallis F, Sci Med (1981) 15A:221–9.
Obsessive-compulsive symptoms 39 Lukkarinen H, Hentinen M,
and the family, Bull Menninger Assessment of quality of life with
Clin (1995) 59:472–9. the Nottingham Health Profile
31 Hollander E, Kwon K, Won JH et among women with coronary
al, Obsessive-compulsive and artery disease, Heart Lung (1998)
spectrum disorders: overview and 27:189–99.
quality of life issues, J Clin Psy- 40 Weissman MM, Prusoff BA,
chiatry (1996) 57(suppl. 8):3–6. Thompson WD et al, Social
32 Black DW, Gaffney G, Schlosser adjustment by self-report in a
S et al, The impact of obsessive- community sample and in psychi-
compulsive disorder on the fam- atric outpatients, J Nerv Ment Dis
ily: preliminary findings, J Nerv (1978) 166:317–26.
Ment Dis (1998) 186:440–2. 41 Mundt JC, Kobak KA, Greist JH
33 Cooper M, Report on the findings et al, Work and social adjustment
of study of OCD family members, scale: an alternative quality-of-
OCD Newsl (1994) 8:1–2. life instrument. Poster presented
34 Magliano L, Tosini P, Guarneri M at the 39th Annual NCDEU Meet-
et al, Burden on the families of ing, Boca Raton, FL, 1–4 June
patients with obsessive-compul- 1999.
sive disorder: A pilot study. Eur 42 Aaronson NK, Quality of life
Psychiatry (1996) 11:192–7. assessment in clinical trials:
35 Leonard HL, Swedo SE, Lenane methodologic issues, Control Clin
MC et al, A 2- to 7-year follow-up Trials (1989) 10:195-208S.
study of 54 obsessive-compulsive 43 Gladis MM, Gosch EA, Dishuk
children and adolescents, Arch NM et al, Quality of life: expand-
Gen Psychiatry (1993) 50:429–39. ing the scope of clinical signifi-
36 Steketee G, Pruyn NA, Families of cance, J Consult Clin Psychol
individuals with obsessive- (1999) 67:320–31.
6
The role of genetic factors in OCD
David L Pauls
Obsessive compulsive disorder (OCD) is a serious, potentially debilitat-

ing psychiatric condition affecting both children and adults.1 Originally,
OCD was considered to be rare in the general population.2 However,
recent data suggest that it is a common disorder with lifetime prevalence
rates ranging from 1.9% to 3.3%.3 This estimate was obtained from data
collected using the Diagnostic Interview Schedule (DIS), a structured
interview that elicited information to establish DSM-III diagnoses.4
Furthermore, the lifetime prevalence rates of OCD in Canada, Puerto
Rico, Germany, Taiwan, Korea and New Zealand were essentially the
same as that reported in the USA. Rates ranged from 1.1% in Korea to
1.8% in New Zealand.
The influence of genetic factors has been suggested from the earliest
descriptions of the disorder. Evidence for the influence of genetic factors
has come from twin and family aggregation studies. Furthermore, drug
treatment and functional neuroimaging studies have added strength to
the genetic investigations by emphasizing the biochemical and biological
nature of the disorder. In addition, recent molecular genetic studies sug-
gest that specific genes may account for some of the variance in the
manifestation of OCD.
Twin studies
Twin studies have provided evidence for the role of genetic factors in
neuropsychiatric disorders.5 The twin method consists of comparing the
number of monozygotic (MZ) twins in which both members are affected
(i.e. the pair is concordant) with the number of dizygotic (DZ) twin pairs
concordant for the trait of interest. If the concordance of MZ twins is sig-
nificantly higher than the concordance of DZ twins, it is taken as evi-
dence for the contribution of genetic factors to the expression of the
disorder under study. The similarity between twins can also be
expressed as heritability. Heritability is defined as the proportion of
61
phenotypic variance due to additive genetic factors. This statistic is

descriptive but not predictive. A large heritability component does not
preclude substantial influences by environmental factors within the popu-
lation.6,7 It does, however, serve as an indicator of a potentially significant
biological etiology for a specific disorder.
In an early twin study of OCD completed in Japan, observed concor-
dance rates were 80% among ten pairs of MZ twins and 50% among four
pairs of DZ twins diagnosed as having ‘obsessional neurosis’.8 The small
sample size precludes any definitive conclusions, but the data are con-
sistent with a hypothesis of some genetic involvement.
In their review of the extant literature prior to 1986, Rasmussen and
Tsuang found that 63% (32/51) of MZ twins were concordant for OCD.9
When twins for whom zygosity was in doubt were eliminated from the
sample, 65% (13/20) were concordant for OCD. These MZ concordance
rates are similar to those reported for other affective and anxiety disor-
ders (see reference 5 for review). However, the results need to be inter-
preted with caution because no data from DZ twins were available for
comparison. Thus, it is not possible to determine the extent to which
genetic factors contribute to the expression of OCD from these data.
Several twin studies not included in the Rasmussen and Tsuang review
included data from DZ twins. Carey and Gottesman studied 15 MZ and
15 DZ twins ascertained from the Maudsley Twin Register.10 These twins
represented a consecutive series seen between 1910 and 1955. Each
twin pair was personally interviewed using a structured interview docu-
menting occurrence of psychiatric symptoms. This information was com-
bined with hospital notes to determine the final psychiatric status. The
investigators observed concordance rates of 87% and 47% for obsessive
symptoms in MZ and DZ twins respectively.
In a study of 32 MZ and 53 DZ same-sex Norwegian twins, Torgersen
investigated the concordance of anxiety disorders (including obsessive
compulsive disorder).11 The sample consisted of all twins born between
1910 and 1955 who were admitted for treatment of neurotic or borderline
psychotic disorders at any time before 1977. Each twin was interviewed
using a structured psychiatric interview which documented the lifetime
occurrence of psychiatric symptoms. As in the Carey and Gottesman
study, the interview data were combined with the hospital records to
make DSM-III lifetime diagnoses. Six DSM-III anxiety disorders were
examined: panic disorder, agoraphobia with and without panic, social
phobia, obsessive compulsive disorder, and generalized anxiety disorder
(GAD). No twins were concordant for the same DSM anxiety disorder.
Thus, the author examined concordances in the larger context of an ‘anx-
iety spectrum’. When the classification ‘all anxiety disorders except GAD’
was used to assigned affected status to the probands, the concordance
rate was 45% in MZ pairs compared with 15% in DZ pairs (p < 0.02). This
difference was not seen when considering GAD alone or for a proband
The role of genetic factors 63
diagnostic category of ‘all anxiety disorders’. The author argued that

these findings support the conclusion that genetic factors are important
for the manifestation of non-GAD anxiety disorders. Thus, because OCD
was included as part of the non-GAD anxiety disorder spectrum, genetic
factors important in the etiology of OCD would have contributed to the
finding of a higher MZ concordance.
Finally, Andrews et al administered structured psychiatric interviews to
186 MZ and 260 DZ twin pairs (446 pairs total) ascertained from the gen-
eral Australian Twin Registry.12,13 This study differs from those above in
that ascertainment was not based on psychiatric index cases. Lifetime
data for OCD, GAD, panic disorder, social phobia and major depressive
disorder were obtained. Concordance rates for MZ and DZ twins were
not significantly different for specific disorders. However, when the diag-
noses were combined into a single category of ‘neuroticism’, the MZ con-
cordances were significantly higher than those for the DZ twins (0.58 and
0.44 in female and male MZ twins, respectively, and 0.31, 0.27 and 0.33
in female, male and opposite-sex DZ twins, respectively). The data also
support the conclusion that genetic factors are important for the manifes-
tation of anxiety disorders in general.
The twin studies described above relied on categorical diagnoses. In
1984, Clifford and colleagues completed genetic analyses on data col-
lected from 419 unselected twin pairs who had been given the 42-item
version of the Leyton Obsessional Inventory (LOI).14 Multivariate genetic
analyses yielded separate heritability estimates of 44% for obsessional
traits (as defined by the 10-item trait scale of the LOI) and 47% for obses-
sional symptoms (as defined by the 32-item symptom scale). These
results support the earlier findings that genetic factors are important for
the expression of the specific symptoms necessary for a diagnosis of
OCD. They also support the notion that genetic factors influence the
development and expression of obsessive-compulsive personality traits.
These results suggest that the genetic factors important for symptoms
and traits are in part independent from each other.
In summary, these twin studies provide some support for the hypothe-
sis that genetic factors play a role in the manifestation of OCD. However,
it is not clear whether these factors are specific for OCD or whether OCD
is part of a broader, heritable anxiety spectrum. None of these studies
provides conclusive evidence, but rather each serves as an indicator of a
potentially significant genetic component in the etiology of OCD.
Family studies
A number of family studies on OCD and obsessional neurosis have been
reported over a period of six decades. Overall, the data demonstrate
that OCD is familial. Familial aggregation of a disorder is a necessary
consequence if it is genetically transmitted. On the other hand, demon-

stration of familial aggregation is not sufficient to infer that there is
genetic transmission. The family is the essential unit for transmitting not
only genes but also the environmental and cultural factors that influence
human behavioral phenotypes. These factors can have a large influence
on phenotypic development and outcome. An understanding of these
influences is crucial to the investigation of traits that typically have com-
plex causes. Thus, while genetics alone may not explain familial aggre-
gation of a disorder, demonstrating aggregation is an important step in
understanding whether genetic factors are important.
Family study paradigms consist of:
• ascertainment of index cases (probands) affected with the disorder
under investigation15,16
• estimation of the prevalence of the disorder among the biological rela-
tives of probands
• comparison of rates of illness in families with those seen in control
groups or in the general population.
The selection of an appropriate control group is essential. Control groups
may be ascertained as relatives of unaffected cases, or as relatives of indi-
viduals affected with an unrelated disorder, or as relatives of randomly
selected individuals from the general population. Population prevalence
provides an alternative comparison, provided that the data were collected
using similar (preferably identical) assessment instruments. Unfortunately,
in most instances this kind of population information is not available, hence
family-based control studies are necessary to obtain an appropriate com-
parison to determine whether a condition does run in families.
Two methods are used in determining the prevalence in relatives: the
family history method, and the direct interview or family study method.
Both methods endeavor to collect accurate symptom information on rela-
tives that will allow the assignment of a best-estimate diagnosis.17 The
family history method relies on a single informant (usually the proband or
the parent of a proband) to report diagnostic information on all first-
degree relatives. In contrast, the direct interview method relies on per-
sonal assessment of all first-degree relatives to obtain diagnostic
information. Because subjects sometimes fail to report symptoms in a
direct interview (as may be the case in OCD, where sufferers tend to be
secretive about their symptoms), the family history method can provide
information that would be unavailable by direct interview alone. On the
other hand, single informants may be unaware of specific symptoms in
their first-degree relatives, in which case the prevalence in first-degree
relatives may be underestimated; in this case, a direct interview offers an
opportunity to gather otherwise unattainable information. To overcome
the possible shortcomings of each method, both family history and direct
interview data should be combined to assign diagnoses.
Family history method

All family aggregation studies completed prior to 1980 relied on the fam-
ily history method. It is noteworthy that even using this method, the earli-
est studies demonstrated that obsessive compulsive illness was familial.
Lewis reported that out of 306 first-degree relatives of obsessive compul-
sive patients, 37 parents and 63 siblings displayed pronounced obses-
sional traits, yielding a rate of 32.7%.18 Brown found obsessional
neuroses in 3 out of 40 parents and 4 of 56 siblings of obsessive compul-
sive neurotics; a rate of 7.3% among first-degree relatives.19 Furthermore,
Kringlen reported that 50% of the parents of 91 obsessional patients
were ‘nervous’.20 Eighteen of the parents were diagnosed as obsessional
neurotics. In 1967, Rosenberg reported a study of 547 first-degree rela-
tives of 144 obsessional neurotics.21 He reported an increased rate of
psychiatric illness among first-degree relatives of obsessional neurotics,
but there was no significant increase of obsessive compulsive disorder
among those relatives. It is noteworthy that Rosenberg required that a rel-
ative be hospitalized in order to be included as affected. Similarly, Insel
et al found no OCD among parents of 27 individuals with OCD;22 how-
ever, when 20 parents were administered the Leyton Obsessional Inven-
tory, 3 were found to have obsessive thoughts about contamination that
were not recognized as problematic by their offspring proband. No infor-
mation on siblings was provided. In 1986, Rasmussen and Tsuang
described a sample of 44 patients who met DSM-III criteria for OCD.9
Four of the 88 (4.5%) parents met the full criteria for OCD, and another 10
(11.4%) had significant obsessive compulsive traits that were not
egodystonic. Combining the two groups into one obsessional category,
15.9% of the parents of OCD patients were affected.
Direct interview method

McKeon and Murray used a modified strategy to study first-degree rela-
tives of 50 obsessive compulsive patients and those of matched
controls.23 These investigators requested that all relatives complete the
LOI, and those who had high scores were interviewed directly. Although
these relatives had a significantly higher rate of mental illness, there was
only one who met criteria for obsessive compulsive neurosis. Thus, these
investigators did not find any evidence to suggest that OCD was familial.
One possible shortcoming of this study is the fact that individuals can
have fairly low scores on the LOI by virtue of having only a few obses-
sions or compulsions, but those obsessions and compulsions can cause
significant distress. Thus, it is possible that some affected relatives may
have been missed in the ascertainment scheme employed.
Eight more recent studies of OCD directly interviewed all available
relatives and used standard diagnostic criteria.24–31 Findings from these
studies provide further support for the hypothesis that there is a familial
component important for the expression of some forms of OCD. Three of
the studies focused on families of children with OCD,24–26 whereas the
other five reported data from families of adult probands.27–31
Lenane and colleagues studied 145 first-degree relatives of 46 chil-
dren and adolescents with severe primary OCD who were consecutive
admissions to a National Institute of Mental Health (NIMH) study of
severe primary childhood OCD.24 All parents and relatives were person-
ally interviewed with structured psychiatric interviews. All diagnoses were
based on DSM-III criteria. Seventeen per cent of the parents met criteria
for OCD. No control group was examined.
Lenane and colleagues also examined the relationship between the
probands’ primary OCD symptoms and those of their respective rela-
tives. They found no consistent pattern between parents and children,
nor between older and younger siblings. Hence, a simple modeling
hypothesis whereby OC symptoms are observed and learned by suscep-
tible younger relatives was not supported by the data.24
A second study of childhood OCD interviewed the parents of 21 clini-
cally referred children and adolescents with obsessive compulsive disor-
der.25 Four of 42 (9.5%) parents received a DSM-III diagnosis of OCD. No
information concerning rates of diagnosis in siblings was given. Inter-
viewers and raters were not blind to the status of the proband and no
control group was examined.
Finally, a third study examined 171 first-degree relatives of 54 childhood
probands who were part of a drug treatment trial at NIMH.26 Forty-six of
these probands and their families had been studied previously by Lenane
et al.24 The later study was a 2-year to 7-year follow-up evaluation of those
probands and their families. All diagnoses were made using DSM-III-R cri-
teria. Thirteen per cent of all first-degree relatives met criteria for OCD.
Bellodi et al studied the families of 92 adult patients with OCD.27 These
patients were consecutive admissions for primary OCD at a specialty
anxiety disorders clinic in Milan. All first-degree relatives were evaluated
by either direct interview or family history. The rate of OCD among par-
ents and siblings was only 3.4%. Although this rate was considerably
lower than other published studies, it nevertheless represented a four-
fold increase over population prevalence estimates for the Italian popula-
tion. Furthermore, when probands were separated on the basis of age at
onset (with ‘early onset’ defined as occurring at or up to 14 years of age),
the frequency of OCD was significantly higher among the relatives of
early-onset probands. The morbid risk for OCD among relatives of the 21
early-onset probands was 8.8% compared with 3.4% among the relatives
of 71 later-onset probands. The number of relatives in each proband
onset category was not given. As in previous studies, this group of inves-
tigators did not ascertain or assess a comparison sample.
Nicolini et al studied the families of 27 OCD probands ascertained
through the Mexican Institute of Psychiatry in Mexico City.28 Probands

and all available first- and second-degree relatives were evaluated by
direct interview, and unavailable relatives were evaluated by the family
history method. All diagnoses were made with DSM-III-R criteria. A total
of 268 first-degree relatives and 187 second-degree relatives were evalu-
ated. Thirteen first-degree relatives received an OCD diagnosis, for a fre-
quency of 4.9%; this was significantly different at the p < 0.05 level from
the population prevalence of 1.8% in the USA.3 The validity of this com-
parison rests on the assumption that the prevalence of OCD is similar in
Mexico and the USA. The cross-national study suggests that this
assumption is plausible, but it has not been confirmed.
A significant methodologic weakness of the five family studies just
described was the lack of an appropriate comparison sample. Thus, it is
not possible to determine whether the frequency of OCD observed
among the family members in these studies was significantly higher than
would be observed by these same investigators employing the same
diagnostic methods in an independent sample of comparison subjects.
Although the frequency of OCD in the families of affected probands
could be compared with the population prevalence, the epidemiological
investigations conducted to estimate that prevalence should have been
done in the same geographic regions using identical assessment meth-
ods to ensure that the samples were comparable.
In contrast to these five studies, three more recent studies did include
control groups. Black et al reported the findings from a study of 120 first-
degree relatives of 32 OCD probands and 129 relatives of 33 psychiatri-
cally normal controls.29 Assessment of relatives was through direct
structured interviews. Furthermore, the interviewer was blind to the
proband’s diagnostic status. All diagnoses were made using DSM-III cri-
teria. The age-corrected morbid risk of OCD was 2.5% among relatives of
OCD probands compared with 2.3% in relatives of controls; both values
agree with the Epidemiology Catchment Area lifetime prevalence for
OCD and thus provide no evidence that OCD is familial. However, the
risk of a more broadly defined OCD was increased among the parents of
OCD probands (15.6%) when compared with parents of normal
individuals (2.9%).
A possible shortcoming of the Black study is that the investigators
used only direct interview data to determine affected status. That is, they
did not use all available information to assign diagnoses. In most family
studies, the best estimate diagnostic process is used to assign the diag-
nosis to all probands and relatives.17 This procedure includes direct inter-
view information as well as family history data collected from multiple
informants in the family. As noted above, individuals with OCD can be
quite secretive about their symptoms, and in a direct interview might
deny OC symptomatology, particularly if they had never sought help for
their symptoms. It is noteworthy that Black and colleagues recorded that
a number of family members were reported to have OC symptomatology

by their relatives. Thus, if the direct interview and family history data had
both been used to obtain diagnoses, it is likely that the recurrence risk for
OCD among first-degree relatives would have been higher than among
control relatives.
In a second controlled study 100 OCD probands, their 466 biological
first-degree relatives and 113 comparison subjects were examined.30 The
113 control group members were first-degree relatives of 33 psychiatri-
cally unaffected subjects. All available first-degree relatives were inter-
viewed directly and family history data were collected for all first-degree
relatives from the interviewed participants. Best estimate diagnoses were
assigned according to DSM-III-R criteria using all available clinical data.
The frequency of OCD was significantly increased among relatives of
OCD probands (10.3%) compared with control subjects (1.9%,
p < 0.005).
Finally, Nestadt and colleagues studied 343 first-degree relatives of 80
OCD probands and 300 first-degree relatives of 73 control subjects.31
Subjects were interviewed directly by clinicians using structured inter-
views. Additionally, a knowledgeable informant was interviewed about
each subject. Consensus DSM-IV diagnoses were made using all avail-
able clinical data. Significant odds ratios were found for all definitions of
the affected phenotype, indicating that first-degree relatives of cases met
criteria for OCD-related phenotypes more often than first-degree relatives
of controls. The actual risks to relatives were almost identical to the
results reported by Pauls et al.30 In general, using a more stringent crite-
rion for affection status resulted in a more significant odds ratio. Interest-
ingly, a stronger familial risk was found for obsessions than for
compulsions.
It should be noted that in the Nestadt study as well as that of Pauls and
colleagues, approximately half of the probands did not have any other
relative with OCD; that is, they were isolated cases in their families. This
pattern of familiality has also been observed in three other studies.28,32,33
Thus, OCD appears to be a heterogeneous condition. Some cases are
familial and others appear to have no family history of either OCD or other
related conditions.
These studies of OCD probands and their relatives cumulatively pro-
vide strong evidence that some forms of OCD are familial. Taken
together, the family and twin data reviewed here provide strong evidence
that genetic factors play an important role in the manifestation of some
forms of OCD.
Segregation analyses
Once familial aggregation of a disorder is established, a logical next step
is to determine if the patterns of aggregation can be explained by
Mendelian genetic models. Segregation analysis accomplishes this by
examining the goodness-of-fit of genetic and non-genetic models to the
observed data, and rejecting the models that do not explain the data
well. Although segregation studies cannot prove the existence of genes,
if the analyses reveal that the patterns within families are consistent with
simple modes of inheritance, the results can be taken as evidence for the
importance of genes in the etiology of the disorder. Three segregation
analysis studies of nuclear families ascertained through a proband with
OCD have been reported.
Nicolini and colleagues performed segregation analyses on data col-
lected from 24 OCD families ascertained through the UCLA Child Psychi-
atry Clinic.34 Eleven of the 24 probands had a positive family history of
OCD. All available first-degree relatives were directly interviewed, with
family history information used for unavailable relatives. Segregation
analyses were performed including all affected individuals with a diagno-
sis of OCD, chronic motor tics, or Tourette’s disorder. These investigators
were unable to statistically reject either an autosomal dominant or autoso-
mal recessive model.
More recent segregation analyses of a sample of 107 Italian families
also provide evidence for genetic transmission of OCD.35 Using regres-
sive logistic models to test for possible models of genetic transmission,
the authors determined that an autosomal dominant genetic model pro-
vided the best explanation for the pattern of transmission of OCD in these
families. However, while the most parsimonious results suggested a sin-
gle autosomal locus, other major gene solutions could also adequately
explain the observed familial patterns.
Finally, Alsobrook et al reported the results of complex segregation
analyses of 100 families ascertained through 100 adults with OCD.36
Complex segregation analyses were completed using the computer pro-
gram POINTER.37 Using the entire data set and including as affected
those relatives with a diagnosis of OCD, only the model of no transmis-
sion could be rejected. However, the polygenic model was nearly
rejected. The lack of definitive results with the total sample could be due
to the fact that, as noted above, approximately half of the families in this
sample did not have any relatives affected with OCD.
Given these findings, these investigators undertook segregation analy-
ses of the subset of families in which there were at least two individuals
affected with DSM-III-R OCD. A total of 52 families were included in these
analyses. Only relatives with OCD were included as affected. After
correcting for the additional ascertainment bias introduced by selecting
only familial cases of OCD, the models of no transmission, polygenic
inheritance and single locus inheritance were all rejected. The best
explanation of the patterns of transmission in these families was a genetic
model that included genes of major effect as well as a polygenic back-
ground (the ‘mixed model’ of inheritance).
The results of all segregation analyses demonstrate that the transmis-
sion of OCD in families is difficult to model. This is not surprising given
the clinical heterogeneity observed and the variability of family patterns
that is evident from the several family studies published. However, in
families in which the disorder is clearly familial (i.e. families in which there
are at least two individuals with OCD), the results suggest a less complex
mode of inheritance. The pattern in these families is consistent with a
mixed model of transmission. The mixed model specifies a gene of major
effect on a multigenic background. Thus, it is possible that there are sev-
eral genes that influence components of OCD. Investigation of these fac-
tors in families with at least two affected individuals will allow a better
evaluation of the underlying genetic and biological factors that might be
important.
Candidate gene studies
Pharmacological and neurobiological studies have implicated several

central neurotransmitter systems in the pathophysiology of OCD and
related conditions. The strongest pharmacological evidence concerns
the serotonergic system and the well-established efficacy of potent sero-
tonin reuptake inhibitors in the treatment of OCD.38,39 However, other sys-
tems have also been implicated. Specifically, central dopaminergic and
opioid systems seem to be important in the expression of some forms of
OCD.39–42 More recently, several studies have implicated two closely
related neuropeptides, arginine vasopressin (AVP) and oxytocin (OT) in
the pathobiology of some forms of OCD.43–46 Both AVP and OT have been
implicated in the manifestation of memory, grooming, and sexual and
aggressive behaviors.47
Given the apparent involvement of the serotonin and dopamine sys-
tems in OCD, a number of studies have examined several different
genetic loci as possible candidate genes important for the manifestation
of OCD. Genes examined include those coding for the serotonin trans-
porter, the 5-HT2A, 5HT2C, DRD2, DRD3 and DRD4 receptors and the
COMT locus. The results have been mixed, with some studies suggesting
an association with OCD and others failing to replicate the findings.
The most recent family-based association study examined the associa-
tion between OCD and the 5-HT1D␤ autoreceptor gene.59 This receptor is
particularly interesting in OCD, as studies have shown that the 5-HT1D␤
selective ligand sumatriptan may improve symptoms in OCD patients
resistant to conventional pharmacotherapy.60 Results of a transmission
disequilibrium test showed a preferential transmission of the G allele of

the G861C polymorphism of the 5-HT1D␤ locus to OCD affected subjects
(z ⫽ 1.524, p < 0.01).61,62 As with the previous results, these findings
need to be replicated on larger samples. If confirmed, the 5-HT1D␤ recep-
tor gene will be implicated in either the pathogenesis of OCD, or in the
mechanism of the pharmacological response.
Given the complexity of the OCD phenotype, it is unlikely that any of
these genes would have a major effect on the manifestation of the disor-
der. Given that current therapeutic agents appear to have their major
influence on the serotonin and dopaminergic systems, it is possible that
some of these genes might be important for effective treatment, but that
does not necessarily imply that those same genes are involved in the
etiology of OCD.
Future work
Because many published reports of genetic analyses suggest that some

forms of OCD have a genetic basis, genetic linkage studies are war-
ranted as the next step in our understanding of the inheritance of the dis-
order. Genetic linkage studies provide a powerful method for confirming
the hypotheses of genetic involvement, because linkage results can
demonstrate the existence of a genetic locus and help clarify the pattern
of inheritance. The localization of genes responsible for the expression of
OCD will be a major step forward in our understanding of the genetic and
biological risk factors important for the expression of this disorder. In
addition, this work will potentially allow the identification of non-genetic
factors associated with the manifestation or the amelioration of the symp-
toms of the disorder.63 On one hand, the identification of a linked marker
will permit the design of more incisive studies to illuminate the biochemi-
cal basis of OCD by examination of the gene product and its impact on
the manifestation of the disorder. On the other hand, by controlling for
genetic factors it will be possible to document more carefully the non-
genetic factors important for the expression of obsessions and compul-
sions. The ability to make use of genetic linkage and other aspects of
genetic studies to design and carry out a study of non-genetic etiologic
factors of a psychiatric illness is a significant methodological advance-
ment that has not been possible heretofore.
Acknowledgements
This work was supported in part by grants NS-16648, MH-49351 and
MH-00508 (an NIMH Research Scientist Award to Dr Pauls).
References
1 Calvocoressi L, Libman D, Vegso and obsessive disorders. In Klien
SJ et al, Global functioning of DF, Rabkin J, eds, Anxiety: New
inpatients with obsessive- Research and Changing Con-
compulsive disorder, schizophre- cepts (Raven Press: New York,
nia, and major depression, 1981) 117–36.
Psychiatr Serv (1998) 49:379–81.
11 Torgersen S, Genetic factors in
2 American Psychiatric Association anxiety disorder, Arch Gen Psy-
Committee on Nomenclature and chiatry (1983) 40:1085–9.
Statistics, Diagnostic and Statisti-
cal Manual of Mental Disorders, 12 Andrews G, Stewart G, Allen R,
3rd edn (American Psychiatric Henderson AS, The genetics of
Association: Washington, DC, six neurotic disorders: a twin
1980). study, J Affect Disord (1990) 19:
23–9.
3 Karno M, Golding JM, Sorenson
SB, Burnam MA, The epidemiol- 13 Andrews G, Stewart G, Morris-
ogy of obsessive-compulsive dis- Yates A, Holt P, Henderson AS,
order in five U.S. communities, Evidence for a general neurotic
Arch Gen Psychiatry (1988) 45: syndrome, Br J Psychiatry (1990)
1084–99. 157:6–12.
4 Robins LN, Helzer JE, Croughan 14 Clifford CA, Murray RM, Fulker
J, Ratcliff KS, National Institute of DW, Genetic and environmental
Mental Health Diagnostic Inter- influences on obsessional traits
view Schedule: its history, char- and symptoms, Psychol Med
acteristics, and validity, Arch Gen (1984) 14:791–800.
Psychiatry (1981) 38:381–9.
15 Khoury MJ, Beaty TH, Cohen BH,
5 National Institute of Mental Fundamentals of Genetic Epi-
Health’s Genetics Workgroup, demiology. Monographs in Epi-
Genetics and Mental Disorders demiology and Biostatistics,
(National Institute of Mental Health, vol. 19 (Oxford University Press:
Washington, DC, 1998) 1–82. New York, 1993).
6 Vogel F, Motulsky AG, Human
Genetics, 2nd edn (Springer: 16 Weissman MM, Merikangas KR,
New York, 1986). John K, Wickramaratne P, Prusoff
BA, Kidd KK, Family-genetic
7 Lewontin R, Comment on an erro- studies of psychiatric disorders,
neous conception of the meaning Arch Gen Psychiatry (1986) 43:
of heritability, Behav Genet (1976) 1104–16.
6:373–4.
17 Leckman JF, Sholomskas D,
8 Inouye E, Similar and dissimilar
Thompson WD, Belanger A,
manifestations of obsessive-
Weissman MM, Best estimate of
compulsive neurosis in monozy-
lifetime psychiatric diagnosis: a
gotic twins, Am J Psychiatry
methodologic study, Arch Gen
(1965) 121:1171–5.
Psychiatry (1982) 39:879–83.
9 Rasmussen SA, Tsuang MT, Clini-
cal characteristics and family his- 18 Lewis A, Problems of obsessional
tory in DSM-III obsessive- illness, Proc Roy Soc Med (1935)
compulsive disorder, Am J Psy- 29:325–36.
chiatry (1986) 143:317–22. 19 Brown FW, Heredity in the psy-
10 Carey G, Gottesman II, Twin and choneuroses, Proc Roy Soc Med
family studies of anxiety, phobic (1942) 35:785–90.
20 Kringlen E, Obsessional neu- 30 Pauls DL, Alsobrook JP, Good-

rotics: a long term follow-up, Br J man W, Rasmussen S, Leckman
Psychiatry (1965) 111:709–22. JF, A family study of obsessive
21 Rosenberg CM, Familial aspects compulsive disorder, Am J Psy-
of obsessional neurosis, Br J Psy- chiatry (1995) 152:76–84.
chiatry (1967) 113:405–13. 31 Nestadt G, Samuels J, Riddle M
22 Insel T, Hoover C, Murphy DL, et al, A family study of obsessive-
Parents of patients with obsessive compulsive disorder, Arch Gen
compulsive disorder, Psychol Psychiatry (2000) 57:358–63.
Med (1983) 13:807–11. 32 Eapen V, Robertson MM, Also-
23 McKeon P, Murray R, Familial brook JP, Pauls DL, Obsessive
aspects of obsessive-compulsive compulsive symptoms in Gilles
neurosis, Br J Psychiatry (1987) de la Tourette’s syndrome and
151:528–34. obsessive compulsive disorder:
24 Lenane MC, Swedo SE, Leonard differences by diagnosis and
H, Pauls DL, Sceery W, Rapoport family history, Am J Med Genet
J, Psychiatric disorders in first (1997) 74:432–8.
degree relatives of children and 33 Cavallini MC, Pasquale L, Bellodi
adolescents with obsessive- L, Smeraldi E, Complex segrega-
compulsive disorder, J Am Acad tion analysis for obsessive com-
Child Adolesc Psych (1990) pulsive disorder and related
29:407–12. disorders, Am J Med Genet (Neu-
25 Riddle MA, Scahill L, King R et al, ropsych Genet) (1999) 88:38–43.
Obsessive compulsive disorder in 34 Nicolini H, Hanna G, Baxter L,
children and adolescents: phe- Schwartz J, Weissbecker K,
nomenology and family history, J Spence MA, Segregation analysis
Am Acad Child Adolesc Psych of obsessive compulsive and
(1990) 29:766–72. associated disorders. Preliminary
26 Leonard HL, Lenane MC, Swedo results, Urs Medic (1991) 1:25–8.
SE, Rettew DC, Gershon ES,
35 Cavallini MC, De Bella D,
Rapoport JL, Tics and Tourette’s
Pasquale L, Henin M, Bellodi L,
disorder: A 2- to 7-year follow-up
5HT2C CYS23/SER23 polymor-
of 54 obsessive-compulsive chil-
phism is not associated with
dren, Am J Psychiatry (1992) 149:
obsessive-compulsive disorder,
1244–51.
Psychiatr Res (1998) 77:97–104.
27. Bellodi L, Sciuto G, Diaferia G,
Ronchi P, Smeraldi E, Psychiatric 36 Alsobrook JP, Leckman JF,
disorders in the families of Goodman WK, Rasmussen SA,
patients with obsessive- Pauls DL, Segregation analysis of
compulsive disorder, Psychiatr obsessive-compulsive disorder
Res (1992) 42:111–20. using symptom-based factors,
Am J Med Genet (Neuropsych
28 Nicolini H, Weissbecker K, Mejia
Genet) (1999) 88(6):669–75.
JM, Sanchez de Carmona M,
Family study of obsessive- 37 Lalouel JM, Rao DC, Morton NE,
compulsive disorder in a Mexican A unified model for complex seg-
population, Arch Med Res (1993) regation analysis. Am J Hum
24(2):193–8. Genet (1983) 35:816–26.
29 Black DW, Noyes R, Goldstein 38 Zohar J, Insel TR, Obsessive-
RB, Blum N, A family study of compulsive disorder: psychobio-
obsessive-compulsive disorder, logical approaches to diagnosis,
Arch Gen Psychiatry (1992) 49: treatment and pathophysiology,
362–8. Biol Psychiatry (1987) 2:667–87.
39 Goodman WK, Price LH, Delgado disorder, Arch Gen Psychiatry

PL et al, Specificity of serotonin (1992) 49:29–36.
reuptake inhibitors in the treat- 47 Leckman JF, Goodman WK,
ment of obsessive-compulsive North WG et al, The role of central
disorder, Arch Gen Psychiatry oxytocin in obsessive compulsive
(1990) 47:577–85. disorder and related normal
40 Hanna GL, McCracken JT, behavior, Psychoneuroendo-
Cantwell DP, Prolactin in child- crinology (1994) 19:723–49.
hood obsessive-compulsive dis- 48 McDougle CJ, Epperson CN,
order: clinical correlates and Price LH, Gelernter J, Evidence
response to clomipramine, J Am for linkage disequilibrium
Acad Child Adolesc Psych (1991) between serotonin transporter
30:173–8. protein gene (SLC6A4) and
41 McDougle CJ, Goodman WK, obsessive compulsive disorder,
Leckman JF, Barr LC, Heninger Molec Psych (1998) 3:270–3.
GR, Price LH, The efficacy of flu- 49 Billett EA, Richter MA, King N,
voxamine in obsessive compul- Heils A, Lesch KP, Kennedy JL,
sive disorder: effects of comorbid Obsessive compulsive disorder,
chronic tic disorder, J Clin Psy- response to serotonin reuptake
chopharmacol (1993) 13:354–8. inhibitors and the serotonin trans-
42 McDougle CJ, Goodman WK, porter gene. Molec Psych (1997)
Leckman JF, Lee NC, Heninger 2:403–6.
GR, Price LH, Haloperidol addi- 50 Altemus M, Murphy DL, Green-
tion in fluvoxamine-refractory berg B, Lesch KP, Intact coding
obsessive compulsive disorder: a region of the serotonin transporter
double blind placebo-controlled gene in obsessive-compulsive
study in patients with and without disorder, Am J Med Genet (Neu-
tics, Arch Gen Psychiatry (1994) ropsych Genet) (1996) 67:
51:302–8. 409–11.
43 Altemus M, Pigott T, Kalogeras KT 51 Enoch MA, Kaye WH, Rotondo A,
et al, Abnormalities in the regula- Greenberg BD, Murphy DL, Gold-
tion of vasopressin and corti- man D, 5-HT2A promoter poly-
cotropin releasing factor secretion morphism – 1438G/A, anorexia
in obsessive-compulsive disorder, nervosa, and obsessive-
Arch Gen Psychiatry (1992) 49: compulsive disorder, Lancet
9–20. (1998) 351:1785–6.
44 De Boer JA, Westenberg HGM, 52 Nicolini H, Cruz C, Camarena B et
Oxytocin in obsessive compulsive al, DRD2, DRD3 and 5HT2A
disorder, Peptides (1992) 13: receptor gene polymorphisms in
1083–5. obsessive-compulsive disorder,
45 Leckman JF, Goodman WK, Molec Psych (1996) 1:461–5.
North WG et al, Elevated levels of 53 Cruz C, Camarena B, King N et
CSF oxytocin in obsessive com- al, Increased prevalence of the
pulsive disorder: comparison with seven-repeat variant of the
Tourette’s syndrome and healthy dopamine D4 receptor gene in
controls, Arch Gen Psychiatry patients with obsessive-
(1994) 51:782–92. compulsive disorder with tics,
46 Swedo SE, Leonard HL, Kruesi MJ Neurosci Lett (1997) 231:1–4.
et al, Cerebrospinal fluid neuro- 54 Di Bella D, Catalano M, Cichon S,
chemistry in children and adoles- Nothen MM, Association study of
cents with obsessive-compulsive a null mutation in the dopamine
D4 receptor gene in Italian 59 Mundo E, Richter MA, Hood K,

patients with obsessive- Sam F, Macciardi F, Kennedy JL,
compulsive disorder, bipolar The TDT/sib-TDT procedure
mood disorder and schizophre- applied to the study of the
nia, Psychiatr Genet (1996) 6: 2HT1D␤ receptor gene and
119–21. obsessive-compulsive disorder,
55 Karayiorgou M, Altemus M, Galke Am J Hum Genet (1999)
BL et al, Genotype determining 65(suppl.):A437 [abstract].
low catechol-O-methyltransferase 60 Stern L, Zohar J, Cohen R, Sas-
activity as a risk factor for son Y, Treatment of severe, drug
obsessive-compulsive disorder, resistant obsessive compulsive
Proc Nat Acad Sci USA (1997) disorder with the 5HT1D agonist
94:4572–5. sumatriptan, Eur Neuropsycho-
56 Alsobrook JP, Zohar AH, LeBoyer pharmacol (1998) 8:325–8.
M, Chabane N, Ebstein RP, Pauls 61 Spielman RS, Ewens WJ, A sib-
DL, Association between the ship test for linkage in the pres-
COMT locus and obsessive com- ence of association: the sib
pulsive disorder in females but transmission/disequilibrium test,
not males, Am J Med Genet (Neu- Am J Hum Genet (1998) 62:
ropsych Genet) (2000) in press. 450–8.
57 Novelli E, Nobile M, Diaferia G, 62 Lappalainen J, Dean M, Charbon-
Sciuto G, Catalano M, A molecu- neau L, Virkkunen M, Linnoila M,
lar investigation suggests no rela- Goldman D, Mapping of the sero-
tionship between obsessive- tonin 5-HY1D␤ autoreceptor gene
compulsive disorder and the on chromosome 6 and direct
dopamine D2 receptor, Neu- analysis for sequence variants,
ropsychobiology (1994) 29:61–3. Am J Hum Genet (1995)
58 Catalano M, Sciuto G, Di Bella D, 60:157–61.
Novelli E, Nobile M, Bellodi L, 63 Kidd KK, New genetic strategies
Lack of association between for studying psychiatric disorders.
obsessive-compulsive disorder In Genetic Aspects of Human
and the dopamine D3 receptor Behavior (Eds. Sakai T, Tsuboi T.)
gene: some preliminary consider- Igaku-Shoin Ltd: (Tokyo, 1985)
ations, Am J Med Genet (Neu- 325–46.
ropsych Genet) (1994) 54:253–5.
7
The neuroanatomy of OCD
James V Lucey
Obsessive compulsive disorder (OCD) has been classified as an anxiety

disorder within a rubric that also includes panic disorder (with or without
agoraphobia), generalized anxiety disorder (GAD), and post-traumatic
stress disorder (PTSD).1 However, OCD is increasingly recognized as a
brain disorder.2 This neuropsychiatric view of OCD is supported first by
the clinical association of OCD with diseases of the cerebral cortex and
the neostriatum, and second by functional imaging data reporting associ-
ations between OCD and activity in corticostriatal brain regions.
Neuropsychiatric features of OCD
Since its clinical description by Westphal in 1878,3 OCD has been asso-
ciated with movement disorders and neurological conditions. Modern
biological psychiatrists have reiterated these observations.4 Although
most OCD patients do not have gross cerebral lesions,5 discrete lesions
of the basal ganglia are associated with obsessive compulsive phenom-
ena.6 Obsessive compulsive disorder may develop following head injury,7
birth injury,8 or temporal lobe epilepsy.5 Furthermore, neurosurgical treat-
ments such as subcaudate tractotomy (in which cortical connections to
deep striatal structures are severed) are still effective in rare resistant
cases.9
More subtle neurological dysfunction (indicated by abnormalities of
fine motor coordination, involuntary movements, sensory dysfunction and
visuospatial errors) may be seen in OCD.10 Furthermore OCD patients
with high scores on a soft-signs neurological investigation are found to
have increased ventricular volumes on computerized tomography.11
Movement disorders with striatal involvement are associated with
increased incidence of OCD symptoms.12,13 Symptoms of OCD are more
common in postencephalitic Parkinson’s disease and Sydenham’s
chorea,12,14 and the presence of chorea implies basal ganglia involvement.
77
Gilles de la Tourette’s syndrome (GTS) is a chronic neuropsychiatric

disorder of childhood onset characterized by motor and phonic tics that
wax and wane in intensity. Nearly 70% of GTS patients have obsessive
compulsive symptoms.15,16 Obsessive compulsive disorder is prevalent in
up to 23% of first-degree relatives of GTS probands.15 In some OCD sam-
ples 6% meet criteria for GTS.16 Tics are repetitive, involuntary motor
actions prevalent in up to 38% of OCD patients.16 In a study of 50 Irish
OCD outpatients, GTS was rare (2%), but tics were common.17
Functional anatomy of OCD

Just how the mammalian brain mediates obsession, compulsion and
fear-related behaviour is far from clear. The data suggest that both nor-
mal and abnormal fear-related behaviours involve deep brain structures
as well as the cerebral cortex.18 Among the relevant deep structures
involved are the components of the limbic system, including the hypo-
thalamus, septum, hippocampus, amygdala and the cingulum; other
bodies such as the thalamus, locus coeruleus, median raphe nuclei and
the dentate/interposital nuclei of the cerebellum.
In OCD, according to the hypothesis of Gray,19 the septo-hippocampal
system (SHS) becomes oversensitive and labels too many incoming stim-
uli as important. This leads to persistent searching for those stimuli, with
resultant checking and ritualizing. The role of the amygdala in the media-
tion of emotional behaviour has been recognized for over half a century.20
It is now known to have a central part in the mediation of anxiety and con-
ditioned fear.21 The amygdala in humans has been shown to be involved
in varied aspects of fear conditioning,22 emotional memory,23 and recog-
nition of vocal intonations or facial expressions.24 Indeed, different types
of conditioned behaviour may be mediated by separate nuclei within the
amygdala.25
Bilateral hippocampal lesions in rats produce repetitive behaviours that
invariably include excessiveness, retarded extinction of learned behav-
iour, and increased avoidance.26 There have been numerous cases of
OCD symptoms arising following the development of diabetes insipidus
or encephalitis lethargica.12 According to Pitman, the similarities between
symptoms and behaviours in OCD and neurobehavioural findings in ani-
mals with limbic structure damage ‘are too close to be ignored by any
theory of OCD causation’.26
There is also evidence to suggest that the cingulum (cingulate lobe),
which is a medial area of the brain just dorsal to the corpus callosum,
might be involved in OCD. Grey-Walter proposed that overactivity of the
cingulate region led to compulsive behaviour.27 Some of the most con-
vincing evidence of the role of the cingulum in OCD comes from the liter-
ature on psychosurgery.2 Tippin and Henn reported five severely
Neuroanatomy 79
obsessional patients who improved (with full remission in one) after modi-
fied leucotomy in which the medial 2–3 cm of white matter coming
through the anterior cingulate gyrus was severed.28 The procedure is
thought to be effective by disrupting the thalamofrontal tract.
The neostriatal hypothesis of OCD
The orbitofrontal cortex, ventral striatum, globus pallidus and thalamus

are anatomically connected in a loop.29 These regions are thought to
comprise a neural network involved in switching patterns of behaviour.30
In addition to their role in motor control and movement disorder, the
structures of the neostriatum contribute to skeletomotor, oculomotor, cog-
nitive and limbic processes.29,31 The neostriatal hypothesis of OCD states
that (orbitofrontal) corticostriatal overactivity underlies the disorder.32
These regions are most consistently reported as showing altered activity
in resting state functional imagining of OCD.33
Imaging of OCD
In a study regarded as a landmark in the understanding of anxiety disor-

ders, Baxter et al compared regional cerebral metabolic rate (rCMRglucose)
measured using [18F]fluorodeoxyglucose (18-FDG) positron emission
tomography (PET) in 14 OCD patients and depressed and healthy con-
trols.34 This revealed a significant increase in absolute levels of
rCMRglucose in the OCD left orbitofrontal gyrus and bilateral caudate
nucleus.34 This same group replicated their findings in 10 OCD patients
without substantial depressive comorbidity, showing elevated rCMRglucose
in the orbital gyri and the caudate bilaterally.35 The orbitofrontal regional
rCMRglucose was elevated in these patients, in marked contrast to the
reduced rCMRglucose seen in the prefrontal cortex of patients with unipolar
depression.34 Similar results were reported in a study of 8 non-depressed
OCD patients compared with 30 healthy volunteers, in which 18-FDG PET
demonstrated increased normalized rCMRglucose in the right and left
orbitofrontal cortex. No caudate differences were seen in this study.36
Increased rCMRglucose in the left orbitofrontal, right sensorimotor and bilat-
eral prefrontal and anterior cingulate cortex in OCD was again found on
PET in 18 adults with childhood-onset OCD compared with matched
adult controls. Once again, both absolute and normalized caudate differ-
ences failed to reach significance.14
Three bilateral cortical regions were hypermetabolic in a PET study
using oxygen 15 in OCD patients with a syndrome of obsessional slow-
ness: the orbitofrontal cortex, the premotor cortex and the midfrontal cor-
tex.37 This study also examined striatal dopaminergic function using
[18F]6-fluorodopa on PET and found normal uptake in the caudate, puta-

men and medial frontal cortex.37
Only one study has found a reduction in frontal cortical rCMRglucose in
OCD. In this study by Martinot et al the control group had substantially
higher rCMRglucose values than did others.38 The patients were older and
had a longer duration of illness (mean of 18 years). Baxter et al acknowl-
edged that his subjects’ elevated orbitofrontal rCMRglucose could be
related to high levels of anxiety.34
In PET studies after treatment with the serotonin reuptake inhibitor (SRI)
clomipramine hydrochloride, rCMRglucose was significantly reduced in the
orbital frontal cortex and left caudate nucleus. Significant reductions
were confined to the left caudate nucleus.39 Likewise, Swedo et al found
a reduction in rCMRglucose in orbitofrontal cortex bilaterally in 13 OCD
patients after 1 year of successful SRI treatment.40 In one European study
significant improvement on SRI treatment was also associated with
decreased metabolism in the cingulate cortex.41
After treatment rCMRglucose in the head of the right caudate nucleus was
significantly reduced in responders, regardless of whether pharmacologi-
cal or psychological treatment was used.42 Changes in OCD symptoms
correlated significantly with reductions in caudate rCMRglucose in med-
icated subjects.42 In a further study from the same centre, Schwartz et al
replicated and extended these findings for a group of OCD patients
(n ⫽ 18) treated exclusively with psychological methods.43 The behaviour
treatment involved exposure, response prevention and cognitive restruc-
turing. Responders had significant bilateral decreases in rCMRglucose,
which were greater than those of non-responders. The authors con-
cluded that a corticostriato–thalamic brain system is implicated in the
mediation of OCD symptoms.43 It seems that alteration of striatal
rCMRglucose is intimately associated with symptomatic recovery in OCD
regardless of whether the treatment is pharmacologically or psychologi-
cally mediated.
Structural imaging
It seems improbable that OCD functional imaging differences could exist

in the absence of some structural differences.2 Some studies using com-
puterized tomography and magnetic resonance imaging (MRI) found
OCD caudate nuclear volume was reduced.44,45 Normal caudate volumet-
ric studies are also reported.11,46,47 One structural MRI study of OCD
patients, in comparison with healthy controls, found significantly less total
white matter and significantly greater total cortex and opercular volumes,
which correlated significantly with OCD syndrome severity.48
Neuroanatomy 81
Studies during behavioural challenge

To focus on the neural mechanisms of the disease process itself, a num-
ber of nuclear medicine researchers use challenge paradigms, capitaliz-
ing on the experience of OCD behaviour therapists and the adaptability
of PET imaging. By exposing OCD patients to increasing amounts of anx-
iogenic stimulus, these researchers attempt to visualize the brain basis of
obsessions and rituals. Zohar et al administered behavioural challenges
to 10 OCD patients while measuring rCBF with xenon 133 inhalation on
single photon emission tomography (SPET).49 Each patient was studied
under three conditions: relaxation, imaginal flooding (in fantasy) and in
vivo (actual) exposure to the anxiogenic stimulus. Subjective anxiety,
obsessive compulsive ratings and autonomic measures (heart rate, blood
pressure) increased significantly, but respiratory rate and PCO2 did not
change across the three conditions. Temporal cortical rCBF increased
slightly during imaginal flooding, but rCBF decreased markedly in other
cortical regions during in vivo exposure, when anxiety was highest by
subjective and peripheral autonomic measures. As Gur et al had earlier
proposed,50 intense anxiety was associated with decreased rather than
increased cortical perfusion, and related states of anxiety (e.g. anticipa-
tory and obsessional anxiety) appeared to be associated with opposite
effects on rCBF.
A later challenge study attempted to delineate the mediating neuro-
anatomy of OCD using the short half-life tracer labelled carbon dioxide
([15O]CO2), for repeated PET determinations of rCBF in 8 OCD patients
during resting and provoked (symptomatic) states.51 There was a signifi-
cant increase in relative rCBF during symptomatic states in the right cau-
date nucleus, the left anterior cingulate cortex, and the orbitofrontal
cortex bilaterally. Increases in the thalamus approached but did not
reach statistical significance. Using a similar paradigm, McGuire et al
examined 4 OCD patients using 15O-labelled H2O PET; each patient was
scanned 12 times during the same session.30 Each scan was paired with
brief exposure to a hierarchy of contaminants that elicited increasingly
intense urges to ritualize. There was a significant relationship between
symptom intensity and neural activity (rCBF) in the right inferior frontal
gyrus, caudate nucleus, putamen, globus pallidus and thalamus, and
also the left hippocampus and posterior cingulate gyrus. Negative corre-
lations were also seen in the right superior prefrontal cortex and tem-
poroparietal cortex. These authors hypothesized that in OCD rCBF
increases occurred in the orbitofrontal cortex, the neostriatum, the globus
pallidus and the thalamus, in response to the urge to perform compulsive
rituals. Hippocampal and cingulate changes appeared to relate to the
associated anxiety.30
Functional MRI (fMRI) images in controlled and provoked (sympto-
matic) conditions were studied in 10 OCD patients and 5 healthy
controls. No healthy subject revealed any activation. In contrast, sympto-

matic OCD patients activated areas consistent with previous PET and
SPET imaging studies: these included the orbitofrontal, lateral frontal,
anterior temporal, anterior cingulate and insular cortex, as well as the
caudate and lenticular nuclei and the amygdala.52
SPET imaging
Other OCD functional imaging research groups have examined rCBF as

uptake of technetium 99m hexamethyl propylenamine oxime (99mTc-
HMPAO) on single photon emission tomography as an index of regional
neural activity. Machlin et al used this method to estimate rCBF in 10
OCD patients and 8 controls using a single rotating SPET system with a
16 mm resolution; they found increased medial frontal rCBF in OCD.53
There was no increase in orbitofrontal rCBF and no correlation with symp-
toms. They limited their comments to cortical regions.53 Six of these
patients were seen following treatment with an SRI (fluoxetine 20 mg per
day) and their symptom ratings were significantly reduced. Subsequent
SPET scanning showed that OCD medial frontal and whole brain blood
flow were significantly reduced following treatment.54
Basal ganglia hypoperfusion was first seen on 99mTc-HMPAO SPET in a
preliminary study in Canada.55 In this study 11 OCD patients were evalu-
ated for distribution of radioactive tracer: 8 demonstrated asymmetric
perfusion, 6 of whom showed left-sided hypoperfusion of the basal gan-
glia. The study was limited since the analysis was qualitative and uncon-
trolled. A more rigorous analysis of 99mTc-HMPAO SPET uptake was
provided by Edmonstone et al.56 This study used a multidetector brain-
dedicated SPET system with a resolution of 7.5 mm to compare OCD
patients with healthy and depressed controls. Significant bilateral
decreases in uptake were confined to the striatum (caudate and puta-
men) in the OCD group, despite an apparently paradoxical positive cor-
relation between blood flow and anxiety.56
Rubin et al examined 133Xe rCBF and regional cerebral 99mTc-HMPAO
uptake on SPET in 10 adult men with OCD and 10 matched controls. With
the 133Xe method they found no rCBF differences, although there was a sig-
nificant positive relationship between measures of illness severity and 133Xe
CBF.57 Compared with healthy controls OCD patients had significantly ele-
vated 99mTc-HMPAO uptake (rCBF) bilaterally in the orbitofrontal and the
dorsal parietal cortex as well as the left posterofrontal cortex. In the OCD
patients 99mTc-HMPAO uptake was significantly reduced bilaterally in the
caudate nucleus but not in the putamen or thalamus.57 Further support for
the involvement of the orbitofrontal cortex and the caudate nucleus in OCD
was provided by Rubin et al when they reported using regional 133Xe CBF
and 99mTc-HMPAO SPET to examine rCBF in OCD before and during treat-
Neuroanatomy 83
ment.58 Despite clomipramine treatment, significant bilateral reductions in

OCD caudate 99mTc-HMPAO uptake remained.58
The SPET method was used to examine 99mTc-HMPAO uptake or
regional cerebral blood flow in seven brain regions in 30 OCD patients
compared with 30 healthy controls.17 The rCBF was lower in the OCD
group in the right superior frontal cortex, right inferior frontal cortex, right
caudate and right thalamus. It was also lower in the left superior frontal,
left lateral temporal and left parietal cortex. In addition there were signifi-
cant differences in the right medial temporal cortex, left lateral temporal
cortex and left parietal cortex. Illness severity, compulsivity and obses-
sionality all correlated with regional blood flow.
The most prominent and widespread correlation was between the
Yale–Brown Obsessive Compulsive Scale (Y–BOCS, see Appendix 1 p. 183)
compulsion scores and rCBF. Compulsions correlated with rCBF to the
right superior frontal cortex, right inferior frontal cortex, left inferior frontal
cortex, left lateral temporal cortex, right medial temporal cortex, right and
left parietal cortex and medial frontal (cingulate) cortex, and right and left
thalami. Thus SPET data provide regional support for the neostriatal
hypothesis.59 However, these data did not support the view that overactivity
in this loop is necessarily involved. Indeed, consistent with other 99mTc-
HMPAO SPET studies, reduced uptake was found in the OCD striatum. In
OCD, striatal uptake of 99mTc-HMPAO is consistently reduced on
SPET.17,55–58 Moreover, the evidence did not conclusively point to a selec-
tive OCD pathology within the orbitofrontal corticostriate loop. Involvement
of the medial frontal (cingulate region) was also evident. Multiple regres-
sion analysis confirmed that changes in right parietal rCBF had prominent
correlation with obsessive-compulsivity.17 This is consistent with previous
SPET and PET studies showing reduced OCD right parietal blood flow dur-
ing exposure to ritual-evoking stimuli.30,49 The evidence suggests that a role
for the cingulate and the parietal lobe should not be omitted from neu-
roanatomical models of OCD. Thus other regions connected by the limbic
loop are also involved in experience intrinsic to OCD.60
Neuroanatomy: an overview
Patients with OCD have been studied using a variety of functional imag-
ing technologies such as positron emission tomography, single photon
emission tomography and functional magnetic resonance imaging. They
have been examined at rest, in comparison with depressed and anxious
and healthy controls, on exposure to anxiogenic stimuli, and after phar-
macological or psychological treatment. These patients repeatedly dis-
play brain differences involving the orbitofrontal cortex, cingulate gyrus,
parietal lobe, caudate nucleus and thalamus. Such findings are among
the most consistent imaging data in psychological medicine.
References
1 World Health Organization, The B et al, Neurological soft signs in
ICD-10 Classification of Mental obsessive compulsive disorder,
and Behavioural Disorders: Clini- Arch Gen Psychiatry (1991)
cal Description and Diagnostic 48:278–9.
Guidelines (WHO: Geneva, 1992), 11 Stein DJ, Hollander E, Chan S et
142–5. al, Computed tomography and
2 McGuire PK, The brain in soft signs in obsessive compul-
obsessive-compulsive disorder, sive disorder, (1993) Psychiatr
Neurol Neurosurg Psych (1995) Res Neuroimaging (1993) 50:
59:457–9. 143–50.
3 Westphal C, Dwangforstellungen, 12 Von Economo C (Newman KO
Arch Psych Nervenkr (1878) 8: trans.), Encephalitis Lethargica:
734–50. Its Sequelae and Treatment
(Oxford University Press: London,
4 Rapoport JL, Obsessive-
1932).
compulsive disorder and basal
ganglia dysfunction, Psychol Med 13 Swedo SE, Leonard HL, Child-
(1990) 20:465–9. hood movement disorders and
obsessive compulsive disorder, J
5 Kettl PA, Marks IM, Neurological Clin Psychiatry (1994) 55(3):
factors in obsessive compulsive S32–7.
disorder; two case reports and a
review of the disorder, Br J Psy- 14 Swedo SE, Shapiro MB, Grady CI
chiatry (1986) 149:315–19. et al, Cerebral glucose metabo-
lism in childhood onset obsessive
6 Tonkonogy J, Barreira P, compulsive disorder, Arch Gen
Obsessive-compulsive disorder Psychiatry (1989) 46:518–23.
and caudate-frontal lesion, Neu-
ropsych Neuropsychol Behav 15 Pauls DL, Towbin KE, Leckman
Neurol (1989) 2:203–9. JF et al, Gilles de la Tourettes
syndrome and obsessive compul-
7 McKeon J, McGuffin P, Robinson sive disorder, Arch Gen Psychia-
R, Obsessive compulsive neuro- try (1986) 43:1180–2.
sis following head injury – a report
of four cases, Br J Psychiatry 16 Pitman RK, Green RC, Jenike MA,
Mesulam MM, Clinical compari-
(1984) 144:190–2.
son to Tourette’s disorder with
8 Capstick N, Seldrup J, Obses- obsessive-compulsive disorder,
sional states: a study of the rela- Am J Psychiatry (1987) 144(9):
tionship between abnormalities 1166–71.
occurring at birth and the subse-
17 Lucey JV, Costa DC, Blanes T et
quent development of obses-
al, Regional cerebral blood flow in
sional symptoms, Acta Psych obsessive compulsive disordered
Scand (1977) 56:427–31. patients at rest: differential corre-
9 Chiocca EA, Martuza RL, Neuro- lates with obsessive-compulsive
surgical treatment of the and anxious-avoidant dimen-
obsessive-compulsive disorder. sions, Br J Psychiatry (1995)
In: Jenike MA, Baer L, Minichiello 167:629–34.
WE et al, eds, Obsessive-compul- 18 Marks IM, Phobic and obsessive
sive Disorders: Theory and Man- compulsive phenomena: classifi-
agement (Mosby Year Book: St cation, prevalence and relation-
Louis, 1990) 283–94. ship to other problems. In: Fears,
10 Hollander E, Schiffman E, Cohen Phobias and Rituals: Panic Anxi-
Neuroanatomy 85
ety and their Disorders (OUP: 29 Alexander GE, DeLong M, Strick

Oxford, 1987) 281–90. P, Parallel organisation of func-
19 Gray JA, The Neuropsychology of tionally segregated circuits linking
Anxiety: An Enquiry into the Func- the basal ganglia and cortex, Ann
tion of the Septohippocampal Rev Neurosci (1986) 9:357–81.
System (Oxford University Press: 30 McGuire PK, Bench CJ, Frith CD,
New York, 1982). Marks IM, Frackowiak RSJ, Dolan
20 Kluver H, Bucy PC, Preliminary RJ, Functional anatomy of obses-
analysis of the temporal lobes in sive compulsive phenomena, Br J
monkeys, Arch Neurol Psych Psychiatry (1994) 164:459–68.
(1939) 42:979–1000. 31 Alexander GE, Crutcher MD,
DeLong MR, Basal ganglia–thala-
21 Davis M, The role of the amyg-
mocortical circuits: parallel sub-
dala in fear and anxiety, Ann Rev
strates for motor, oculomotor,
Neurosci (1992) 15:353–75.
prefrontal and limbic functions. In:
22 Bechara A, Tranel D, Damasio H, Uylings HBM, Van Eden CG,
Adolphs R, Rockland C, Damasio DeBruin JPC, Corner MA, Feen-
AR, Double dissociation of the stra MGP, eds, Progress in Brain
conditioning and declarative Research (Elsevier: Amsterdam,
knowledge relative to the amyg- 1990): 119–46.
dala and hippocampus in humans.
32 Cummings JL, Frontal subcortical
Science (1995) 269:1115–18.
circuits and human behaviour.
23 Cahill L, Babinsky R, Markowitsch Review, Arch Neurol (1993)
H, McGaugh JL, The amygdala 50(8):873–8.
and emotional memory, Nature 33 Schwartz JM, Neuroanatomical
(1995) 377:295–6. aspects of cognitive behavioural
24 Adolphs R, Tranel D, Damasio H, therapy responses in obsessive
Damasio A, Impaired recognition compulsive disorder, Br J Psychi-
of emotion in facial expression fol- atry (1998) suppl. 35:38–44.
lowing bilateral damage to the 34 Baxter LR, Phelps ME, Mazziotta
human amygdala, Nature (1994) JC, Guze BH, Schwartz JM, Selin
372:669–72. CE, Local cerebral glucose meta-
25 Killcross S, Robbins TW, Everitt bolic rates in obsessive-
BJ, Differential types of fear- compulsive disorder: a
conditioned behaviour mediated comparison with unipolar depres-
by separate nuclei within the sion and normal controls, Arch
amygdala, Nature (1997) 388: Gen Psychiatry (1987) 44:211–18.
377–80. 35 Baxter LR, Schwartz JM, Mazziota
26 Pitman RK, Neurological aetiology JC et al, Cerebral glucose meta-
of obsessive compulsive disor- bolic rates in non-depressed
ders? Am J Psychiatry (1982) obsessive compulsive disorder,
139:139–40. Am J Psychiatry (1988) 145:
27 Grey-Walter WG, Viewpoints of 1560–3.
mental illness: neurophysiological 36 Nordahl TE, Benkelfat C, Semple
aspects, Semin Psychiatry (1977) WE, Gross M, King AC, Cohen
14:211–31. RM, Cerebral glucose metabolic
28 Tippin J, Henn FA, Modified rates in obsessive compulsive
leukotomy in the treatment of disorder, Neuropsychopharma-
intractable obsessional neurosis, cology (1989) 2:23–8.
Am J Psychiatry (1982) 139: 37 Sawle G, Hymas N, Lees A,
1601–3. Frakowiak R, Obsessional slow-
ness: functional studies with al, Reduced caudate nucleus vol-

positron emission tomography, ume in obsessive-compulsive dis-
Brain (1991) 114:2191–202. order, Arch Gen Psychiatry
38 Martinot JL, Allilaire JF, Mazoyer (1995) 52:393–8.
BM et al, Obsessive-compulsive 46 Garber HJ, Ananth JV, Chiu LC,
disorder: a clinical, neuropsycho- Griswold VJ, Oldendorf WH,
logical and positron emission Nuclear magnetic resonance
study, Acta Psych Scand (1990) imaging in obsessive compulsive
82:233–42. disorder, Am J Psychiatry (1989)
39 Benkelfat C, Nordahl TE, Semple 146:1001–5.
WE, Local cerebral glucose meta- 47 Aylward EH, Harris GJ, Hoehn-
bolic rates in obsessive- Saric R, Barta PE, Machlin SR,
compulsive disorder: patients Pearlson GD, Normal caudate
treated with clomipramine, Arch nucleus in obsessive-compulsive
Gen Psychiatry (1990) 47:840–8. disorder assessed by quantitative
neuroimaging, Arch Gen Psychia-
40 Swedo SE, Pietrini P, Leonard HL
try (1996) 53:577–84.
et al, Cerebral glucose metabo-
lism in childhood onset obsessive 48 Jenike MA, Breiter HC, Baer L et
compulsive disorder: revisualiza- al, Cerebral structural abnormali-
tion after pharmacotherapy, Arch ties in obsessive compulsive
Gen Psychiatry (1992) 49:690–4. disorder: a quantitative morpho-
metric magnetic resonance imag-
41 Perani D, Colombo C, Bressi S et ing study, Arch Gen Psychiatry
al, [18F]FDG PET study in (1996) 53:625–32.
obsessive-compulsive disorder. A
clinical/metabolic correlation 49 Zohar J, Insel TR, Berman KF,
study after treatment, Br J Psychi- Foa EB, Hill JL, Weinberger DR,
atry (1995) 166(2):244–50. Anxiety and cerebral blood flow
during behavioural challenge.
42 Baxter LR, Schwartz JM, Dissociation of central from
Bergman KS et al, Caudate glu- peripheral and subjective mea-
cose metabolic rate changes with sures, Arch Gen Psychiatry
both drug and behaviour therapy (1989) 46:505–10.
for obsessive-compulsive disor-
50 Gur RC, Gur RE, Resnick SM,
der. Arch Gen Psychiatry (1992)
Skolnick BE, Alavi A, Reivch M,
49:681–9.
The effect of anxiety on cortical
43 Schwartz JM, Stoessel PW, Bax- cerebral blood flow and metabo-
ter LR, Martin KM, Phelps ME, lism, J Cerebr Blood Flow Metab
Systematic changes in cerebral (1987) 7:173–7.
glucose metabolic rate after suc-
51 Rauch SL, Jenike MA, Alpert NM et
cessful behaviour modification al, Regional cerebral blood flow
treatment of obsessive- measured during symptom provo-
compulsive disorder, Arch Gen cation in obsessive-compulsive
Psychiatry (1996) 53:109–13. disorder using oxygen 15-labeled
44 Luxenberg JS, Swedo SE, Fla- carbon dioxide and positron emis-
ment MF, Friedland RP, Rapoport sion tomography, Arch Gen Psy-
J, Rapoport SI, Neuroanatomical chiatry (1994) 51(1):62–70.
abnormalities in obsessive- 52 Breiter HC, Rauch SL, Kwong KK
compulsive disorder detected et al, Functional magnetic reso-
with quantitative x-ray computed nance imaging of symptom
tomography, Am J Psychiatry provocation in obsessive compul-
(1988) 145:1089–93. sive disorder, Arch Gen Psychia-
45 Robinson D, Wu H, Munne RA et try (1996) 53:595–606.
Neuroanatomy 87
53 Machlin SR, Harris GJ, Pearlson 57 Rubin R, Villanueva-Meyer J,

GD et al, Elevated medial frontal Ananth J, Trajmar PG, Mena I,
cerebral blood flow in obsessive Regional Xenon-133 cerebral
compulsive patients: a SPET blood flow and cerebral tech-
study, Am J Psychiatry (1991) netium 99m-HMPAO uptake in
148:1240–2. un-medicated patients with
obsessive-compulsive disorder
54 Hoehn-Saric R, Pearlson GD, Har- and matched normal controls,
ris GJ, Machlin SR, Camargo EE, Arch Gen Psychiatry (1992) 49:
Effects of fluoxetine on regional 695–702.
cerebral blood flow in obsessive-
compulsive patients. Am J Psy- 58 Rubin R, Ananth J, Villanueva-
chiatry (1991) 148:1242–5. Meyer J, Trajmar PG, Mena I,
Regional 133xenon cerebral
55 Adams BL, Warneke LB, McEwan blood flow and cerebral 99mTc-
AJ, Fraser BA, Single photon HMPAO uptake in patients with
emission computerised tomogra- obsessive-compulsive disorder
phy in obsessive compulsive dis- before and during treatment, Biol
order: a preliminary study, J Psychiatry (1995) 38:429–37.
Psych Neurosci (1993) 18(3): 59 Lucey JV, Costa DC, Busatto GF
109–12. et al, Caudate regional cerebral
56 Edmonstone Y, Austin MP, Pren- blood flow in obsessive compul-
tice N et al, Uptake of 99m-Tc- sive disorder and panic disorder,
exametazime shown by photon Psychiatr Res Neuroimaging
emission computerised tomogra- (1997) 74:25–33.
phy in obsessive compulsive dis- 60 Heimer L, The olfactory cortex
order compared with major and the ventral striatum. In: Liv-
depression and normal controls, ingston KE, Hornykiewesz O, eds,
Acta Psych Scand (1994) 90: Limbic Mechanisms (Plenum:
298–303. New York, 1978) 95–7.
8
Integrated pathophysiology
Donatella Marazziti
Serotonin and OCD
For more than a decade, the serotonin (5-HT) hypothesis of obsessive

compulsive disorder (OCD) constituted a frame of reference for
approaching the biology and pathophysiology of this disease. The first
observations were those related to the effectiveness of clomipramine (a
tricyclic antidepressant which preferentially blocks 5-HT reuptake), com-
pared with other tricyclics or placebo, subsequently confirmed by the
superiority of selective serotonin reuptake inhibitors (SSRIs) such as flu-
oxetine, fluvoxamine, paroxetine, sertraline and citalopram.1–4 Moreover,
indications of 5-HT involvement came also from cerebrospinal fluid (CSF)
studies of 5-hydroxyindoleacetic acid (5-HIAA) in OCD, which have
shown that a positive response to clomipramine was associated with high
CSF levels of 5-HIAA,5,6 while low levels correlated negatively with
response to clomipramine and positively with obsessive compulsive (OC)
symptom severity.7 Other supporting evidence derived from the exacer-
bations of OC symptoms with 5-HT agonists led to the hypothesis of
hypersensitivity of postsynaptic 5-HT receptors in OCD, a hypothesis that
is still considered valid.8–10
Platelet studies
The main target of clomipramine and SSRIs, the 5-HT transporter, has
been investigated in OCD for its presence in blood platelets: in fact, the
active uptake for 5-HT in these cells is similar to that present in the brain,
as demonstrated by the cloning of the two structures.11,12 For some years,
[3H]-imipramine (3H-IMI), has been mainly used to label it.13 However,
pharmacological studies in this field have shown heterogeneity of IMI
binding sites when desipramine is used to define ‘specific’ binding.14
Desipramine-defined IMI binding appears to be constituted by two sub-
populations: only that being a protein, 5-HT-sensitive and sodium-
dependent would be present in serotonergic neurons and related to the
89
5-HT transporter.15 Insel et al found no difference in either 5-HT uptake or

3
H-IMI binding between healthy controls and OC patients,5 and Weizman
et al and Marazziti et al observed normal 5-HT uptake coupled with a
reduced number of 3H-IMI binding sites.16,17 Black et al replicated Insel
et al’s finding of no change in 3H-IMI binding, except for a decrease in
such binding sites in clomipramine-treated patients,18 while other studies
have shown a decreased number of 3H-IMI binding sites and a
decreased affinity for 5-HT uptake,19 as well as an increased velocity of
5-HT uptake, with no change in 3H-IMI binding.20 Subsequently, it has
been demonstrated that the more selective ligand [3H]-paroxetine (3H-
Par) binds to a single site, probably corresponding to the neuronal trans-
porter,21,22 and a significant decrease in the number of 3H-Par binding
sites, as compared with healthy controls, has been more recently
reported by two groups.23,24 Such a decrease appears to constitute a
state-dependent marker, as it is reversed by successful treatment with
different SSRIs.25 In addition, this and other reports suggest that the
patients showing the most ‘severe’ serotonergic abnormalities are those
who respond better to the drugs and, therefore, link the serotonergic
alteration to a positive response to serotonergic drugs.25–27
Pharmacological responses
The identification of at least 17 subtypes of 5-HT receptor28 has led to the
question of which subtype or subsystem might be primarily implicated in
OCD. Besides the blockade of the 5-HT transporter, clomipramine
enhances the responsiveness of the postsynaptic 5-HT1A receptor and
provokes a desensitization of 5-HT2C receptors, while SSRIs cause a
decrease in somatodendritic and terminal autoreceptor responsiveness.29
The net increase in 5-HT release provoked by the two actions is particu-
larly evident in the orbitofrontal cortex, an area that appears primarily
implicated in OCD, after an 8-week time lag consistent with the delayed
response to these drugs typical of OCD patients and at variance with
depression. In addition, high doses of SSRIs are required to elicit this
effect, in agreement with the clinical observation that OCD patients need
higher doses than depressed patients. The effect of 5-HT in the
orbitofrontal cortex has been linked to 5-HT2-like receptors, since it is
reversed by prolonged administration of 5-HT2 antagonists. Clinical
observation supports the notion that drugs blocking the 5-HT transporter
display antiobsessional properties by increasing serotonergic transmis-
sion: both metergoline and ritanserin, non-selective 5-HT antagonists,
seem to provoke symptoms in drug-remitted patients.30,31 The role of
5-HT2-like receptors is supported by preliminary observations of the anti-
obsessional effect of psilocybin, a hallucinogen with 5-HT agonist proper-
ties,32 and by the clinical benefit in resistant OCD of atypical neuroleptics,
such as risperidone, with a 5-HT2/D2 profile.33
Integrated pathophysiology 91
Drug challenge tests

Another useful approach for exploring receptor subtypes is represented
by drug challenge tests. Although the related findings are questionable
because no sufficiently selective compound is currently available, never-
theless these tests provide dynamic studies of the receptors and raise
interesting suggestions. The most frequently employed challenge uses
m-chlorophenylpiperazine (m-CPP),8,9,34 a partial 5-HT agonist with 5-
HT1A, 5-HT1B/D, 5-HT2C, 5-HT2 receptor agonist and 5-HT2 receptor antago-
nist properties, which also inhibits 5-HT reuptake and displaces 3H-Par
binding to the 5-HT transporter, provoking exacerbation of OC symp-
toms. In contrast, 2-chloro-6(-1-piperazinyl)pyrazine (MK-212), a 5-HT1A
and 5-HT2C receptor agonist, provokes no behavioural effect in OCD.35
The main difference between m-CCP and MK-212 is represented by the
fact that the latter compound shows no affinity for 5-HT1B/D receptors. The
possible role of 5-HT1B/D receptors was investigated by means of suma-
triptan, an agonist at this level, but data are still meagre and controver-
sial: while some authors reported exacerbation of obsessive symptoms,36
others did not observe any change in 15 patients except a significant
increase in growth hormone response.37 Certainly, the matter needs to be
further investigated, perhaps with 5-HT1B/D receptor agonists with better
brain-penetrating properties than sumatriptan, which does not easily
pass the blood-brain barrier.
Receptor subtypes
The overall data suggest the involvement of the following 5-HT receptor
subtypes: 5-HT1A, 5-HT2A, 5-HT2C and 5-HT1B/D receptors. The 5-HT1A
receptor subtype does not appear to be altered in OCD patients, as
shown by the absence of effect after challenge with ipsapirone, a 5-HT1A
receptor agonist,38 and by the lack of clinical efficacy of buspirone,39 so
that the use of this drug in augmentation strategies is no longer recom-
mended. The question of the role of the 5-HT2A, 5-HT2C and 5-HT1B/D
receptors in OCD is still open and deserves further investigation. How-
ever, we cannot disregard the potential involvement of other receptor
subtypes: in particular, the 5-HT5A and 5-HT6 subtypes where
clomipramine seems to interact, and 5-HT1F where sumatriptan displays
agonistic activity to the same degree as that exerted at the level of 5-HT1D
receptors. With regard to other receptor subtypes, the status of 5-HT3
receptors was explored with ondansetron, a drug which displays a high
affinity at this level, given to 11 OCD patients before intravenous adminis-
tration of m-CPP.40 The findings of this study, showing that m-CPP pro-
voked exacerbation of OCD symptoms and that pretreatment with
ondansetron did not change this response, seem to exclude the involve-
ment of 5-HT3 receptors in OCD, although further data – in particular
comparisons with control groups – are needed.
Intracellular mechanisms
Since a receptor is just the first step of a subsequent cascade of events,
from a biochemical point of view, much interest is focused on the intra-
cellular regulation of the 5-HT transporter and receptors. Some reports
have underlined a link between 5-HT reuptake and protein kinase of
type C (PKC) which inhibits the process,41 and type A, which enhances
5-HT reuptake.42 Protein kinase C belongs to a class of phosphorylases
present at high concentration in the brain.43–45 Diacylglycerol, derived
from the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), stim-
ulates PKC by increasing its affinity for calcium and membrane phos-
pholipids deriving from receptor-mediated hydrolysis and by promoting
its translocation from the cytosol to the particulate fraction.46–48 We inves-
tigated the effect of the activation of PKC on 5-HT reuptake in a group of
patients with OCD compared with a control group, and observed that
the velocity of the reuptake decreased significantly in both OCD patients
and healthy controls, although to a greater degree in OCD patients. This
decrease in Vmax of OCD patients was significantly more robust than in
healthy controls, indicating that the mechanism is ‘more active’ in
OCD.49 This phenomenon could perhaps be attributed either to hyperre-
sponsiveness of the 5-HT reuptake system, or to hyperactivation of PKC
in OCD. Such a latter condition might in turn reflect increased endoge-
nous production of diacylglycerol as a result of a hyperactive phos-
phatidylinositol (PI) pathway. A stimulation of the PI pathway in OCD is
congruent with data showing a worsening of OCD symptoms following
administration of a 5-HT2C receptor agonist such as m-CPP,8,9 a non-spe-
cific a 5-HT2C receptor agonist, and it is well known that 5-HT2C receptors
are linked with a G protein activating phospholipase C.50 However, other
receptors are linked with phospholipase C, including 5-HT2A, dopamine
and muscarinic receptors: interestingly, atypical neuroleptics are ago-
nistic at 5-HT2A receptor level. Hyperactivity of the PI pathway might pro-
voke an alteration in the normal balance existing between the PI
pathway and the cyclic AMP pathway, and increased PKA activity in
OCD patients has been demonstrated.51 There is also evidence of the
therapeutic effect of inositol, a naturally occurring isomer of glucose that
acts as a precursor in the PI pathway in OCD.52 It can, therefore, be
hypothesized that OCD may perhaps be due to an imbalance of the two
main transduction pathways, cAMP and PI, with a prevalence of the sec-
ond and a consequently higher activation of PKC, relative to PKA, given
the cross-talk between the two main second messengers at the level of
different effectors.
Besides the PI pathway, SSRIs and antidepressants have been shown
to upregulate the cAMP–response element binding protein (CREB, a
transcription factor) cascade, as well as the expression of the brain-
derived neurotrophic factor (BDNF).53 Interestingly, CREB is a substrate
for both PKA and PKC, and 5-HT2C agonists seem to influence CREB and
BDNF expression. Therefore, we strongly believe that the elucidation of
these mechanisms will shed new light on disorders such as OCD, where
SSRIs are effective.
Beyond 5-HT
Although the findings implicating 5-HT in the pathophysiology of OCD are

increasing at a level and with a convergence that are not found in any
other psychiatric disorder, the hypothesis that this disorder might be due
to a unique neurochemical abnormality contrasts with the observation
that at least 30% of patients do not respond to SSRIs.1,54 In addition, it is
plausible that the overall clinical heterogeneity of the patients might be
supported by different biological mechanisms. Evidence has been accu-
mulating of disturbances in other neurotransmitters, such as dopamine,
noradrenaline (norepinephrine) and in some neuropeptides in the aetiol-
ogy of OCD: however, in some cases, the findings are meagre and con-
troversial. More agreement exists on the role of immune mechanisms in a
subtype of childhood OCD.
Dopamine
Apart from 5-HT abnormalities, the most consistent findings described in
OCD are those related to the dopamine system. The earliest data derived
from the observation of increased stereotypic behaviours in animals
undergoing manipulation of the dopamine system. Subjects with disor-
ders of the basal ganglia (a dopamine area), such as Gilles de la
Tourette’s syndrome, postencephalitic Parkinson’s or tic syndrome disor-
der, often present with OC symptoms. Cocaine users also suffer from
stereotypic and OC behaviours. These observations have led to the use
of dopamine blockade by typical and atypical neuroleptics as augmenta-
tion strategies in refractory OCD.55
Direct evaluation of peripheral dopamine markers is still very difficult.
We demonstrated an increased activity of platelet sulfotransferase, an
enzyme involved in the catabolism of dopamine, in a group of drug-free
OCD patients, which can reflect an increased level of circulating neuro-
transmitter.17
Noradrenaline
Several studies have reported abnormalities in the noradrenaline system,
based mainly on the positive response of OCD patients to the α2-adrenergic
agonist clonidine.9,56,57 However, evaluation of the role of the noradrenaline
system in OCD by means of challenge tests has been controversial.
An interesting study showed lower CSF concentrations of tyramine and

homovanileic acid in 44 OCD patients than in normal controls or in
patients with Tourette’s syndrome (who also exhibited increased levels of
noradrenaline).58 However, CSF findings, as well as those deriving from
plasma or urine measurements, should be considered with caution given
the low reliability and sensitivity of the methods used.
Neuropeptides
New interest has been directed towards two related neuropeptides, argi-
nine vasopressin and oxytocin, as increased levels have been reported
in patients with pure OCD.59 It has been proposed that the oxytocin
system is involved in the regulation of affiliative behaviours and parental
bonding, and that a disturbance at this level may be related to the patho-
physiology of a specific OCD subtype. Altemus et al showed that
clomipramine increased CSF oxytocin levels in children and adolescents
with OCD.60
Another neuropeptide reported to be more abundant in the CSF of
OCD patients is somatostatin;61 in experimental animals this produces
behaviours resembling compulsive acts.62
Opioid peptides
Amongst other activities, the opioid system is involved in the regulation of
conditioned responses, and it has therefore been hypothesized that it
might have a role in the onset and maintenance of OCD symptoms. A few
clinical observations have suggested the possible usefulness of tra-
madol, a major analgesic, in refractory OCD patients.63,64
Immunological alterations in OCD

There is broad agreement that some forms of childhood OCD may be
due to immunological alterations, on the basis of the possible shared
involvement of basal ganglia abnormalities in OCD and Sydenham’s
chorea, both resulting from infection-driven autoimmune processes.65
Sydenham’s chorea is a manifestation of rheumatic fever, following an
infection provoked by group A β-haemolytic streptococci, which is
thought to derive from the production of antibodies cross-reacting with
neurons of the basal ganglia.66 The relationship between OCD and
Sydenham’s chorea is strengthened by clinical observations showing that
more than 80% of children with the latter condition show obsessions and
compulsions both before and concomitantly with, choreic movements,67
and that one-third of OCD children present with choreiform movements.68
As a result, the hypothesis has emerged that infections with group A β-
haemolytic streptococci might produce conditions grouped together
under the acronym PANDAS (Paediatric Autoimmune Neuropsychiatric

Disorders Associated with Streptococci), including subtypes of paedi-
atric OCD and tics.69,70 However, the observation has been made that
even viral infections might trigger the autoimmune process leading to
OCD.71,72 Furthermore, patients with rheumatic fever show a high level of
antineural antibodies against the caudate nucleus,73 and a particular anti-
gen in B lymphocytes reacting with a monoclonal antibody, D8/D17.74,75
Such an antigen has been shown to be stable in different populations
and over time; more interestingly, it is also present in patients with child-
hood OCD, Tourette’s syndrome and chronic tic disorder.76 Preliminary
data also indicate its presence in subjects with autism.77 Although the
relationship between the antigen identified by the D8/17 antibody and the
pathophysiology of the various disorders is not yet clear, it has been con-
sidered either to be an immunological marker of susceptibility to
rheumatic fever,75 or to be linked to the motor component of the various
disturbances.78
The literature regarding immunological factors in adult OCD is sparse.
Cytokine production appears to be normal in OCD patients, at variance
with depressed patients.79 Barber et al evaluated T-lymphocyte subsets
in chronic OCD patients in the acute phase, but were unable to find any
difference in comparison with healthy controls, either before or after suc-
cessful clomipramine treatment.80 On the other hand, the possible
involvement of the immune system in some subtypes of OCD is sup-
ported by the finding of a relationship between the severity of the disor-
der and interleukin-6 (IL-6) and IL-6 receptor levels81 and by the
observation of decreased concentrations of plasma cytokines, such as
interleukin-1β and tumour necrosis factor-α,82 related to hyperactivity of
the noradrenergic system and of the hypothalamus–pituitary–adrenal
(HPA) axis. Increased levels of cells carrying the CD8⫹ antigen and
decreased levels of those carrying – i.e. suppressor and helper lympho-
cytes, respectively, have been demonstrated in adult OCD patients.83
The role of immune factors in OCD is also supported by the report of
increased CSF levels of immunoglobulin G antibodies against herpes
virus type 1 suggestive of a chronic infection, in a sample of adult
patients,72 but the specificity of these findings needs to be clarified.
All these observations are intriguing, but much research remains to be
done. In particular, it would be helpful to identify familial, clinical or symp-
tomatological features that might be linked to immunological distur-
bances. The presence of such disturbances suggests the use of
non-conventional treatments, in particular antibiotics or immunomodula-
tors;67,71 however, the results of the first pilot study of penicillin prophy-
laxis in children with PANDAS were negative.84
Conclusion
Considerable advances have been made in the understanding of the
pathogenesis of OCD. A wealth of evidence in favour of abnormalities of
the 5-HT system has, however, led to the notion that ‘the best is yet to
come’.85 That is, if the role of 5-HT is undoubted, there are a number of
open questions related to the serotonergic system still to be answered.
Are the serotonergic disturbances primary or secondary? Are they
involved in the pathophysiological chain or only in the phamacological
response? In addition, the serotonergic abnormalities found in OCD have
been reported also in other psychiatric conditions and therefore cannot
be considered nosologically specific, but rather linked to a dimension (or
dimensions) cutting across different diagnostic entities. Although much
research is still required, some authors have already highlighted relation-
ships between the 5-HT transporter and personality traits,86 aggressive
features,87 anxiety traits,88 and the overvalued ideation typical of the early,
romantic phase of a love relationship.89 In addition, if the successful use
of SSRIs has highlighted the key role of the 5-HT transporter, latest devel-
opments in the mode of action of these drugs suggest the involvement of
different 5-HT receptor subtypes yet to be identified and, probably, of
second messengers. Taken together, these findings suggest further pos-
sibilities in the treatment of OCD through the modulation of new therapeu-
tic targets. Thus, compounds acting on specific 5-HT receptor subtypes,
such as the 5-HT2A, 5-HT2C, 5-HT5A receptors and probably others, or
compounds that inhibit PKC, potentiate PKA or act on various G-protein
subunits, seem to represent potential antiobsessive drugs.
The role of other neurotransmitters has not been deeply explored,
mainly because of the lack of sensitive and reliable research tools; never-
theless, the role of noradrenaline, dopamine and some peptides
deserves further investigation.
Disturbances of the immune system continue to be reported in some
OCD subtypes – particularly in the childhood form, although data also
indicate immune dysregulations in adult OCD. Immunological alterations
appear to be different in children and in adults, probably reflecting differ-
ent pathophysiological mechanisms such as autoimmune and possibly
primary processes in children, and perhaps secondary alterations in
adulthood. The immunological disturbances may be also related to
specific dimensions, as a correlation between the antigen D8/17 and
repetitive behaviours in autistic subjects has been reported.77
In conclusion, the availability of research data from a number of
sources has served to underline the complexities of OCD, which appears
to be heterogeneous not only clinically but also in terms of its patho-
physiological mechanisms. Probably there exist multiple causes with the
ability to trigger OCD symptoms according to individual vulnerability
(genetically based?) or exposure to certain agents (infections?), with
prevalence varying at different ages. The involvement of various neuro-

transmitters/neuroreceptors and circuitries and the balance between
them might provide an explanation of the presence of more or less
obsessions or compulsions or both, or of one type of obsession or com-
pulsion over another.
Alternatively, the neurochemical imbalance may produce disturbances
in dimensions yet to be identified that might explain the overlapping of
symptoms and the common drug response observed in various psychi-
atric conditions. Without doubt, the identification of these common
dimensions that constitute the ‘core’ feature of the disorder, will constitute
an intriguing area for future research.
References
1 Montgomery SA, Pharmacologi- Clomipramine treatment of obses-
cal treatment of obsessive-com- sive disorder: biochemical and
pulsive disorder. In: Hollander clinical aspects, Psychopharma-
E, Zohar J, Marazziti D, Olivier col Bull (1981) 18:13–21.
B, eds, Current Insights in 8 Zohar J, Insel TR, Obsessive-
Obsessive-compulsive Disorder compulsive disorder: psychobio-
(John Wiley: Chichester, 1994) logical approaches to diagnosis,
215–26. treatment and pathophysiology,
2 Piccinelli M, Pini S, Bellantuono C, Biol Psychiatry (1987) 22:667–87.
Wilkinson C, Efficacy of drug 9 Hollander E, Fay M, Cohen B et
treatment in obsessive-compul- al, Serotonergic and noradrener-
sive disorder, Br J Psychiatry gic sensitivity in obsessive-com-
(1995) 166:424–43. pulsive disorder: behavioral
3 Greist JH, Jefferson JW, Kobak findings, Arch Gen Psychiatry
KH et al, Efficacy and tolerability (1988) 145:1015–23.
of serotonin transport inhibitors in 10 Zohar J, Insel TR, Zohar-Kadouch
obsessive-compulsive disorder, RC, Hill J, Murphy DL, Serotoner-
Arch Gen Psychiatry (1995) gic responsivity in obsessive-com-
52:53–60. pulsive disorder. Effect of chronic
4 Fineberg N, Refining treatment clomipramine treatment, Arch Gen
approaches in obsessive-compul- Psychiatry (1988) 45:167–72.
sive disorder, J Clin Psychophar- 11 Lesch KP, Wolozin BL, Murphy
macol (1996) 11:(suppl. 5) 13–22. DL, Riederer P, Primary structure
5 Insel TR, Mueller EA, Alterman I et of the human platelet serotonin
al, Obsessive-compulsive disor- uptake: identity with the brain
der and serotonin: is there a con- serotonin transporter, J Neuro-
nection? Biol Psychiatry (1985) chem (1993) 60:2319–22.
20:1174–88. 12 Rausch JJ, Hutchinson J, Li X,
6 Thoren P, Asberg M, Cronholm B, Correlations of drug action
Clomipramine treatment of obses- between human platelets and
sive-compulsive disorder: a con- human brain 5HT, Biol Psychiatry
trolled clinical trial, Arch Gen (1995) 137(suppl.):600.
Psychiatry (1980) 37:1281–9. 13 Meyerson LR, Ieni JR, Wennogle
7 Asberg M, Thoren P, Bertilsson L, LP, Allosteric interaction between
the site labelled by 3H-imipramine paroxetine and 3H-imipramine to

and the serotonin transporter in human platelet membranes, Eur J
human platelets, J Neurochem Pharmacol (1983) 96:303–9.
(1987) 48:560–5. 23 Marazziti D, Rossi A, Gemignani,
14 Hrdina PD, Differences between G et al, Decreased 3H-paroxetine
sodium-dependent and desi- binding in obsessive-compulsive
pramine-defined 3H-imipramine patients, Neuropsychobiology
binding in intact human (1996) 34:184–7.
platelets, Biol Psychiatry (1989) 24 Sallee FR, Richman H, Beach K et
25:576–84. al, Platelet serotonin transporter in
15 Marcusson JO, Fowler CJ, Hall H children and adolescents with
et al, ‘Specific’ binding of 3H- obsessive-compulsive disorder or
imipramine to protease-sensitive Tourette’s syndrome, J Am Acad
and protease-resistant sites, J Child Adolesc Psych (1996) 35:
Neurochem (1985) 44:705–11. 1647–56.
16 Weizman R, Carmi M, Hermesh H 25 Hollander E, DeCaria C, Wong
et al, High-affinity imipramine CM, Aronowitz B, Predictors of
binding and serotonin uptake in SSRI treatment response in OCD
platelets of eight adolescent and and autism. Paper presented at
ten adult obsessive-compulsive the XXI CNP Congress, Glasgow,
patients, Am J Psychiatry (1986) 12–16 July 1998, abstract 191.
143:335–9. 26 Zohar Y, Sasson Y, Chopra M,
17 Marazziti D, Hollander E, Lensi P Groos R, Predictors of response
et al, Peripheral markers of sero- in OCD. Paper presented at the
tonin and dopamine function in XXI CNP Congress, Glasgow,
obsessive-compulsive disorder, 12–16 July 1998, abstract 191.
Psychiatry Res (1992) 42:41–51. 27 Marazziti D, Predictors of
18 Black DW, Kelly M, Myers C, response, Eur Neuropsychophar-
Noyes R, Tritiated imipramine macol (1997) 27(suppl. 2): 101–2.
binding in obsessive-compulsive 28 Hoyer D, Martin G, 5-HT receptor
volunteers and psychiatrically classification and nomenclature:
normal controls, Biol Psychiatry towards a harmonization with the
(1990) 27:319–27. human genome, Neuropharma-
19 Bastani B, Arora RC, Meltzer HY, cology (1997) 36:419–28.
Serotonin uptake and imipramine 29 Blier P, De Montigny C, Possible
binding in the blood platelets of serotonergic mechanisms under-
obsessive-compulsive disorder lying the antidepressant and anti-
patients, Biol Psychiatry (1991) obsessive-compulsive disorder
30:131–9. responses, Biol Psychiatry (1998)
20 Vitiello B, Shimon H, Behar D et 44:312–23.
al, Platelet imipramine binding 30 Benkefalt C, Murphy DL, Zohar J
and serotonin uptake in obses- et al, Clomipramine in obsessive-
sive-compulsive patients, Acta compulsive disorder: further evi-
Psychiatr Scand (1991) 84:29–32. dence for a serotonergic
21 Mann CD, Hrdina PPD, Sodium mechanism of action, Arch Gen
dependence of 3H-paroxetine Psychiatry (1989) 46:23–8.
binding and 5-3H-hydroxytrypta- 31 Erzegovesi S, Ronchi P, Smeraldi
mine uptake in rat diencephalon, E, 5-HT2 receptor and fluvoxam-
J Neurochem (1992) 59:1856–61. ine in obsessive-compulsive dis-
22 Mellerup ET, Plenge P, Engelstoft order, Hum Psychopharmacol
M, High-affinity binding of 3H- (1992) 7:287–9.
32 Moreno FA, Delgado PL, Hallu- Acute intravenous administration

cinogen-induced relief of obses- of ondansetron and m-CPP, alone
sions and compulsions, Am J and in combination, in patients
Psychiatry (1997) 145:1037–8. with obsessive-compulsive disor-
33 McDougle CJ, Update on phar- der (OCD): behavioral and bio-
macologic management of OCD: logical results, Psychiatr Res
agents and augmentation, J Clin (1998) 79:11–20.
Psychiatry (1997) 58(suppl 12): 41 Anderson G, Horne WC, Activa-
11–17. tors of protein kinase C decrease
34 Pigott TA, Zohar J, Hill JL et al, serotonin transport in human
Metergoline blocks the behav- platelets, Biochim Biophys Acta
ioral and neuroendocrine (1992) 1137:331–7.
effects of orally administered 42 De Vivo M, Maayani S, Inhibition
m-chlorophenylpiperazine in of forskolin stimulation adenylate
patients with obsessive-compul- cyclase activity by 5-HT receptor
sive disorder, Biol Psychiatry agonist, Eur J Pharmacol (1985)
(1991) 29:418–26. 119(3):231–4
35 Bastani B, Nash F, Meltzer H, Pro- 43 Nishizuka Y, Studies and per-
lactin and cortisol response to spective of protein kinase C, Sci-
MK-212, a serotonin agonist, in ence (1986) 233:305–12.
obsessive-compulsive disorder, 44 Kikkawa U, Kishimoto A,
Arch Gen Psychiatry (1990) Nishizuka Y, The protein kinase C
47:946–51. family: heterogeneity and its
36 Stern L, Zohar J, Hendler T et al, implications, Ann Rev Biochem
The potential role of 5-HT1D (1989) 58:31–44.
receptors in the pathophysiology 45 Wilkinson SE, Hallam TJ, Protein
of obsessive-compulsive disor- kinase C: is pivotal role in cellular
der. CNS Spectrum (1998) activation over-stated? TIPS
3(8):46–9 (1994) 15:53–7.
37 Ho Pian KL, Westenberg HGM, 46 Berridge MJ, Downes CP, Hanley
van Megen HJGM, Den Boer JA, MR, Lithium amplifies agonist-
Sumatriptan (5-HT1D receptor dependent phosphatidylinositol
agonist) does not exacerbate responses in brain and salivary
symptoms in obsessive-compul- glands, Biochem J (1982)
sive disorder, Psychopharmacol- 206:587–95.
ogy (1998) 140:365–70. 47 Ashendel CL, The phorbol ester
38 Lesch KP, Hoh A, Disselkamp- receptor: a phospholipid-regu-
Tietze J et al, 5-Hydroxytrypta- lated protein kinase, Biochim Bio-
mine1A receptor activity in phys Acta (1985) 822:219–42.
obsessive-compulsive disorder: 48 Weiss S, Ellis J, Hendley DD,
comparison of patients and con- Lenox RH, Translocation and acti-
trols, Arch Gen Psychiatry (1991) vation of protein kinase C in stri-
48:540–7. atal neurons in primary culture:
39 McDougle CJ, Goodman WK, relationship to phorbol dibutyrate
Leckman JF et al, Limited thera- actions on the inositol phosphate
peutic efficacy of addition of bus- generating system and neuro-
pirone in fluvoxamine-refractory transmitter release, J Neurochem
obsessive-compulsive disorder, (1989) 52:530–6.
Am J Psychiatry (1993) 150: 49 Marazziti D, Rossi A, Masala I et
647–9. al, Regulation of the platelet sero-
40 Broock A, Pigott TA, Hill JL et al, tonin transporter by protein
kinase C in the young and elderly, Tourette’s syndrome, and healthy

Biol Psychiatry (1999) 45:443–7. controls, Neuropsychopharmacol-
50 Wang HY, Friedman E, Central 5- ogy (1995) 12:73–86.
Hydroxytryptamine receptor- 59 Leckman JF, Goodman WK,
linked protein kinase C North WG et al, Elevated levels of
translocation: a postfunctional CSF oxytocin in obsessive-com-
postsynaptic signal transduction pulsive disorder: Comparison with
system, Mol Pharmacol (1989) Tourette’s syndrome and healthy
37:75–9. controls, Arch Gen Psychiatry
51 Perez J, Tardito D, Ravizza L, (1994) 51:782–92.
Racagni G, Mori S, Maina G, 60 Altemus M, Swedo SE, Leonard B
Altered cAMP-dependent protein et al, Changes in cerebrospinal
kinase in platelets of patients with fluid neurochemistry during treat-
obsessive-compulsive disorder, ment of obsessive-compulsive dis-
Am J Psychiatry (2000) 157: order with clomipramine, Arch Gen
284–6. Psychiatry (1994) 51:794–803.
52 Fux M, Levine J, Aviv A, Belmaker 61 Altemus M, Pigott T, L’Hereux F et
RH, Inositol treatment of obses- al, Cerebrospinal fluid somato-
sive-compulsive disorder, Am J statin in obsessive-compulsive
Psychiatry (1996) 153:1219–21. disorder, Am J Psychiatry (1993)
53 Duman RS, Novel therapeutic 15:460–4.
approaches beyond the serotonin 62 Pitman RK, Animal models of
receptor, Biol Psychiatry (1998) compulsive behaviour, Biol Psy-
44:324–35. chiatry (1989) 26:189–98.
54 Sasson Y, Zohar Y, New develop- 63 Shapira NA, Goldsmith TD, Keck
ments in obsessive-compulsive PE, Open label study of tramadol
disorder research: implications hydrochloride in treatment-refrac-
for clinical management, J tory obsessive-compulsive disor-
Clin Psychopharmacol (1996) der, Depress Anx (1997) 6:170–3.
11(suppl. 5): 3–12.
64 Goldsmith TD, Shapira NA, Keck
55 McDougle J, Goodman WK, Price PE, Rapid remission of OCD with
LK et al, Neuroleptic addition in tramadol hydrochloride, Am J
fluvoxamine-refractory obsessive-
Psychiatry (1999) 156:660–1.
compulsive disorder, Am J Psy-
chiatry (1990) 150:647–9. 65 Swedo SE, Sydenham’s chorea: a
model for autoimmune neuropsy-
56 Knesevich JW, Successful treat-
chiatric disorders, JAMA (1994)
ment of obsessive-compulsive
272:1788–91.
disorder with clonidine hydrochlo-
ride, Am J Psychiatry (1982) 66 Bronze MS, Dale JB, Epitopes of
139:360–5. streptococcal M proteins that
57 Hollander E, De Caria C, Nitescu evoke antibodies that cross-react
A et al, Noradrenergic function in with human brain, J Immunol
obsessive-compulsive disorder: (1993) 151:2820–8.
behavioral and neuroendocrine 67 Swedo SE, Leonard HL, Kiessling
responses to clonidine and com- LS, Speculations on antineuronal
parison to healthy controls, Psy- antibody-mediated neuropsychi-
chiatr Res (1991) 37:161–77. atric disorders of childhood, Pedi-
58 Leckman JF, Goodman WK, atrics (1994) 93:323–6.
Anderson GM et al, Cerebro- 68 Denckla MB, Rapoport JL, Neuro-
spinal fluid biogenic amines in logical examination. In: Denckla
obsessive-compulsive disorder, MB, Rapoport JL, eds, Obses-
sive-compulsive Disorder in Chil- MW et al, B Lymphocyte antigen

dren and Adolescents (American D8/17: a peripheral marker for
Psychiatric Press: Washington childhood-onset obsessive-com-
DC, 1989) 107–18. pulsive disorder and Tourette’s
69 Swedo SE, Leonard HL, Mittle- syndrome? Am J Psychiatry
man B et al, Identification of chil- (1997) 154: 3:402–7.
dren with paediatric autoimmune 77 Hollander E, DelGiudice G, Simon
neuropsychiatric disorders asso- L et al, B lymphocyte D8/17 and
ciated with streptococcal infec- repetitive behavior in autism, Am
tions by a marker associated with J Psychiatry (1999) 156:317–20.
rheumatic fever, Am J Psychiatry 78 Kiessling LS, Marcotte AC,
(1997) 154:110–12. Culpepper L, Antineuronal anti-
70 Swedo SE, Leonard HL, Garvey bodies in movement disorders,
M et al, Paediatric Autoimmune Pediatrics (1993) 92:39–43.
Neuropsychiatric Disorders asso- 79 Weizman R, Laor N, Barber Y et
ciated with Streptococcal Infec- al, Cytokine production in obses-
tions (PANDAS): a clinical sive-compulsive disorder, Biol
description of the first fifty cases, Psychiatry (1996) 40:908–12.
Am J Psychiatry (1998) 55: 80 Barber Y, Toren P, Achiron A et
264–71. al, T cell subsets in obsessive-
71 Allen AJ, Leonard HL, Swedo SE, compulsive disorder, Neuro-
Case study: a new infection-trig- psychobiology (1996) 34:63–6.
gered autoimmune subtype of 81 Maes M, Meltzer HY, Bosnan E,
pediatric OCD and Tourette’s Psychoimmune investigation in
syndrome, J Am Acad Child Ado- obsessive-compulsive disorder:
lesc Psych (1995) 34:307–11. assay of plasma transferrin, IL-β
72 Khanna S, Ravi V, Shenoy PK et and IL-6 receptors, and IL-1β
al, Cerebrospinal fluid viral anti- and IL-6 concentrations, Neuro-
bodies in obsessive-compulsive psychobiology (1994) 30:57–60.
disorder in an Indian population, 82 Brambilla F, Perna G, Bellodi L et
Biol Psychiatry (1997) 41: al, Plasma interleukin 1 beta and
883–90. tumor necrosis factor concentra-
73 Husby G, van den Rijn I, tions in obsessive-compulsive
Zabriskie JB et al, Antibodies disorder, Biol Psychiatry (1997)
reacting with cytoplasm of sub- 42:976–81.
thalamic and caudate nuclei neu- 83 Marazziti D, Presta S, Pfanner C
rons in chorea and acute et al, Immunological alterations in
rheumatic fever, J Exp Med adult obsessive-compulsive dis-
(1976) 144:1094–110. order, Biol Psychiatry (1999) 46:
74 Zabriskie JB, Rheumatic fever: a 810–14.
model for the pathological conse- 84 Garvey MA, Perlmutter SJ, Allen
quences of microbial-host mim- AJ et al, A pilot study of penicillin
icry, J Clin Exp Rheumatol (1986) prophylaxis for neuropsychiatric
4:65–73. exacerbation triggered by strep-
75 Gibofsky A, Khanna A, Suh E, tococcal infections, Biol Psychia-
Zabriskie JB, The genetics of try (1999) 45:1564–71.
rheumatic fever: relationship to 85 Greden JF, Serotonin: how much
streptococcal infection and we have learned! So much to dis-
autoimmune disease, J Rheuma- cover, Biol Psychiatry (1998) 44:
tol (1991) 18(suppl. 30): 1–5. 309–11.
76 Murphy TK, Goodman WK, Fudge 86 Lesch KP, Benge D, Heils A et al,
Association of anxiety-related 88 Coccaro EF, Kavoussi RJ, Sheline

traits with a polymorphism in the YI et al, Impulsive aggression in
serotonin transporter gene regu- personality disorder correlates
latory region, Science (1996); with tritiated paroxetine binding in
274:1527–31. the platelets, Arch Gen Psychiatry
87 Mazzanti C, Lappalainen J, Long (1996) 53:531–6.
JC et al, Role of the serotonin 89 Marazziti D, Akiskal HS, Rossi A,
transporter promoter polymor- Cassano GB, Alteration of the
phism in anxiety-related traits, platelet serotonin transporter in
Arch Gen Psychiatry (1998) 55: romantic love, Psychol Med
936–40. (1999) 29:741–5.
9
Practical pharmacotherapy
Joseph Zohar and Naomi Fineberg
Before 1980, the prognosis for obsessive compulsive disorder (OCD)

was poor. The discovery of effective drug therapies revolutionized the
outlook for sufferers, and paved the way for research into the neuro-
biology of OCD. In this chapter we attempt to answer the key clinical
questions concerning drug treatment of OCD as far as possible using
evidence derived from randomized, controlled trials (Table 9.1).
The serotonin hypothesis

Intensive pharmacological investigation has demonstrated that OCD
responds selectively to drugs that act as potent inhibitors of the synaptic
reuptake of serotonin (serotonin reuptake inhibitors, SRIs) – that is,
clomipramine and the selective SRIs (Table 9.2). Drugs lacking these
properties, such as the standard tricyclic antidepressants amitriptyline,
desipramine and nortriptyline, and the monoamine oxidase inhibitors
clorgyline and phenelzine, have been shown to be ineffective in random-
ized, controlled trials.1,2 Studies looking at benzodiazepines, lithium and
electroconvulsive therapy have not produced positive findings (reviewed
by Zohar et al).3 Antipsychotics also appear ineffective on their own,
although they may have a role as agents of augmentation in cases where
the response to the SRI is incomplete (see Chapter 11) or when a combi-
nation of OCD and tic disorder is present.
Table 9.1 Practical questions for OCD pharmacotherapy.

• What kind of drug?
• What dose?
• What are the side effects?
• What about comorbidity?
• How long should treatment continue, and what happens if treatment is
discontinued?
103
Table 9.2 The pharmacological specificity of OCD.

Effective as monotherapy
Potent SRIs such as clomipramine, fluvoxamine, fluoxetine, sertraline, paroxetine
and citalopram
Potential as agents of augmentation in combination with SRIs
Conventional antipsychotics such as haloperidola
Atypical antipsychotics such as risperidone,b olanzapinec
Pindolold
Ineffective
Tricyclic antidepressants (apart from clomipramine)
Monoamine oxidase inhibitors
Lithium
Benzodiazepines
Buspirone
Electroconvulsive therapy
a
Effective in OCD with comorbid tics.4
b
Effective in the absence of comorbid tics.5
c
Efficacy not yet established in controlled studies.
d
Positive and negative findings from controlled studies.6,7
The selectivity of the pharmacological response distinguishes OCD

from the other anxiety disorders and from depression in which both nor-
adrenergic and serotonergic medications appear to be equally potent.
Although the pharmacological data indicate a role for serotonin in the
pathophysiology of OCD, neurobiological research has failed to produce
consistent findings. It appears increasingly unlikely that the illness results
from a specific abnormality in serotonin neurotransmission, and there
may well be a variety of different biochemical abnormalities underpinning
the disorder.
If this is the case, why then are the SRIs uniquely effective? Serotonin
is understood to play an important role in modulating stress. Instead of
repairing a specific serotonergic lesion, it is possible that the SRIs work
in OCD by enhancing fundamental neuropsychological defence systems,
which rely on serotonin activity to function adequately.8
Clomipramine: the first effective drug for OCD
The discovery that clomipramine is an effective treatment for OCD was

an important breakthrough. Clomipramine can be distinguished from the
other tricyclic drugs by its more powerful SRI activity, although its effects
are not exclusively serotonergic. The first reports of the successful treat-
ment of OCD by clomipramine appeared as early as the 1960s.9,10 The
seminal study by Montgomery specifically excluded depressed individu-
Practical pharmacotherapy 105
als and demonstrated efficacy against placebo using a relatively modest

fixed daily dose (75 mg) in a small, carefully selected group.11 Later,
larger studies confirmed that daily doses of up to 300 mg were effective
in adults and children, both in the presence and absence of depression
(reviewed by Zohar et al).3 It is now established beyond doubt that the
antiobsessional effect of clomipramine does not depend upon an anti-
depressant effect.
Characteristics of the drug effect
Obsessive compulsive disorder shows a slow, gradual improvement

which starts within a few days of the initiation of treatment and continues
for months thereafter. These characteristics were demonstrated most
clearly in the treatment-naive populations entering the early clomipramine
studies. In large multicentre studies of clomipramine,12 there was a
40–45% improvement measured by the Yale–Brown Obsessive Compul-
sive Scale (Y-BOCS, see Appendix 1, p. 183)13 by the 10-week end-point.
This represented a considerable functional improvement, involving sub-
stantial reductions in time spent on obsessions and compulsions.
Extension studies in OCD have shown that gains continue to be made
for at least 2 years as long as treatment is continued, and patients need
to be encouraged to persevere during the early stages when progress
can seem frustratingly slow.
Selective SRIs
Efficacy compared with clomipramine

Convincing evidence from large-scale randomized, placebo-controlled
studies supports the efficacy of fluvoxamine, fluoxetine, sertraline, parox-
etine and citalopram in OCD (reviewed by Zohar et al).3 The size of the
treatment effect reported for the selective serotonin reuptake inhibitors
(SSRIs) was smaller than that reported in the earlier trials of clomipramine
– probably because the early studies included fewer treatment-resistant
cases. Claims that clomipramine shows stronger efficacy (by, for exam-
ple, Piccinelli et al)14 have been challenged by the results from controlled
comparator studies (Table 9.3). Many of these studies were underpow-
ered,25 but the trial by Bisserbe et al was large enough to show a signifi-
cant advantage for sertraline over (low-dose) clomipramine,23 and since
the advantage was only for some efficacy measures and only in the
intent-to-treat group, the superiority is not clear-cut. Even larger studies
showed equivalent efficacy for clomipramine and paroxetine.21,22
Table 9.3 Comparing SSRIs with clomipramine: controlled studies.
Study No. Design Outcome
Fluoxetine
Piggott et al (1990)15 11 CMI vs FLX CMI ⫽ FLX
Lopez-Ibor et al (1996)16 55 CMI vs FLX CMI ⫽ FLX on primary criterion
CMI > FLX on other criteria
Fluvoxamine
Smeraldi et al (1992)17 10 CMI vs FLV CMI ⫽ FLV
Freeman et al (1994)18 64 CMI vs FLV CMI ⫽ FLV
Koran et al (1996)19 42 CMI vs FLV CMI ⫽ FLV
37
Milanfranchi et al (1997)20 26 CMI vs FLV CMI ⫽ FLV
Rouillon (1998)21 105 CMI vs FLV CMI ⫽ FLV
112
Paroxetine
Zohar and Judge (1996)22 99 CMI CMI > Placebo
201 vs PAR PAR > Placebo
99 vs Placebo
Sertraline
Bisserbe et al (1997)23 82 CMI SER ⫽ CMI
86 vs SER
Citalopram
Pidrman and Tuma (1998)24 24 CIT vs CMI CIT ⫽ CMI
CIT, citalopram; CMI, clomipramine; FLV, fluvoxamine; FLX, fluoxetine; PAR, paroxetine; SER, sertraline.
SSRIs as first-line treatment for OCD

In the face of equivalent efficacy, the choice of SRI depends to a large
extent on the side-effect profile of the compound. An important advan-
tage of the SSRIs over clomipramine lies in their greater acceptability.
The risk of dangerous side effects such as convulsions (occurring in up
to 2% patients on clomipramine, 0.1–0.5% patients on higher-dose
SSRIs), cardiotoxicity and cognitive impairment is substantially lower on
SSRIs. Clomipramine shares the unpalatable side effects associated with
the older tricyclics, including dry mouth, constipation, weight gain and
blurred vision. The SSRIs are better tolerated, although they are responsi-
ble for more asthenia, insomnia and nausea. Whereas all SRIs are asso-
ciated with impaired sexual performance, clomipramine (up to 80% of
cases) is worse than the SSRIs (up to 30% of cases) in this respect. In
the comparator studies, the drop-out rate for adverse effects on
clomipramine (around 17%) was consistently higher than that for the
SSRIs (around 9%). In fact, the greater tolerability of sertraline was
thought to have explained its superior effect on the intent-to-treat analysis
in the comparator study by Bisserbe et al (Table 9.3).23
Improved safety and tolerability and lower rates of premature discon-
tinuation offer considerable benefits for long-term treatment, and indicate
that the SSRIs should be considered the treatment of choice, with
clomipramine reserved as a second-line treatment for those who cannot
tolerate SSRIs or who have failed to respond to them.
Differences between SSRIs

Choosing between SSRIs is difficult because their effects are so similar.
In the absence of comparator data, the selection of a drug largely
depends upon personal preference. Occasionally the possibility of a
drug interaction influences the choice. Sertraline and citalopram are rela-
tively weak inhibitors of the hepatic cytochrome P450 enzymes which
metabolize commonly prescribed drugs, and may be preferred if drug
interactions are likely to be a problem. Fluoxetine and paroxetine are
powerful inhibitors of the CYP 2D6 isoenzyme, which metabolizes tri-
cyclic antidepressants, antipsychotics, antiarrhythmics and beta-
blockers. Fluvoxamine inhibits both CYP 1A2, which eliminates warfarin
and tricyclics, and CYP 3A4, which metabolizes benzodiazepines and
some antiarrhythmics. Fluoxetine has a long half-life and an active
metabolite resulting in fewer withdrawal effects, which can be advanta-
geous for patients who forget to take their tablets.
Comorbid depression
Obsessive compulsive disorder is commonly complicated by comorbid
depression, and roughly one-third of patients presenting for treatment are
concurrently depressed. Comorbid OCD has received little investigation
because most treatment studies have attempted to exclude depressed
patients to keep the sample ‘pure’. Moderate levels of depression do not
appear to interfere with the antiobsessional response to SRI treatment.22
Comorbid depression responds together with the OCD, sharing its char-
acteristic selectivity for serotonergic antidepressants.26
Unlike drug treatment, studies looking at behaviour therapy have
shown that moderately high levels of baseline depression adversely
affect the outcome of treatment.27 It has been suggested that this disad-
vantage may be neutralized by augmenting the behaviour therapy with
an SSRI,28 although the studies looking at this area have not been able to
disentangle the antiobsessional effects of the medication from those of
the behavioural intervention. These findings suggest that for depressed
patients with OCD the first-line treatment should be with an SRI.
Dosage
What is the most effective dose for OCD?

In order to answer this question studies need to compare multiple fixed
doses of the active drug, preferably also with placebo (Table 9.4).29 Nei-
ther clomipramine nor fluvoxamine have been examined in this way,
although the results from the study by Montgomery suggest that 75 mg
clomipramine is the minimum effective dose.11 Fixed-dose studies have
been performed for paroxetine, fluoxetine, sertraline and citalopram. In
the case of paroxetine, a positive dose–response relationship was clearly
demonstrated; the 40 mg and 60 mg daily doses showed efficacy while
the 20 mg dose did not differ from placebo.33 The fluoxetine studies pro-
duced similar results: whereas all three fixed doses (20 mg, 40 mg,
60 mg) were effective, there was a trend toward greater improvement in
the group receiving 60 mg a day, which became significant when data
were pooled from more than one study centre.31,35 There is another clear
suggestion of a dose–response relationship for fluoxetine, with the 20 mg
daily dose producing an effect no different from placebo, while the 40 mg
and 60 mg doses produced the best effect.30
The results for sertraline are not clear. In a study that has been criticized
for lack of statistical power, the 50 mg and 200 mg doses were superior to
placebo, whereas the 100 mg dose was not.32 In the preliminary report of a
fixed-dose study, 20 mg of citalopram were found to be effective, with a
suggestion of increasing effect over time with increasing dose.34
Table 9.4 Placebo-controlled fixed-dose studies in OCD.
Study Fixed dose (mg) N Duration (weeks) Positive dose–response relationship?
Fluoxetine
Montgomery et al (1993)30 20/40/60 214 8 Yesa
Tollefson et al (1994)31 20/40/60 355 13 No
Sertraline
Greist et al (1995)32 50/100/200 324 12 No
Paroxetine
Wheadon et al (1993)33 20/40/60 348 12 Yes
Citalopram
Montgomery (1998)34 20/40/60 352 12 Yesb
a
Marginally significant benefit for medium and higher doses on primary analysis (total Y-BOCS, see Appendix 1, p. 183), p ⫽ 0.059; significant on ‘responder’ analysis
(p < 0.05).
These results have been interpreted to suggest that the higher dose
levels (e.g. 40–60 mg of fluoxetine, paroxetine or citalopram) are associ-
ated with better antiobsessional efficacy. Some experts use even higher
doses, particularly in resistant cases, but in the absence of controlled
data this practice cannot be recommended without reservation.
Dose titration: the key to effective pharmacotherapy

Improvements in OCD take several weeks to become established, irre-
spective of the dose, and it is helpful to warn patients about this from the
outset. Gastrointestinal symptoms often occur in the first days of SSRI
treatment and are usually short-lived; they can be ameliorated by starting
at the lower dose levels and slowly titrating upwards, monitoring for
longer-term side effects such as sleep disturbance and headache, which
may become more prominent as the dose increases. Sexual function
should be carefully monitored, and if necessary strategies such as med-
ication to restore potency (e.g. sildenafil, mianserin, cyproheptadine,36)
dose reduction or short ‘drug holidays’ can be considered if the patient is
stable.
Sufferers from OCD are notoriously poor at recognizing their own
improvements. Systematic use of observer-rated scales such as the
Y-BOCS13 (see Appendix 1, p. 183) and the assistance of reliable infor-
mants can be invaluable in the clinical setting.
Is treatment effective over the longer term?

Because OCD is a long-term illness, we need to be confident that the
treatment effect endures. Evidence for long-term efficacy can be derived
from a variety of sources. Some investigators have taken treatment
responders from acute-phase studies and followed them on ‘uncon-
trolled’ SRI for up to 2 years, with the result that the response has
increased over time without tolerance developing.37 A study by Wagner
et al demonstrated ongoing efficacy and tolerability for open-label sertra-
line, up to 1 year, in a large cohort of children and adolescents.38
The evidence from controlled studies is more convincing. Cottraux et al
found that fluvoxamine continued to show superiority over placebo, in the
face of concomitant behaviour therapy in both groups, after 6 months of
double-blind treatment (Table 9.5).39
A small number of studies have followed treatment responders for up
to 1 year under double-blind, placebo-controlled conditions, and have
found that the treatment effect was sustained (Table 9.5). Patients contin-
ued to improve on active treatment, whereas those remaining on placebo
did not. In the large extension study by Greist et al,41 118 patients who
had responded to 12 weeks’ treatment with either sertraline or placebo
Table 9.5 Placebo-controlled continuation studies in OCD.

Author Active treatment No. Duration (weeks)
Cottraux et al (1990)39 Fluvoxamine ⫹ exposurea 50 8

44 24
37 48
Katz et al (1990)40 Clomipramineb 110 [10⫹] 52
Tollefson et al (1994)31 Fluoxetineb 76 [13⫹] 24
Greist et al (1995)41 Sertralineb 118 [12⫹] 40
a
Extended double-blind study.
b
Double-blind continuation in selected acute-phase [x weeks] responders.
continued their ascribed treatment, double-blind, for 40 weeks. The

patients maintained their improvements as long as they remained on
active sertraline. Side effects improved over time, and compliance was
good – only 13% of patients on sertraline dropped out of treatment pre-
maturely during the extension phase. The 59 patients who completed this
study were followed up for a second year on open-label sertraline,
whereupon they showed additional clinical improvements.37
These results suggest treatment continues to be effective in the longer
term.
How long should treatment continue?
Most patients are anxious to know how long they need to take their med-
ication for. One way of tackling this question is to explore whether long-
term continuation of pharmacotherapy provides ongoing protection
against relapse. A particularly promising technique involves taking
patients who have responded to the active drug and comparing their
relapse rates following randomization to either continuous treatment or
drug discontinuation.
The interpretation of discontinuation studies is not always straightfor-
ward. The lack of agreed criteria for defining a relapse of OCD makes
comparisons between the studies difficult. In addition, the studies cannot
control against ‘withdrawal’ effects resulting from the abrupt discontinua-
tion of the medication. Withdrawal effects are related to the pharmacolog-
ical properties of the treatment agent, and are believed to complicate
clomipramine and paroxetine rather more than fluoxetine.42 They can be
difficult to distinguish from early signs of the re-emergence of OCD.
A series of controlled studies has shown that discontinuation of active
treatment is associated with a significantly greater likelihood of sympto-
matic relapse (Table 9.6), irrespective of the duration of the treatment (up
Table 9.6 Relapse prevention in OCD: double-blind discontinuation studies.
Study Drug Duration of prior Number in Follow-up after Outcome of
drug treatment study discontinuation discontinuation
(weeks)
Yaryura-Tobias et al (1976)43 Clomipramine 4 or 6 wk 13 1 Worsening of OCD

Flament et al (1985)44 Clomipramine 5 wk 19a 5 Worsening of OCD
Pato et al (1988)45 Clomipramine 5–27 mo 18 7 94.4% relapsed
Leonard et al (1988)46 Clomipramine 17 mo 21b 5 89% relapsed
Dunbar et al (1995)47 Paroxetine 9 mo 104c 36 58.8% relapsed
Romano et al (1998)48 Fluoxetine 20 wk 71c 52 32% relapsed
Robinson et al (1999)49 Sertraline 52 wk 121c 28 35.4% relapsed
a
In children.
b
In children and adolescents.
c
Survival analysis performed.
to 2 years).45 For most compounds, symptoms emerged within only a few

weeks of stopping medication. The earlier clomipramine discontinuation
studies showed higher relapse rates, possibly related to stronger with-
drawal effects. In the fluoxetine study the relapse rates were lower over-
all, and benefits of ongoing treatment were seen only in the group
receiving the 60 mg fixed dose. The study by Dunbar et al showed a con-
vincing advantage for a further 6 months of paroxetine treatment in
patients who had already responded well to 9 months of open-label treat-
ment.47 The study by Robinson et al, which has not yet been published in
full, looked at patients who had responded to a year’s treatment with ser-
traline. Twenty-eight weeks after randomization, 12% of patients continu-
ing on sertraline had relapsed, compared with over 35% on placebo.49
Quality-of-life scores continued to improve in the patients continuing their
sertraline, and deteriorated in the group switched to placebo.
Altogether, the data suggest that medication confers protection against
relapse for as long as it is continued. We may conclude that treatment
should be continued for unlimited periods. Discontinuation, if necessary,
should be gradual to minimize withdrawal effects, and patients should be
warned to look out for signs of emerging illness, whereupon reinstate-
ment of the drug may achieve the same level of improvement, although
this cannot be guaranteed.50
What is the best dose for long-term treatment?
There is little evidence to support dose reduction in the longer term, apart
from one small study in which lowering the dose of clomipramine and flu-
voxamine did not appear to increase the rates of relapse.51 In the study
by Romano et al,48 the 60 mg daily dose of fluoxetine appeared the most
effective over a 24-week extension phase. On the limited data currently
available, most experts recommend continuing treatment at the effective
dose, and the adage ‘the dose that gets you well, keeps you well’ prob-
ably applies.
Other drugs in OCD
Although SRIs are impressively effective treatments for OCD, a substan-

tial minority of cases, estimated at up to 30%, do not respond well. Atten-
tion has turned, therefore, to the investigation of alternative agents. So
far, there is little evidence supporting the role of other forms of medica-
tion in OCD. A small preliminary analysis suggested that mianserin might
be effective, but the definitive results were never published.52 One small
placebo-controlled study found promising results with clonazepam,53
another with L-tryptophan.54 The finding of no difference between
phenelzine and clomipamine, in an underpowered study that lacked a

placebo,55 was contradicted by the negative placebo-controlled
phenelzine-trial by Jenike et al.2 Clorgyline has also been shown to be
less effective than clomipramine,56 implying that there is no role for
monoamine oxidase inhibitors in OCD. The results for buspirone have
been similarly unconvincing.
Conclusion
Treatment with serotonin reuptake inhibitors effects a slow, gradual
improvement in OCD for the majority of patients. The selective SRIs are
better tolerated than clomipramine. Treatment needs to be long term, and
doses should be titrated upwards to achieve optimal results. The
response to medication can be summarized as follows:
• Early onset of response may be hard to detect.
• Slow, gradual improvements take place over weeks and months.
• Comprehensive improvement in obsessions, compulsions and mood
is observed.
• Effects are sustained as long as treatment is continued.
• Long-term treatment protects against relapse.
• Inadequate response occurs in a significant minority of cases.
References
1 Goodman W, Price L, Delgado P obsessive compulsive disorder,
et al, Specificity of serotonin reup- Arch Gen Psychiatry (1994) 51:
take inhibitors in the treatment of 302–8.
obsessive compulsive disorder: 5 McDougle CJ, Epperson CN, Pel-
comparison of fluoxamine and ton GH et al, A double-blind,
desipramine, Arch Gen Psychia- placebo-controlled study of
try (1990) 47:577–85. risperidone addition in serotonin
2 Jenike MA, Baer L, Minichiello WE reuptake inhibitor-refractory
et al, Placebo-controlled trial of obsessive compulsive disorder,
fluoxetine and phenelzine for Arch Gen Psychiatry (2000)
obsessive-compulsive disorder, 57(8):794–801.
American Journal of Psychiatry, 6 Mundo E, Guglielmo E, Bellodi L,
(1997) 154:1261–4. Effect of adjuvant pindolol on the
3 Zohar J, Chopra M, Sasson Y et antiobsessional response to flu-
al, Psychopharmacology of voxamine: a double-blind,
obsessive compulsive disorder? placebo-controlled study, Int Clin
World J Biol Psychiatry (2000) Psychopharmacol (1998) 13(5):
1(2):92–100. 219–24.
4 McDougle CJ, Goodman WK, 7 Dannon PN, Sasson Y,
Leckman J et al, Haloperidol Hirschmann S et al, Pindolol aug-
addition in fluvoxamine-refractory mentation in treatment resistant
obsessive compulsive disorder: a chopharmacol (1996) 6(2):

double-blind placebo-controlled 111–18.
trial, Eur Neuropsychopharmacol 17 Smeraldi E, Ergovesi S, Bianchi I
(2000) 10(3):165–9. et al, Fluvoxamine versus
8 Fineberg NA, Roberts A, Mont- clomipramine treatment in obses-
gomery SA et al, Brain 5-HT func- sive compulsive disorder: a pre-
tion in obsessive-compulsive liminary study, New Trends Exper
disorder. Prolactin responses to Clin Psychiatry (1992) 8(2):63–5.
D-fenfluramine, Br J Psychiatry
18 Freeman CPL, Trimble MR,
(1997) 171:280–2. Deakin JFW et al, Fluvoxamine
9 Fernandez CE, Lopez-Ibor JJ, versus clomipramine in the treat-
Monochlorimipramine in the treatment of obsessive compulsive
ment of psychiatric patients resis- disorder. A multicentre, ran-
tant to other therapies, Actas domised, double-blind parallel
Luso Esp Neurol Psiquiatr Cienc group comparison, J Clin Psychi-
Afines (1967) 26:119–47. atry (1994) 55(7):301–5.
10 Reynghe De Voxrie GV, Anafranil 19 Koran LM, McElroy SL, Davidson
(G34586) in obsessive neurosis, JRT et al, Fluvoxamine versus
Acta Neurol Belg (1968) 68: clomipramine for obsessive com-
787–92. pulsive disorder: a double-blind
11 Montgomery SA, Clomipramine in comparison, J Clin Psychophar-
obsessional neurosis; a placebo- macol (1996) 16(2):121–9.
controlled trial, Pharmacol Med 20 Milanfranchi A, Ravagli S, Lensi P
(1980) 1:189–92. et al, A double-blind study of flu-
12 De Veaugh-Geiss J, Landau P, voxamine and clomipramine in
Katz R, Treatment of obsessive the treatment of obsessive-
compulsive disorder with compulsive disorder. Int Clin Psy-
clomipramine, Psychiatry Annals chopharmacol (1997) 12:131–6.
(1989) 19:97–101. 21 Rouillon F, A double-blind com-
13 Goodman WK, Price LH, Ras- parison of fluvoxamine and
mussen SA et al, The Yale-Brown clomipramine in OCD, Eur
Obsessive-Compulsive Scale I: Neuropsychopharmacol (1998)
development, use, and reliability, 8(2):S260–1.
Arch Gen Psychiatry (1984) 22 Zohar J, Judge R, Paroxetine ver-
46:1006–11. sus clomipramine in the treatment
14 Piccinelli M, Pini S, Bellantuono C of obsessive compulsive disor-
et al, Efficacy of drug treatment in der. Br J Psychiatry (1996) 169:
obsessive compulsive disorder, 468–74.
Br J Psychiatry (1995) 166: 23 Bisserbe JC, Lane RM, Flament
424–43. MF et al, A double-blind compari-
15 Piggott TA, Pato MT, Bernstein SE son of sertraline and clomipramine
et al, Controlled comparison of in outpatients with obsessive com-
clomipramine and fluoxetine in pulsive disorder, Eur Psychiatry
the treatment of obsessive com- (1997) 153:1450–4.
pulsive disorder, Arch Gen Psy- 24 Pidrman V, Tuma I, Citalopram
chiatry (1990) 144:1543–8. versus clomipramine in double-
16 Lopez-Ibor JJ, Saiz J, Cottraux J blind therapy of obsessive com-
et al, Double-blind comparison of pulsive disorder, Abstracts 11th
fluoxetine versus clomipramine in Congress European College of
the treatment of obsessive com- Neuropsychopharmacology, Oct
pulsive disorder, Eur Neuropsy- 31–Nov 4, Paris, 1998.
25 Montgomery SA, Fineberg N, parison of three dosages of ser-

Montgomery DB, The efficacy of traline and placebo in outpatients
serotonergic drugs in OCD-power with obsessive compulsive disor-
calculations compared with der, Arch Gen Psychiatry (1995)
placebo. In: Montgomery SA, 52:289–95.
Goodman WK, Goeting N, eds, 33 Wheadon D, Bushnell W, Steiner
Current Approaches: Obsessive M, A fixed dose comparison of
Compulsive Disorder (Ashford 20, 40 or 60 mg paroxetine to
Duphar: Southampton, 1990) placebo in the treatment of
54–63. obsessive compulsive disorder.
26 Hoehn-Saric R, Harrison W, Clary Poster presented at the Annual
C, Obsessive compulsive disor- Meeting of the American College
der with comorbid major depres- of Neuropsychopharmacology,
sion: a comparison of sertraline Honolulu, Hawaii (1993).
and desipramine treatment. 34 Montgomery SA, Citalopram treat-
Poster presented at 10th ECNP, ment of obsessive compulsive
Vienna, Austria. disorder: results from a double-
27 Kejsers G, Hooddiun C, Schaap blind, placebo-controlled trial.
CP, Predictors of treatment out- Poster presented at the 37th
come in the behavioural treatment Annual Meeting of the American
of obsessive compulsive disor- College of Neuropsychopharma-
der, Br J Psychiatry (1994) 165: cology, Las Croaloas, Puerto
781–6. Rico, December 1998.
28 Hohagen F, Winkelmann G, 35 Wood A, Tollefson GD, Burkitt
Rasche-Rauchle H et al, Combi- M. Pharmacotherapy of obsessive
nation of behaviour therapy with compulsive disorder – experience
fluvoxamine in comparison with with fluoxetine, Int Clin Psy-
behaviour therapy and placebo. chopharmacol (1993) 8:301–6.
Results of a multicentre study, Br 36 Stahl S, Psychopharmacology of
J Psychiatry (1998) 173:71–8. Antidepressants (Martin Dunitz:
29 Fineberg NA, Roberts A, Mont- London, 1997) 56–8.
gomery SA, Are higher doses 37 Rasmussen S, Hackett E, DuBoff
more effective in OCD? Eur Neu- E et al, A 2-year study of sertra-
ropsychopharmacol (1994) 4(3): line in the treatment of obsessive-
264–5. compulsive disorder, Int Clin
30 Montgomery SA, McIntyre A, Psychopharmacol (1997) 12:
Osterheider M et al, A double- 309–16.
blind placebo-controlled study of 38 Wagner KD, March J, Landau P
fluoxetine inpatients with et al, Safety and efficacy of ser-
DSM-III-R obsessive compulsive traline in long-term paediatric
disorder. The Lilly European OCD OCD treatment: a multicentre
Study Group, Eur Neuropsy- study. Presented at the 39th
chopharmacol (1993) 3:143–52. Annual Meeting of the New Clini-
31 Tollerfson G, Rampey A, Potvin J cal Drug Evaluation Unit, Boca
et al, A multicentive investigation Raton, Fla, 1999.
of fixed-dose fluoxetine in the 39 Cottraux J, Mollard E, Bouvard M
treatment of obsessive compul- et al, A controlled study of fluvox-
sive disorder, Archives of General amine and exposure in obsessive
Psychiatry (1994) 51:559–67. compulsive disorders, Int Clin
32 Greist J, Chouinard G, Duboff E Psychopharmacol (1990) 5:
et al, Double-blind parallel com- 17–30.
40 Katz RJ, De Veaugh-Geiss J, Lan- disorder following acute

dau P, Clomipramine in response: a comparison of fluoxe-
obsessive-compulsive disorder, tine versus placebo, Eur Neu-
Biol Psychiatry (1990) 18:401–4. ropsychopharmacol (1998)
41 Greist J, Jefferson J, Kobak K et 8(suppl. 2):261.
al, A one year double blind 49 Robinson D, Kiev A, Hackett E et
placebo-controlled fixed dose al, Sertraline in long-term OCD
study of sertraline in the treatment treatment: results of a multicentre
of obsessive compulsive disor- study. Presented at the XI World
der, International Clinical Psy- Congress of Psychiatry, Ham-
chopharmacology (1995) 10: burg, 1999.
57–65. 50 Ravizza L, Maina G, Bogetto F et
42 Sechter D, Lane R, Continuation al, Long-term treatment of obses-
therapy with selective serotonin sive compulsive disorder, CNS
reuptake inhibitors, J Ser Res Drugs (1998) 10(4):247–55.
(1997) 4:65–113. 51 Mundo E, Bareggi SR, Pirola R et
43 Yaryura-Tobias JA, Neziroglu F, al, Long-term pharmacotherapy
Bergman L, Clomipramine for of obsessive compulsive disor-
obsessive-compulsive neurosis: der: a double-blind controlled
an organic approach, Curr Thera- study, J Clin Psychopharmacol
peutics Res (1976) 20:541–8. (1997) 17:4–10.
44 Flament MF, Rapoport JL, Berg 52 Jaskari MO, Observations on
CJ, Clomipramine treatment of mianserin in the treatment of
childhood OCD: a double-blind obsessive neuroses, Curr Med
controlled study, Arch Gen Psy- Res Opin 6:128–31.
chiatry (1985) 42:977–83. 53 Hewlett WA, Vinogradov S, Agras
45 Pato MT, Zohar-Kadouch R, WS, Clomipramine, clonazepam
Zohar J, Return of symptoms after and clonidine treatment of
discontinuation of clomipramine obsessive-compulsive disorder, J
in patients with obsessive com- Clin Psychopharmacol (1992)
pulsive disorder, Am J Psychiatry 12:420–30.
(1988) 145:211–14. 54 Montgomery SA, Fineberg NA,
46 Leonard H, Swedo S, Rapoport J Montgomery DB et al, L-trypto-
et al, Treatment of childhood phan in obsessive compulsive
obsessive compulsive disorder disorder – a placebo-controlled
with clomipramine and study, Eur Neuropsychopharma-
desmethylimipramine: a double col (1992) 2(suppl. 2):384.
blind crossover comparison, Psy- 55 Vallejo J, Olivares J, Marcos TI
chopharmacol Bull (1988) 24(1): et al, Clomipramine versus
93–5. phenelzine in obsessive compul-
47 Dunbar G, Steiner M, Bushnell sive disorder. A controlled clinical
WD et al, Long-term treatment trial, Br J Psychiatry (1992) 161:
and prevention of relapse of 665–70.
obsessive compulsive disorder 56 Insel TR, Murphy DL, Cohen RM
with paroxetine, Eur Neuropsy- et al, Obsessive-compulsive dis-
chopharmacol (1995) 5:372. order – a double-blind trial of
48 Romano S, Goodman WK, clomipramine and clorgyline,
Tamura T et al, Long-term treat- Arch Gen Psychiatry (1983) 40:
ment of obsessive-compulsive 605–12.
10
Psychotherapy in OCD
Andreas Broocks and Fritz Hohagen
For decades, obsessive compulsive disorder (OCD) was considered to

be a fascinating but treatment-refractory mental condition. Conventional
pharmacological approaches as well as psychodynamic therapy failed to
achieve satisfactory improvements in obsessive compulsive symptoma-
tology.1 The first major advances in the treatment of OCD came from two
different approaches. Clomipramine, which differs from other tricyclic
antidepressants by its potent inhibition of serotonin reuptake, proved to
exert specific antiobsessional effects. At the same time, the introduction
of special cognitive-behavioral techniques began to improve the progno-
sis of OCD continuously. In subsequent years, many studies have shown
that behavior therapy, especially exposure with response prevention, and
selective serotonin reuptake inhibitors (SSRIs) reduce obsessive compul-
sive symptoms significantly.2–6 Nevertheless, several questions remain
open for discussion and further research. This article reviews different
psychotherapeutic approaches in the treatment of OCD such as expo-
sure therapy, cognitive techniques, multimodal behavioral therapy, and
group therapy. In addition, the question of combined behavioral and
pharmacotherapeutic treatment is discussed, and suggestions for further
research are given.
Early treatment approaches
The first psychological interventions in the treatment of OCD were expo-

sure techniques such as systematic desensitization and reinforcement
procedures including aversion. Unfortunately, these therapies were not
very effective.7,8 The first approach, which in fact resembled current
forms of imaginative and in vivo exposure, was the so-called paradoxical
intention: in vivo confrontation with symptom-inducing stimuli was cou-
pled with instructions to elaborate the obsessional material. These early
approaches helped to advance the development of the modern exposure
and response prevention technique which has proved to be highly
119
effective. Early cognitive interventions such as thought-stopping were

only examined in case reports or in uncontrolled studies without any
long-term documentation of therapy success.
Exposure and response prevention
Meyer’s case report is, to our knowledge, the first description of a suc-
cessful behavioral treatment characterized by prolonged exposure to
obsessional cues and – at the same time – strict prevention of
responses.9 This finding was corroborated in two further open studies
which additionally demonstrated a surprisingly low relapse rate at 5-year
follow-up. Meanwhile, exposure/response prevention has been com-
pared with various control treatments including relaxation, anxiety man-
agement training, and pill placebo,10 leading to further evidence for the
efficacy of this procedure. Current exposure/response prevention pro-
grams usually combine in vivo exercises of exposure to feared stimuli
with imaginative exposure.11 Repeated prolonged exposure leads to a
psychophysiological habituation process, which also affects irrational
beliefs held by the patient. Most therapists use gradual exposure which
seems to be associated with better acceptance by the patients. Flooding
has not been observed to be better than a gradual approach.7 Because
motivation is crucial for a successful therapy, we prefer a hierarchy-
oriented increase of exposure intensity. We also recommend the addition
of imaginal exposure to in vivo exposure/response prevention, which has
shown to be advantageous in clinical studies.11 In some patients, in vivo
exposure exercises are not possible, because their obsessional fears
consist of unrealistic disastrous events; therefore, imaginal exposure is a
key element of treatment in these patients. It is crucial that the duration of
the exposure exercise continues at least until the patient experiences a
decrease of the induced distress. The time needed to achieve sufficient
habituation varies from patient to patient and will often require 90 minutes
or more.12 Some researchers have reported excellent results with a high-
frequency treatment involving daily sessions, but favorable outcomes
have also been gained with a session frequency of once per week.13,14 In
an inpatient treatment program patients with severe symptoms and those
who exhibited considerable resistance to exposure were observed to
benefit from a more intensive regimen.
Although there is only sparse evidence from clinical studies that
therapist-assisted exposure is more potent than self-exposure, clinical
experience suggests that patients will expose themselves to feared situa-
tions more readily in the presence of a therapist. In addition, patients are
asked to conduct self-directed exposure exercises between these
guided sessions. Importantly, patients should not be stopped from per-
forming their rituals by physical prevention as described in the early stud-
Psychotherapy 121
ies of Meyer and co-workers. Instead, the therapist will give instructions
and encouragement to support the patient’s own decision not to perform
compulsive behaviors.15 Therapists should also be alert in order to detect
and restrain covert neutralizing thoughts.16 Alternative activities have to
be practised for situations characterized by strong urges to indulge in
obsessive compulsive behavior. In general, it will be helpful to find a
friend or a family member who is able to provide co-therapeutic func-
tions; this person must be trained in ways of supporting the patient
between sessions in order to achieve adequate exposure. High emo-
tional arousal is usually experienced as anxiety. However, some patients
will describe their emotions during exposure as anger, aggression or
depression. Irrespective of these emotional variations, the patient has the
task of describing precisely the experienced emotions and the accompa-
nying cognitions. This description is the basis of the cognitive restructur-
ing which most therapists view as an important component of successful
exposure.
Most studies that have examined the efficacy of exposure therapy for
OCD also included response prevention techniques, thus confounding
the effects of the single procedures. To separate these effects, Foa et al
randomly assigned patients with compulsive washing to treatment by
exposure only, response prevention only, or their combination (expo-
sure/response prevention).17 Results showed that the combined treat-
ment was superior to the single treatments on most symptom measures.17
In summary, despite promising results from new cognitive approaches,
exposure/response prevention still has the key role in the treatment of
OCD. Foa and Kozak reviewed 12 outcome studies using
exposure/response prevention (n ⫽ 330), and found that an average of
83% of treatment completers were classified as responders immediately
after treatment.18 In 16 studies reporting long-term outcome (n ⫽ 376)
76% of the patients were responders; the mean follow-up interval in the
latter group of studies was 29 months. Several meta-analytic studies
have detected large effect sizes for exposure/response prevention with
OCD in adults (>1.0).18
Cognitive approaches in the treatment of OCD
In recent years, cognitive approaches have been proposed for the treat-
ment of OCD, especially obsessional ruminations.19,20 Cognitive therapy
is thought to work by altering both strongly held beliefs associated with
OCD symptoms and interpretations of intrusive mental experiences. Fol-
lowing the work of Rachman and Hodgson,21 Salkovskis and co-workers
distinguished between anxiety-producing thoughts and secondary neu-
tralizing thoughts.16,22 They proposed exposure techniques by thought
evocation or listening to a ‘loop tape’ of the anxiety-provoking thought in
the patient’s own voice followed by response prevention (i.e. no overt or

covert neutralizing or avoidance behavior). Additionally, a cognitive
model of OCD was developed based on the general model as applied to
anxiety disorders. The cognitive-behavioral theory of OCD proposes that
obsessional thoughts and normal intrusive thoughts do not in themselves
differ.23,24 The difference lies in how the obsessional patient interprets the
occurrence and/or content of the intrusions. According to the cognitive
hypothesis, obsessional problems occur when intrusive cognitions are
interpreted as an indication that the person may be, may have been, or
may come to be responsible for harm or its prevention.20,25 According to
Salkovskis, this specific interpretation of the occurrence and content of
intrusive thoughts – responsibility for harm to oneself or other people –
links intrusions with both the discomfort experienced and the neutralizing
(compulsive) behaviors whether overt or covert. Neutralizing and avoid-
ance behavior, a tendency to overfocus attention on the contents of one’s
own mind, and negative mood can all interact, in the context of the gen-
eral cognitive theory, to maintain the negative belief concerning responsi-
bility.22 Cognitive therapy seeks to change responsibility beliefs and
appraisals and thereby to reduce distress and eliminate neutralizing
responses, which usually occur as covert neutralizing (mental) rituals. In
contrast to the fears of patients suffering from panic disorder or social
phobia, the catastrophes feared by OCD patients usually lie further in the
future; therefore, disconfirmation is much less useful as a strategy. Much
depends on a process in which the patient and the therapist develop a
non-threatening explanation of the problem. This alternative account
reminds the patient that there are at least two possible explanations for
the problem: it is possible that there really is a danger of causing harm or
not preventing negative incidents; on the other hand there might only be
excessive worry about possible harm leading to constant anxiety and
concern.
Many obsessional patients try to suppress their anxiety-laden thoughts.
Some of these patients believe that they are not overwhelmed by their
obsessional thoughts only because of their constant resistance or
because of distraction techniques. In such a situation cognitive therapists
would introduce behavioral experiments. In this example, the patient
would be asked to keep a diary record of the frequency and intensity of
the obsessional thought under two opposite conditions: on the first day
every attempt should be made to distract attention from the thought, and
on the other day all thoughts should be allowed to come and go without
suppressing them. It is also important to help patients to identify and to
modify underlying general assumptions which might represent the roots
of the more overt dysfunctional thoughts. As in other anxiety disorders,
the general style of therapy is that of guided discovery. Further details of
the cognitive treatment of obsessions including the use of loop tapes are
described by Salkovskis et al.22
Psychotherapy 123
A number of published case reports in case series provide evidence

for the clinical effectiveness of the cognitive approach.19,26 More recently,
Freeston reported the results of a controlled trial in which cognitive-
behavioral therapy (CBT) was significantly superior in comparison with a
waiting-list control group.27 Treatment effects persisted at 6-month follow-
up, Schwartz has proposed a cognitive-biobehavioral self-treatment for
OCD.28 This integrates the results of neuroimaging research into the cog-
nitive approach based on the literature on the behavioral neurobiology of
the basal ganglia. It is founded on the assumption that OCD symptoms
are related to a malfunction in cortical circuit activation in the fronto-
striatal system; therefore, activation of an alternative circuit through the
focused performance of a familiar alternative behavior might over time
ameliorate the discomfort related to the faulty brain mechanism. In a four-
step process, the OCD patient learns to identify his or her obsessions
and compulsions, to label them as such (‘It’s not me, it is my OCD’), and
to attribute them to abnormal activity of the frontostriatal system (‘relabel,
reattribute, refocus, revalue’). While ‘working around OCD symptoms’,
patients learn new adaptive responses to intrusive OCD thoughts and
urges. They are tutored to become increasingly aware of avoidant behav-
iors and to use treatment techniques to perform previously avoided
behaviors. As a result of this systematic change in behavioral responses
to OCD symptoms, patients come to revalue the intrusive thoughts and
urges as much less important and noteworthy. Fear and anxiety associ-
ated with OCD symptoms gradually fade.28
Since these cognitive approaches have to varying extents included
exposure techniques, the question remains whether pure cognitive ther-
apy is equivalent to exposure therapy in the treatment of OCD, or
whether the addition of cognitive techniques can improve the results of
exposure therapy. The efficacy of rational emotive therapy (RET), a cog-
nitive therapy program that focuses on irrational beliefs, has been exam-
ined by Emmelkamp et al.29 Patients were randomly assigned to RET or
to exposure/response prevention, the RET focused on irrational thoughts
that caused negative feelings and the modification of these thoughts by
cognitive techniques in order to reduce anxiety and the urge to perform
rituals. At the end of the treatment, both groups showed comparable
improvements. Van Oppen et al compared the efficacy of self-controlled
exposure/response prevention and a cognitive intervention developed to
correct specific cognitive distortions. At the end of the treatment period,
OCD symptom reductions of 20% were observed for cognitive therapy
and 23% for exposure/response prevention.30 This study, however, com-
pared cognitive techniques with self-help exposure, the least effective
version of exposure; therapist-guided exposure, which may be more effi-
cacious, was not included. James and Blackburn presented a meta-
analysis of 15 published studies of cognitive therapy in OCD. They did
not find a significant additional effect ascribable to cognitive therapy.31
Most studies comparing exposure/response prevention to variants of

cognitive therapy are limited by the fact that the behavioral exercises are
not applied in the intensity and/or frequency necessary to achieve opti-
mal effects. Cottraux and co-workers compared cognitive therapy with
intensive behavioral therapy in 64 outpatients in a multicenter study.32
Group 1 received twenty 1-hour sessions of cognitive therapy over 16
weeks. Group 2 received a 4-week intensive treatment with two sessions
of 2 hours’ duration per week and a 12-week maintenance phase with
booster sessions. The behavioral therapy program included imaginal and
in vivo exposure with response prevention during the sessions, and
homework. Preliminary data indicate that there were no significant differ-
ences between the two treatment groups. This study suggests that cogni-
tive therapy is as effective as exposure therapy. However, recent
meta-analytic findings suggest that cognitive therapies which also use
‘behavioral experiments’ are superior to pure cognitive approaches.33 On
the other hand, ‘pure’ exposure/response prevention is a theoretical con-
struct, because dysfunctional thinking and irrational beliefs are usually
discussed during exposure sessions. It is likely that one of the central
mechanisms explaining the efficacy of exposure is the correction of false
beliefs. Accordingly, cognitive therapy will always include behavioral
experiments as an important tool for cognitive restructuring.7 Therefore, in
clinical practice, it seems justified to use the term ‘cognitive-behavioral
therapy’ (CBT) for all of these approaches.
Multimodal cognitive-behavioral therapy

Unfortunately, at least 25% of OCD patients do not comply with cognitive
behavioral therapy.34 In addition to those who drop out, 20–30% do not
respond sufficiently. Thus, a considerable number of patients are in need
of further support.35 Interestingly, biographies of OCD patients show that
at least half of them suffer from anxiety problems, low self-esteem, social
deficits, and more or less latent aggression resulting in marked problems
in daily life conduct.36 To treat these patients more effectively, there is an
increasing interest in multimodal CBT programs. This treatment approach
analyzes and treats early social deficits, reduced tolerance for intensive
emotions, and reduced emotional awareness. It deals with deficits in
problem-solving and self-initiated alternative behaviors as well as inter-
personal problems. Principally, it also uses symptom-directed interven-
tions, i.e. cognitive techniques and exposure with response prevention.
Prior to developing the first treatment plan in collaboration with the
patient, it is helpful to check whether the following assessments have
already been made from the information gained in the first few sessions
with the patient: internal or external motivation for treatment and change,
other interpersonal or financial problems, biographical analysis in order
Psychotherapy 125
to identify factors that have triggered or maintained the OCD symptoma-

tology, and functional analysis of compulsive or obsessional symptoms. It
is also important to discuss the consequences for daily life when most of
the OCD symptoms have disappeared. This rather complex analysis may
lead to quite different treatment plans: in ‘uncomplicated’ cases,
symptom-directed treatment might be the only therapeutic intervention;
other patients will additionally require techniques in order to reduce trig-
gering and maintaining factors. More severely affected patients might
need the full armoury of the multimodal approach: symptom-directed
cognitive and exposure techniques, deficit-directed procedures such as
social skills training, problem-solving skills, self-induced alternative
behaviors, and interventions aiming to increase motivation for change.
This approach also tries to reduce perfectionism, striving for absolute
security and predictability of future events. In severe cases, complex
combinations of multimodal interventions are often needed, including
marital or family interventions as well as individual or group treatments. In
addition to symptom reduction, in multimodal CBT patients are trained to
improve their awareness of unresolved problems, their behavioural
deficits, and their personal resources and abilities that can be activated
for significant progress in daily life conduct.
Multimodal CBT has been shown to be effective, with very low drop-out
rates in severely ill inpatients and outpatients.37,38 Furthermore, its long-
term efficacy has been demonstrated in follow-up studies in unselected
patients.38 Whether multimodal behavioral therapy is superior to exposure
therapy alone, and whether it is appropriate to treat refusers, drop-outs,
and non-responders to conventional exposure therapy with response
prevention, are still open questions. Furthermore, the impact of different
health-care systems on patient selection has to be taken into considera-
tion. While most of the studies carried out in the USA involved motivated
outpatients, European studies have been carried out with patients
referred to psychiatry departments;37–39 these patients often have low
motivation to change behavior. A health-care system that covers all treat-
ment costs including repeated hospital treatments of variable length
might also impair the motivation to change obsessive compulsive behav-
ior in some patients. Thus, increasing motivation for behavioral change is
an important part of multimodal behavioral therapy; it may make this
approach useful for OCD patients who drop out or refuse to undergo
exposure therapy alone.
Group therapy
The different variations of CBT discussed so far have well-established
efficacy for the treatment of OCD. However, the lack of experienced
therapists and the cost of multiple individual treatment sessions often
preclude its use and raise the question of whether these interventions
could be applied successfully in the form of group therapy. Evidence for
the clinical efficacy of group therapy derives from several studies.40–42 It
was reported that group therapy reduced distress caused by OCD symp-
toms, general depression, and anxiety by the end of treatment, although
patients receiving individual behavioral therapy demonstrated faster
reductions in OCD symptom severity.41,42 A 6-month follow-up showed
that treated participants were able to maintain their gains. Another recent
study added more evidence for the clinical efficacy of group therapy
treatment.43 However, patients in both studies were moderately ill and the
decrease in Yale–Brown Obsessive Compulsive Scale (Y–BOCS, see
Appendix 1, p. 183) values was somewhat lower after 12 weeks of treatment
compared with individual treatment in more severely ill OCD patients.44,45
Thus, further research is needed to investigate whether group therapy is as
effective as individual therapy in the treatment of OCD patients.
Combination of CBT and medication
Only a few studies have investigated whether the combination of

pharmacotherapy with CBT is superior to CBT alone. Furthermore, few
data are available on the differential indication for pharmacotherapy,
CBT, or combined treatment. Marks et al have compared the combina-
tion of clomipramine plus exposure in vivo with clomipramine and expo-
sure separately.46 When added to exposure therapy, clomipramine
treatment improved some measures of rituals and depression signifi-
cantly more than placebo medication during 7 weeks of self-exposure
instructions. This effect was transient and disappeared as drug treatment
and exposure were continued for a further 15 weeks. The authors con-
cluded that clomipramine had a limited adjuvant role.46 The results from
another study indicated that although imipramine improved depressive
symptoms in depressed patients with OCD, it did not affect obsessive
compulsive symptoms and did not potentiate the antiobsessional effects
of behavior therapy.44 Cottraux et al compared exposure therapy, fluvox-
amine, and combination treatment in patients with OCD.32 They reported
a drug effect on rituals at week 8 and on depression at week 24. Both
effects disappeared at week 48 and at the 18-month follow-up; patients
as a whole remained improved with no between-group differences. The
sequential combination of fluvoxamine with cognitive therapy or exposure
in vivo with response prevention was not superior to either cognitive ther-
apy or exposure alone.45 Khanna and co-workers conducted a study to
evaluate the differences between treatment with fluoxetine alone versus
fluoxetine plus exposure and response prevention in 40 previously
untreated patients with OCD.47 They concluded that exposure and
response prevention may have a limited role in the initial treatment of
Psychotherapy 127
OCD. Hohagen et al investigated whether the combination of multimodal

CBT with fluvoxamine is superior to CBT and placebo in the acute treat-
ment of severely ill inpatients with OCD.37 This study also looked at
whether the pharmacologic treatment of secondary depression improves
the treatment outcome of obsessive and compulsive symptoms. Both
groups showed a highly significant symptom reduction after treatment.
There were no significant differences between the groups concerning
compulsions. Obsessions were significantly more reduced in the fluvox-
amine–CBT group than in the placebo–CBT group. Furthermore, the fluvox-
amine–CBT group showed a significantly higher response rate (87.5%
versus 60%) according to the previously defined response criterion (>35%
symptom reduction in the Y–BOCS scores, see Appendix 1, p. 183).
Severely depressed patients with OCD receiving CBT plus fluvoxamine
had a significantly better treatment outcome (Y–BOCS scores, see
Appendix 1, p. 183) than severely depressed OCD patients receiving
CBT plus placebo. The authors concluded that differential analysis of the
clinical syndrome of OCD suggests different treatment strategies. When
compulsions dominate the clinical picture, CBT alone seems to be suffi-
cient to treat patients effectively. If the patients suffer predominantly from
obsessions, then addition of SSRI therapy to CBT may improve treatment
outcome. If the patients suffer from secondary depression, SSRIs seem
to enhance the treatment outcome of OCD significantly and should be
added to CBT. Furthermore, from the literature it can be concluded that
SSRIs should be combined with a neuroleptic, if a tic disorder is present
in addition to OCD.48 Unfortunately, there is a high relapse rate of around
70–80% after discontinuation of medication.49,50 A clinical study is in
progress to find out to what extent this relapse rate can be reduced by
concomitant CBT.
Predictors of treatment outcome
The identification of prognostic variables associated with treatment failure

or success could lead to modified treatment programs. Most data on pre-
dictors of treatment outcome are derived from psychopharmacologic
studies.51 Studies investigating prognostic factors for CBT have identified
the following negative predictors: high OCD severity at the beginning of
treatment;35,52 severe depression;8,35,37,53 overvalued or fixed obsessive
ideation;54 unemployment; 55,56 comorbidity with personality disorder;57–59
and lack of motivation for treatment.52 The presence of hoarding obses-
sions and compulsions was also associated with poorer response to sero-
tonin reuptake inhibitors.60 Certain personality disorders, especially
schizotypal and borderline conditions, have also been found related to
poor response to serotonin reuptake inhibitors.29,57 A 2-year follow-up study
after multimodal inpatient treatment showed that treatment compliance was
a predictor for long-term outcome. Patients who discontinued exposure

therapy were more likely to be classified as non-responders (response
defined as 35% symptom reduction in the Y–BOCS (see Appendix 1);
F Hohagen et al, unpublished data). The importance of exposure therapy
was also underlined by a study by De Araujo and co-workers.15 The best
predictor of good outcome at the end of treatment (week 9) and of follow-
up (week 32) was early compliance in doing exposure homework within a
week of starting treatment. These studies have been done in adult OCD
patients. Predictors of CBT outcome have not been reported for child-
hood OCD.
Future questions
Although the percentage of patients who refuse to participate in behav-

ioral therapy is smaller in the multimodal approach when compared with
the intensive exposure/response prevention treatment programs, the
motivational background for this kind of avoidance behavior should be
examined in greater depth in order to find new ways of overcoming these
barriers to effective treatment. We also need studies in community-based
treatment facilities to find out whether the excellent results from special-
ized centers can be obtained in other settings. The efficacy, acceptance
and cost-effectiveness of short-term interventions for patients suffering
from less severe forms of OCD need further improvement. Self-directed
exposure using self-help manuals seems to be effective in a subgroup of
OCD patients. More research is required to identify patients who are able
to overcome their problems by pure self-help or manual-guided exposure
strategies. The German Society for the Treatment of Obsessive Compul-
sive Disorder supports the foundation of self-help groups all over the
country; the scientific evaluation concerning the therapeutic and health-
economic potential of these groups is still at a preliminary stage.61
Another intriguing research field is the question whether neurobiologi-
cal abnormalities associated with OCD can be modulated by effective
treatment strategies. With cognitive-behavioral treatment, significant
decreases in caudate glucose metabolism were found in treatment
responders compared with non-responders. Pretreatment metabolic cor-
relations between orbital cortex and caudate and between orbital cortex
and thalamus were found, which decreased significantly with successful
CBT.62,63 Furthermore, the percentage change in the Y–BOCS score (see
Appendix 1) was positively correlated with the percentage change in
metabolism in the left orbital cortex.63 It would be of great interest if para-
meters which (in comparison to positron emission tomography findings)
can be more easily measured in clinical settings turn out to be predictors
of treatment success or predictors of relapse at the end of a successful
treatment.
Psychotherapy 129
Conclusion
In summary, the results of existing studies suggest that cognitive-
behavioral therapy which includes exposure/response prevention and
possibly other elements from the multimodal approach represents a
treatment of choice for the majority of patients suffering from OCD. When
CBT is not available or is rejected by the patient, or is ineffective, sero-
tonergic medications are a therapeutic alternative with well-documented
efficacy. Also, when the OCD is complicated by severe depression or
when patients suffer predominantly from obsessions, pharmacotherapy is
likely to improve the outcome of CBT. It is considered to be one of the
major disadvantages of drug therapy that symptom reappearance gener-
ally occurs after tapering off the medication. However, in the authors’
experience the long-term effects of CBT, demonstrated in several follow-
up studies, also depend on the continuous practice of the newly adopted
cognitive and behavioral strategies. Recurrence of OCD symptoms is
likely when patients do not adhere to the newly adopted cognitive-
behavioral habits because of motivational problems, acute life stress or
depression. Despite all progress in treatment, OCD still is a chronic dis-
order which principally needs long-term treatment. However, it is a major
advance that new, sophisticated cognitive-behavioral treatment pro-
grams enable many OCD patients to become their own experts in over-
coming OCD-related symptoms and associated psychosocial
impairments.
References
1 Greist JH, Treatment of obsessive 5 Mundo E, Bianchi L, Bellodi L,
compulsive disorder: psychother- Efficacy of fluvoxamine, paroxe-
apies, drugs, and other somatic tine, and citalopram in the treat-
treatment, J Clin Psychiatry ment of obsessive-compulsive
(1990) 44–50; discussion 55–8. disorder: a single-blind study, J
2 Marks I, Behaviour therapy for Clin Psychopharmacol (1997)
obsessive-compulsive disorder: a 17(4):267–71.
decade of progress, Can J Psy- 6 Rosenberg DR, Stewart CM,
chiatry (1997) 42(10):1021–7. Fitzgerald KD, Tawile V, Carroll E,
3 Greist JH, Jefferson JW, Pharma- Paroxetine open-label treatment
cotherapy for obsessive- of pediatric outpatients with
compulsive disorder, Br J obsessive-compulsive disorder, J
Psychiatry (1998) (suppl. 35): Am Acad Child Adolesc Psychia-
64–70. try (1999) 38(9):1180–5.
4 Pigott TA, Seay SM, A review of 7 Minichiello WE, Baer L, Jenike MA,
the efficacy of selective serotonin Behavior therapy for the treatment
reuptake inhibitors in obsessive- of obsessive-compulsive disorder:
compulsive disorder, J Clin Psy- theory and practice, Compr Psy-
chiatry (1999) 60(2):101–6. chiatry (1988) 29(2):123–37.
8 Foa EB, Failure in treating 18 Foa EB, Kozak MJ, Psychological

obsessive-compulsives, Behav treatment for OCD. In: Mavis-
Res Ther (1979) 17(3):169–76. sakalian MR, Prien RF, eds, Long-
9 Meyer V, Modifications of expec- term Treatments of Anxiety
tations in cases of obsessional rit- Disorders (American Psychiatric
uals, Behav Res Ther (1966) Press: Washington, 1996)
4:273–80. 235–309.
10 Kozak MJ, Liebowitz MR, Foa EB, 19 Salkovskis PM, Understanding and
Cognitive behavior therapy and treating obsessive-compulsive dis-
pharmacotherapy for OCD. In: order, Behav Res Ther (1999)
Goodman WK, ed., Obsessive- S29–52.
Compulsive Disorder: Contempo- 20 Salkovskis P, Shafran R, Rach-
rary Issues in Treatment (Harper: man S, Freeston MH, Multiple
Washington, 1999). pathways to inflated responsibil-
11 Foa EB, Steketee G, Turner RM, ity beliefs in obsessional prob-
Fischer SC, Effects of imaginal lems: possible origins and
exposure to feared disasters in implications for therapy and
obsessive-compulsive checkers, research, Behav Res Ther (1999)
Behav Res Ther (1980) 37(11):1055–72.
18(5):449–55. 21 Rachman SJ, Hodgson RJ,
12 Foa EB, Chambless DL, Habitua- Obsessions and Compulsions
tion of subjective anxiety during (Prentice-Hall: Englewood Cliffs,
flooding in imagery, Behav Res 1980).
Ther (1978) 16(6):391–9. 22 Salkovskis PM, Forrester E,
13 Leonard HL, New developments Richards C, Cognitive-behavioural
in the treatment of obsessive- approach to understanding obses-
compulsive disorder, J Clin Psy- sional thinking, Br J Psychiatry
chiatry (1997) 14(39):39–45; (1998) (suppl. 35):53–63.
discussion 46–7. 23 Langlois F, Freeston MH,
14 Rapoport JL, Recent advances in Ladouceur R, Differences and
obsessive-compulsive disorder similarities between obsessive
[see comments], Neuropsycho- intrusive thoughts and worry in a
pharmacology (1991) 5(1): 1–10. non-clinical population: study 2,
15 De Araujo LA, Ito LM, Marks IM, Behav Res Ther (2000) 38(2):
Early compliance and other fac- 175–89.
tors predicting outcome of expo- 24 Langlois F, Freeston MH,
sure for obsessive-compulsive Ladouceur R, Differences and
disorder, Br J Psychiatry (1996) similarities between obsessive
169(6):747–52. intrusive thoughts and worry in a
16 Salkovskis PM, Westbrook D, non-clinical population: study 1,
Davis J, Jeavons A, Gledhill A, Behav Res Ther (2000) 38(2):
Effects of neutralizing on intrusive 157–73.
thoughts: an experiment investi- 25 Rheaume J, Freeston MH, Dugas
gating the etiology of obsessive- MJ, Letarte H, Ladouceur R, Per-
compulsive disorder, Behav Res fectionism, responsibility and
Ther (1997) 35(3):211–19. obsessive-compulsive symptoms,
17 Foa EB, Steketee G, Milby JB, Dif- Behav Res Ther (1995) 33(7):
ferential effects of exposure and 785–94.
response prevention in obsessive- 26 Roth AD, Church JA, The use of
compulsive washers, J Consult revised habituation in the treat-
Clin Psychol (1980) 48(1):71–9. ment of obsessive-compulsive
Psychotherapy 131
disorders, Br J Clin Psychol Behav Res Ther (1999) 37(8):

(1994) 3:201–4. 771–81.
27 Freeston MH, Ladouceur R, 37 Hohagen F, Winkelmann G,
Gagnon F, Cognitive-behavioural Rasche RH, Combination of
treatment of obsessive thoughts: behaviour therapy with fluvoxam-
a controlled study, J Consult Clin ine in comparison with behaviour
Psychol (1997) 65(3):405–13. therapy and placebo. Results of a
28 Schwartz JM, Brain Lock (Harper multicentre study, Br J Psychiatry
Collins: New York, 1996). (1998) (suppl. 35):71–8.
29 Emmelkamp PM, Beens H, Cogni- 38 Hand I, Out-patient, multi-modal
tive therapy with obsessive- behaviour therapy for obsessive-
compulsive disorder: a compulsive disorder, Br J Psychi-
comparative evaluation, Behav atry (1998) (suppl. 35):45–52.
Res Ther (1991) 29(3):293–300. 39 Munford PR, Hand I, Liberman
30 Van Oppen P, de Haan E, van RP, Psychosocial treatment for
Balkom AJ, Spinhoven P, Hoog- obsessive-compulsive disorder,
duin K, van Dyck R, Cognitive Psychiatry (1994) 57(2):142–52.
therapy and exposure in vivo in 40 Krone KP, Himle JA, Nesse RM, A
the treatment of obsessive com- standardized behavioral group
pulsive disorder, Behav Res Ther treatment program for obsessive-
(1995) 33(4):379–90. compulsive disorder: preliminary
31 James IA, Blackburn IM, Cognitive outcomes, Behav Res Ther (1991)
therapy with obsessive-compulsive 29(6):627–31.
disorder [see comments], Br J Psy- 41 Fals-Stewart W, Lucente S, Behav-
chiatry (1995) 166(4):444–50. ioral group therapy with obsessive-
32 Cottraux J, Mollard E, Bouvard M, compulsives: an overview, Int J
Marks I, Exposure therapy, fluvox- Group Psychother (1994) 44(1):
amine, or combination treatment 35–51.
in obsessive-compulsive disor- 42 Fals-Stewart W, Marks AP,
der: one-year followup, Psychiatry Schafer J, A comparison of
Res (1993) 49(1):63–75. behavioral group therapy and
33 Abramowitz JS, Meta-analysis of individual behavior therapy in
psychological treatments in OCD, treating obsessive-compulsive
in press, 2001. disorder [see comments], J Nerv
34 Schwartz JM, Neuroanatomical Ment Dis (1993) 181(3):189–93.
aspects of cognitive-behavioural 43 Van Noppen BI, Pato MT, Mars-
therapy response in obsessive- land R, Rasmussen SA, A time-
compulsive disorder. An evolving limited behavioral group for
perspective on brain and behav- treatment of obsessive-
iour, Br J Psychiatry (1998) compulsive disorder, J Psy-
(suppl. 35):38–44. chother Pract Res (1998) 7(4):
35 Keijsers GP, Hoogduin CA, 272–80.
Schaap CP, Predictors of treat- 44 Foa EB, Kozak MJ, Steketee GS,
ment outcome in the behavioural McCarthy PR, Treatment of
treatment of obsessive-compulsive depressive and obsessive-
disorder [see comments], Br J compulsive symptoms in OCD by
Psychiatry (1994) 165(6):781–6. imipramine and behaviour ther-
36 Ehntholt KA, Salkovskis PM, apy, Br J Clin Psychol (1992) 4:
Rimes KA, Obsessive-compulsive 279–92.
disorder, anxiety disorders, and 45 Van Balkom AJ, de Haan E, van
self-esteem: an exploratory study, Oppen P, Spinhoven P, Hoogduin
KA, van Dyck R, Cognitive and of outcome and early vs. late
behavioral therapies alone versus improvement in OCD patients
in combination with fluvoxamine treated with cognitive behaviour
in the treatment of obsessive therapy and pharmacotherapy,
compulsive disorder, J Nerv Ment Acta Psychiatr Scand (1997)
Dis (1998) 186(8):492–9. 96(5):354–61.
46 Marks IM, Lelliott P, Basoglu M, 53 Foa EB, Grayson JB, Steketee
Clomipramine, self-exposure and GS, Doppelt HG, Turner RM,
therapist-aided exposure for Latimer PR, Success and failure
obsessive-compulsive rituals, Br J in the behavioral treatment of
Psychiatry (1988) 152:522–34. obsessive-compulsives, J Consult
Clin Psychol (1983) 51(2):
47 Khanna S, Kumar R, The efficacy 287–97.
of addition of cognitive therapy to
fluoxetine in the treatment of 54 Kozak MJ, Foa EB, Obsessions,
OCD. Third International OCD overvalued ideas, and delusions
Conference, Madeira, Portugal, in obsessive-compulsive disor-
1998. der, Behav Res Ther (1994)
32(3):343–53.
48 McDougle CJ, Goodman WK, 55 Buchanan AW, Meng KS, Marks
Leckman JF, Lee NC, Heninger IM, What predicts improvement
GR, Price LH, Haloperidol addi- and compliance during the
tion in fluvoxamine-refractory behavioral treatment of obsessive
obsessive-compulsive disorder. A compulsive disorder? Anxiety
double-blind, placebo-controlled
(1996) 2(1):22–7.
study in patients with and without
tics, Arch Gen Psychiatry (1994) 56 Castle DJ, Predictors of outcome
51(4):302–8. in the behavioural treatment of
OCD [letter; comment], Br J Psy-
49 Pato MT, Hill JL, Murphy DL, A chiatry (1995) 166(4):540–1.
clomipramine dosage reduction
57 Baer L, Jenike MA, Personality
study in the course of long-term
disorders in obsessive compul-
treatment of obsessive-
compulsive disorder patients, sive disorder, Psychiatr Clin North
Psychopharmacol Bull (1990) Am (1992) 15(4):803–12.
26(2):211–14. 58 Jenike MA, Baer L, Minichiello
WE, Schwartz CE, Carey RJ, Con-
50 Pato MT, Zohar KR, Zohar J, Mur- comitant obsessive-compulsive
phy DL, Return of symptoms after disorder and schizotypal person-
discontinuation of clomipramine ality disorder, Am J Psychiatry
in patients with obsessive- (1986) 143(4):530–2.
chiatry (1988) 145(12):1521–5. 59 Baer L, Jenike MA, Ricciardi JD,
Standardized assessment of per-
51 DeVeaugh GJ, Katz R, Landau P, sonality disorders in obsessive-
Goodman W, Rasmussen S, Clini- compulsive disorder, Arch Gen
cal predictors of treatment Psychiatry (1990) 47(9):826–30.
response in obsessive compul-
60 Mataix CD, Rauch SL, Manzo PA,
sive disorder: exploratory analy-
Jenike MA, Baer L, Use of factor-
ses from multicenter trials of
analyzed symptom dimensions to
clomipramine, Psychopharmacol
predict outcome with serotonin
Bull (1990) 26(1):54–9.
reuptake inhibitors and placebo
52 De Haan E, van Oppen P, van in the treatment of obsessive-
Balkom AJ, Spinhoven P, Hoog- compulsive disorder, Am J Psy-
duin KA, van Dyck R, Prediction chiatry (1999) 156(9):1409–16.
Psychotherapy 133
61 Münchau N, Hand I, Schaible R, 63 Schwartz JM, Stoessel PW, Baxter

Aufbau von Selbsthilfegruppen LJ, Martin KM, Phelps ME, Sys-
für Zwangskranke, Verhaltens- tematic changes in cerebral
therapie (1996) 6:143–61. glucose metabolic rate after suc-
62 Baxter LJ, Schwartz JM, Bergman cessful behavior modification
KS, Caudate glucose metabolic treatment of obsessive-compulsive
rate changes with both drug and disorder, Arch Gen Psychiatry
behavior therapy for obsessive- (1996) 53(2):109–13.
compulsive disorder, Arch Gen
Psychiatry (1992) 49(9):681–9.
11
Treatment of refractory OCD
Christopher J McDougle and Kelda H Walsh
The effectiveness of potent serotonin reuptake inhibitors (SRIs) and expo-

sure with response prevention behavior therapy is now well established
in the treatment of obsessive compulsive disorder (OCD). Despite these
advances, nearly 40–60% of patients experience minimal to no improve-
ment in symptoms with these treatments. Furthermore, in patients who do
respond to SRI or behavior modification treatment, the degree of
improvement is typically incomplete; few patients experience full symp-
tom remission.1
Most large-scale, controlled studies of SRIs in OCD have defined treat-
ment response by a 25–35% decrease from baseline on the total score of
the Yale–Brown Obsessive Compulsive Scale (Y-BOCS, see Appendix 1,
p. 183).2,3 This magnitude of change typically results in significant
improvement in function; however, interfering symptoms usually persist.
Others have required that this criterion be met, along with a categorical
response of ‘much improved’ or ‘very much improved’ on the global
improvement item of the Clinical Global Impression (CGI) scale. In some
studies, ‘marked responders’ have been patients who have met both of
these response criteria, whereas ‘partial responders’ have been patients
who have met one or the other criterion. Patients who demonstrate only a
partial response or are unimproved following 10–12 week trials of two dif-
ferent selective SRIs (SSRIs) and the non-selective SRI clomipramine at
adequate dosages, and who have shown no improvement with at least
20–30 hours of documented exposure with response prevention, should
be considered for the alternative treatment approaches described in this
chapter.
Results from controlled and uncontrolled investigations of various somatic
interventions for patients with ‘treatment-refractory’ OCD have been pub-
lished. These treatments have included the use of standard pharmacologic
agents in higher dosages or administered via an alternative route (e.g. intra-
venous rather than oral clomipramine), combination drug treatment strate-
gies, and the use of novel compounds. Studies of electroconvulsive
therapy, repetitive transcranial magnetic stimulation and neurosurgery have
also been conducted. This chapter will briefly review these data.
135
High-dose SRIs
Controlled studies of SSRIs administered in doses greater than those rec-
ommended by the Food and Drug Administration (FDA) have not been
conducted. Case reports exist describing significant improvement in OC
symptoms in two adult patients, one given sertraline 300 mg per day and
the other citalopram 160 mg per day.4,5 Both patients had received prior
treatment with adequate trials of other SRIs, along with these particular
medications at maximum recommended doses, without meaningful
improvement. In contrast to SSRIs, clomipramine should generally not be
given in doses greater than 250 mg per day owing to the risks of cardio-
toxicity and seizures.
Intravenous clomipramine
Some patients have benefited from receiving clomipramine intravenously

rather than by mouth. For example, a double-blind, placebo-controlled
study of 14 daily intravenous (IV) infusions of clomipramine in adults with
OCD refractory to or intolerant of oral clomipramine, and in many instances
SSRIs, found the drug to be more effective than placebo.6 Six of 29 patients
randomized to IV clomipramine versus none of 25 patients given placebo
were categorized as responders after the 14 infusions. Statistically signifi-
cant improvement was found on some but not all measures of OC symptom
severity. No serious adverse effects occurred. The authors hypothesized
that the preferential efficacy of IV over oral clomipramine might be due to
the greater bioavailability of the more serotonergic parent compound
clomipramine compared with the more noradrenergic metabolite desmethyl-
clomipramine, as a result of bypassing the first-pass hepatoenteric metabo-
lism through the IV route. It has not been determined if patients who improve
with IV clomipramine maintain their response when switched to oral medica-
tion. Liquid clomipramine for IV administration is not approved by the FDA
for use in the USA, although it is available in many European countries and
Canada. Further research on this treatment approach is in progress, includ-
ing attempts to study IV versus oral pulse loading of clomipramine.7
Combination drug treatment strategies
Researchers have been pursuing two primary directions of combination

drug treatment strategies for patients unimproved or only minimally
improved following adequate trials of SRIs.8,9 The first involves adding
drugs that may further enhance serotonin (5-hydroxytryptamine, 5-HT)
function to ongoing SRI administration. This approach has proved partic-
ularly effective in refractory major depressive disorder, where lithium aug-
mentation of antidepressant treatment has been shown to be a useful
Treatment of refractory OCD 137
intervention.10 The second approach has been to add a dopamine (DA)

receptor antagonist, such as a typical or atypical antipsychotic, to SRI
therapy. The antipsychotic addition strategy has been largely based on
phenomenological and genetic data linking some forms of OCD with
chronic tic disorders such as Tourette’s syndrome.11
SRIs plus drugs affecting 5-HT function

A number of drugs affecting 5-HT function, including tryptophan, fenflu-
ramine, lithium, buspirone, clonazepam and pindolol, have been investi-
gated for their potential to decrease OC symptoms when added to
ongoing treatment with SRIs. The combination of clomipramine and an
SSRI has also been studied.
Tryptophan
The addition of tryptophan, the amino acid precursor of 5-HT, to
clomipramine treatment significantly improved OC symptoms in a single
case study.12 Others, however, have not found this approach to be use-
ful,13 and no controlled studies of this additional strategy have been pub-
lished. Adverse neurological reactions resembling the 5-HT syndrome
have been reported when tryptophan is used in combination with fluoxe-
tine.14 Furthermore, oral tryptophan is currently unavailable in the USA
because of evidence linking some preparations with the eosinophilia
myalgia syndrome.15 Benefits of adding open-label tryptophan, up to 8 g
per day, to an ongoing combination of SSRI and pindolol were reported
by Blier and Bergeron in Canada (see below).16
Fenfluramine
Fenfluramine was recently withdrawn from the US market owing to con-
cern that it contributed to the development of cardiac valvular disease.17
It had previously been marketed for the treatment of obesity under the
trade name Pondimin. Hollander et al reported that the addition of open-
label D,L-fenfluramine, an indirect 5-HT agonist, to ongoing SRI treatment
led to improvement in OC symptoms in six of seven patients.18 In another
report, two patients on clomipramine were observed to improve following
the addition of D-fenfluramine, which is believed to have more specific
effects on 5-HT transport and release than the racemic mixture, but
which is also unavailable in the USA.19 Some studies in laboratory ani-
mals have suggested that fenfluramine may be neurotoxic.20 Furthermore,
no controlled study of this combination treatment approach supporting its
efficacy has been published.
Lithium
Lithium has been suggested to potentiate antidepressant-induced
increases in 5-HT neurotransmission by enhancing presynaptic 5-HT
release in some areas of the brain.21 Although individual case reports sug-
gested that lithium may further reduce OC symptoms when added to ther-
apy with antidepressants,22–24 including SRIs,12,24–26 controlled studies have
not substantiated these clinical observations.27,28 Based on these results, the
addition of lithium to ongoing SRI treatment of OCD does not appear to
approach the rate or quality of response typically observed in
antidepressant-refractory depression.10 Clinical experience suggests that
lithium augmentation of ongoing SRI therapy may be an option for patients
who have primary major depressive disorder with secondary OC symptoms.
Buspirone
Buspirone is a 5-HT1A receptor partial agonist and its chronic administration
has been shown in preclinical studies to enhance 5-HT neurotransmission.29
Results from two open-label studies of buspirone as an adjunct to fluoxetine
treatment indicated that this approach led to a greater reduction in OC
symptoms than did treatment with fluoxetine alone.30,31 However, results
from three double-blind, placebo-controlled studies of buspirone addition in
adult OCD patients refractory to SRI monotherapy have not corroborated
these initial reports.32–34 Based on the authors’ clinical experience, the addi-
tion of buspirone to SRI treatment can at times improve depressive symp-
toms in OCD patients with comorbid major depressive disorder.
In light of the efficacy of SRIs in OCD, presumably partly due to their
ability to enhance central 5-HT neurotransmission, a better response to
the controlled addition of lithium and buspirone might have been pre-
dicted. Both of these drugs have been shown to facilitate 5-HT function in
the brain when given over time.29,35 This neurochemical effect, however,
may not be sufficient for achieving efficacy in the treatment of OCD. Blier
and de Montigny have pointed out that the lack of response to lithium
augmentation in OCD may be due to differential regional effects of lithium
on 5-HT release in the central nervous system.36 The same may be true
for buspirone. For instance, preclinical studies have shown that lithium
can enhance 5-HT release in the spinal cord,37 hypothalamus,38 and hip-
pocampus,39 whereas quantitative autoradiographic techniques have
demonstrated high densities of 5-HT1A receptors in the hippocampus, lat-
eral septum, entorhinal cortex, and central amygdala.40 In contrast, the
cerebral cortex, caudate putamen, globus pallidus and substantia nigra,
areas of the brain demonstrated to mediate some forms of OC phenom-
ena, have not been found to be integrally involved in the mechanism of
action of these two drugs.40–42 Thus, although both agents may increase
5-HT neurotransmission in the brain, the activity may not be occurring in
areas relevant to the treatment of OCD.
Clonazepam
Evidence from studies in laboratory animals and humans suggests that
the benzodiazepine clonazepam may have effects on 5-HT function
unlike those of other drugs in its class.43 In a 4-week double-blind,

placebo-controlled crossover study of clonazepam addition (3–4 mg per
day) to ongoing fluoxetine or clomipramine, Pigott et al found significant
improvement in one of three measures of OCD, but not the Y-BOCS.44
The patients did show a significant reduction in ratings of anxiety. To our
knowledge, this study has not been published beyond abstract form. In
general, benzodiazepines may help secondary anxiety but are usually
not effective for reducing the core symptoms of OCD.
Pindolol
The addition of pindolol to antidepressants has been reported to
enhance or quicken response in adults with major depression in some45,46
but not all studies.47 Pindolol is hypothesized to act as a presynaptic
5-HT1A antagonist, blocking somatodendritic 5-HT1A autoreceptors on the
cell bodies of 5-HT neurons in the midbrain raphe nuclei from the effects
of acute increases in synaptic 5-HT induced by the antidepressant
drug.48 This action possibly antagonizes the usual resultant decrease in
firing rate of the neuron and 5-HT release and thus hastens and facilitates
5-HT neurotransmission. In an open-label trial by Koran et al, pindolol
2.5 mg three times a day to 5.0 mg twice a day, for 2 weeks to 5 months,
was added to ongoing SRI in eight adults with OCD who were minimally
improved on their previous regimen.49 One patient showed a complete
resolution of OC symptoms within 4 days of pindolol addition, which was
maintained during a 5-month follow-up. None of the other seven patients,
however, had any significant improvement. In another open-label study,
pindolol 2.5 mg three times a day for 4 weeks was added to ongoing SRI
treatment in 13 patients minimally improved on SRI alone.16 Four patients
showed a meaningful improvement in OC symptoms as measured with
the Y-BOCS. Of these four patients, three had comorbid major depres-
sion which improved markedly with pindolol addition. Overall, however,
there was no significant group effect of pindolol addition on OC symp-
toms. To our knowledge, no controlled study of pindolol addition to SRIs
in OCD has been published. These open-label reports suggest that this
approach may be useful for the comorbid depressive symptoms of OCD
but that it is unlikely to benefit the core OC symptoms for most patients.
Combining SRIs
No controlled study of the simultaneous administration of two SSRIs has
been published in the treatment of OCD. A small open-label case series
has described encouraging results with the coadministration of
clomipramine and fluoxetine in adolescents with OCD.50 Initially, six
patients, mean age 14.8 years, were given clomipramine, mean dosage
92 mg per day, for a mean duration of 17.5 weeks. Three patients
showed moderate improvement, whereas the other three were minimally
improved on clomipramine alone. With combined clomipramine–
fluoxetine treatment, clinical global improvement was marked in five

patients and moderate in one within weeks to months of adding fluox-
etine. Optimal daily doses of clomipramine were 50 mg in four patients
and 25 mg in two, and those of fluoxetine were 20 mg in four patients and
60 mg in two. The authors concluded that relatively low doses of a
clomipramine–fluoxetine combination result in greater clinical global
improvement, broader symptomatic relief, and fewer adverse effects in
adolescents with OCD than with therapeutic doses of clomipramine
alone. The beneficial effects of a clomipramine–fluoxetine combination
have also been reported in three adult cases of severe OCD.51 In a retro-
spective, open-label case series, seven children and young adults aged
9–23 received combined clomipramine–SSRI treatment with beneficial
results.52 None of the patients was able to tolerate high doses of either
medication alone and all remained significantly impaired on mono-
therapy. Doses of clomipramine ranged from 25 mg to 100 mg daily in
combination with different SSRIs. Two patients developed tachycardia
and prolongation of the corrected QT interval on electrocardiography with
the combined treatment. Because of the risk of SSRI-induced elevations of
plasma levels of tricyclic antidepressants, including clomipramine,
extreme caution should be used when giving these drugs concurrently.
Because of clomipramine’s potential to lower the seizure threshold and
impede cardiac conduction, it is important to obtain clomipramine blood
levels before and after the administration of an SSRI. Serial electrocardio-
grams should be obtained if this strategy is employed.
SRIs plus drugs affecting dopamine function

There has been no published controlled study of dopamine receptor
antagonist monotherapy in the treatment of OCD as defined by the Diag-
nostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV).53
In our clinical experience, DA receptor blockers are not effective when
used alone for the treatment of OCD. However, these drugs remain the
most effective treatment for tics, such as those typical of Tourette’s syn-
drome.54 In light of the phenomenologic, neurobiologic and genetic over-
lap between Tourette’s syndrome and some forms of OCD,55 the role of
typical and atypical antipsychotic drugs as adjunctive treatments for
SRI-refractory OCD has been explored.
Typical antipsychotic drugs

Pimozide
In an open-label case series, typical antipsychotics, primarily pimozide
(6.5 mg per day), were added to ongoing treatment in 17 non-psychotic
adult OCD patients unresponsive to fluvoxamine with or without lithium.56
Nine of 17 patients were rated as ‘much improved’ or ‘very much
improved’ on the CGI scale within 2–8 weeks of pimozide addition. Seven
of eight patients with comorbid chronic tic disorder or schizotypal per-
sonality disorder were responders compared with only two of nine
patients without this comorbidity.
Haloperidol
In a double-blind comparison with placebo, haloperidol (mean dose
6.2 mg per day) was significantly more effective when added to ongoing
treatment in adult OCD patients unimproved on fluvoxamine alone.57 Sig-
nificant improvement was observed beginning 3 weeks after haloperidol
addition. Eleven of 17 patients randomly assigned to receive haloperidol
were rated as responders after 4 weeks of treatment compared with none
of 17 patients who received placebo. Patients with a comorbid tic disor-
der showed a preferential response. Because of the small number of
patients with comorbid schizotypal personality disorder in this investiga-
tion, it was not possible to make definitive conclusions about the useful-
ness of this approach for these patients. Based upon our clinical
experience since completion of the study, we now typically begin
haloperidol 0.25–0.5 mg per day, with subsequent increases every 4–7
days to a maximum of 2–4 mg per day, as clinically indicated. We have
found that when this treatment strategy is effective, response will usually
occur with lower doses of the DA receptor blocker than previously
described, and usually within 2–4 weeks of addition to the SRI.
Atypical antipsychotic drugs

The atypical antipsychotic drugs, which modulate both DA and 5-HT
function, and may be associated with lower risks of acute extrapyramidal
side effects and chronic dyskinesias, have received increasing attention
as potential treatments for SRI-refractory OCD.
Clozapine
The first atypical antipsychotic agent to be systematically evaluated in OCD
was clozapine. The study was an open-label trial of clozapine monotherapy
in 12 adults with refractory OCD.58 Ten of 12 patients who entered the study
completed the 10-week trial. Two patients dropped out prematurely due to
sedation (100 mg per day for 3 weeks) and hypotension (125 mg per day
for 2 weeks), respectively. The mean daily dose of clozapine in the 10 com-
pleters was 462.5 mg. Clozapine was not associated with any statistically
significant improvement in OC or depressive symptoms or in a global mea-
sure of change. None of the patients met criteria for treatment response. To
our knowledge, no report of clozapine addition to SRI treatment in OCD has
appeared, and no controlled study has been conducted.
Risperidone
Clinical experience with risperidone in the treatment of SRI-refractory
OCD appears more promising than that with clozapine. To our knowl-
edge, successful use of risperidone monotherapy in OCD has not been
reported. Multiple open-label reports, however, have suggested that
adding risperidone to ongoing SRI treatment in OCD patients minimally
improved or unimproved on the SRI can be of significant benefit.59–62
Interestingly, in contrast to the results from the study of haloperidol addi-
tion, it appears that patients with and without comorbid chronic tic dis-
orders may respond to risperidone addition. The dosages of risperidone
that appear helpful seem to be substantially lower (0.25 mg to 3 mg per
day) than those generally employed for the treatment of psychotic symp-
toms in other patient populations. Furthermore, a decrease in OC symp-
toms is often observed within days of adding risperidone. Results from a
double-blind, placebo-controlled study of risperidone addition to ongoing
SRI treatment in adults with OCD are encouraging.63 Fifty per cent of
patients who were randomized to 6 weeks of risperidone (mean dose
2.2 mg per day) addition to ongoing SRI treatment were categorized as
responders, compared with none of those who received placebo. There
was no difference in treatment response between OCD patients with and
without comorbid diagnoses of chronic tic disorders, and the drug was
well tolerated.
Olanzapine
In an open-label study of olanzapine addition to ongoing SRI treatment in
adults with OCD, ten patients who showed no response or partial
improvement following an adequate SSRI trial were given olanzapine
(mean dosage 7.3 mg per day) in conjunction with ongoing SRI for 8
weeks.64 Four patients were categorized as responders, three as partial
responders, and two as unchanged. The tenth patient discontinued olan-
zapine after only 3 weeks because of excessive sedation, in spite of
apparent improvement in OC symptoms. Of the patients who completed
the 8-week trial, one reported no side effects, seven reported sedation,
and one experienced weight gain of 3.6 kg (8 lb).
To our knowledge, no report describing the use of the atypical antipsy-
chotic quetiapine in OCD has appeared.
Bromocriptine
An open-label case series described a significant reduction in OC and
depressive symptoms during chronic monotherapy with the DA receptor
agonist bromocriptine (12.5–30 mg per day), in three of four adults with
OCD and comorbid major depression.65 Caution should be used with this
approach because of the potential for the induction or exacerbation of
tics. No controlled study of bromocriptine as monotherapy or an adjunc-
tive treatment has been conducted in OCD.
SRIs plus drugs affecting other systems

Triiodothyronine
Sixteen adults with OCD who were partially improved on clomipramine
received 4 weeks of triiodothyronine (liothyronine) 25 µg per day under
double-blind conditions.27 Thyroid hormone was not associated with any
clinically meaningful change in OC or depressive symptoms.
Desipramine
Clomipramine has potent effects on both 5-HT and norepinephrine (nor-
adrenaline) uptake. Based upon this mechanism of action, it has been
suggested that effects on both neurochemical systems might be relevant
to the drug’s anti-OC efficacy. To address this question, Barr et al con-
ducted a placebo-controlled study to investigate the addition of
desipramine hydrochloride, a relatively selective norepinephrine reuptake
inhibitor, to the regimen of 23 adults with OCD who were unimproved fol-
lowing 10 weeks of SSRI monotherapy.66 No significant difference was
found between desipramine and placebo, suggesting that
clomipramine’s anti-OC effect is largely mediated by its potent 5-HT,
rather than norepinephrine, reuptake blocking properties.
Gabapentin
The neutral gamma-aminobutyric acid analog gabapentin was reported
to further reduce OC symptoms when added in an open-label manner to
ongoing treatment of five adults with OCD who were partially improved
on fluoxetine 30–100 mg per day.67 After 6 weeks, the mean daily dose of
gabapentin was 2520 mg. Other than transient gastrointestinal side
effects, the combination treatment was generally well tolerated. Accord-
ing to the report, all patients experienced marked subjective improve-
ment in anxiety, OC symptoms, sleep and mood within 2 weeks of
initiating gabapentin. These changes were corroborated by the evalua-
tions of the clinical staff and supported by rating data when available. A
double-blind, placebo-controlled study of this approach is reportedly cur-
rently under way by this research group.
A summary of the results of studies of combination drug treatment is
given in Table 11.1.
Novel compounds
Inositol
The phosphatidylinositol cycle is the second messenger system for sev-
eral neurotransmitters, including several subtypes of 5-HT receptors.
Inositol (18 g per day), a simple polyol second messenger precursor,
was administered to 15 adults with OCD in a double-blind, placebo-
Table 11.1 Double-blind, placebo-controlled drug studies in adults with

treatment-refractory obsessive compulsive disorder.
May be effective:
• Intravenous clomipraminea
• Adding clonazepamb
• Adding haloperidolc
• Adding risperidone
• Inositol monotherapyd
Apparently ineffective:
• Adding lithium
• Adding buspirone
• Adding triiodothyronine (liothyronine)
• Adding desipramine
a
Remains investigational in the USA.
b
Only a small number of subjects studied, and improvement not evident on all OCD rating scales.
c
Primarily in ‘tic-related’ OCD.
d
A relatively small number of subjects were studied; remains investigational.
controlled crossover study (6 weeks each on drug and placebo).68 For

the 13 patients who completed the study, inositol resulted in a significant
reduction in Y-BOCS scores compared with placebo, but no difference
was shown between the two on the Hamilton depression or anxiety
scales. No side effects occurred.
Tramadol
Tramadol is an opioid agonist which also inhibits the reuptake of 5-HT
and norepinephrine (noradrenaline). Seven adults with SRI-refractory
OCD entered a 6-week open-label study of tramadol.69 Two patients dis-
continued the trial prematurely, the first during week 1 owing to nausea
and exacerbation of trichotillomania, and the other during week 6 after
experiencing a panic attack. The mean daily dose of tramadol for the six
patients completing at least 2 weeks of treatment was 254 mg. After 6
weeks Y-BOCS scores were significantly reduced (by 26%), whereas
Hamilton depression scores were not significantly different. The most fre-
quent side effects were decreased appetite, insomnia, itching, sedation,
dizziness and nausea. Three patients elected to continue treatment with
the drug at the end of the trial.
Flutamide
Flutamide is a synthetic, non-steroidal, competitive antagonist of the
androgen receptor. In an 8-week open-label study of flutamide, up to
750 mg per day, no significant improvement in OC, depressive or anxiety
symptoms was found in eight adults with OCD.70 The results from this
study are consistent with two previous reports of the antiandrogen cypro-
terone acetate which showed lack of sustained effect71 and no effect,72
respectively, in adults with OCD.
Sumatriptan
Sumatriptan is a 5-HT1D agonist that is marketed for the treatment of
migraine headache. In an open-label report, sumatriptan (100 mg per
day) was given for 4 weeks to three adults with severe treatment-
refractory OCD.73 The drug reportedly led to a significant improvement in
depressive symptoms and a modest reduction in OC symptoms. Upon
discontinuation, symptoms returned in all three patients. No adverse
effects were reported. As sumatriptan has been reported to penetrate the
blood–brain barrier poorly, the mechanism of action of this drug in OCD
remains unclear. To our knowledge, no controlled investigation of suma-
triptan in OCD has been published.
Treatments warranting further study are listed in Table 11.2.
Other somatic treatments
Electroconvulsive therapy
In general, electroconvulsive therapy has not been considered an effec-
tive treatment for OCD. One report described a greater than 20% reduc-
tion in symptoms in a series of nine patients with treatment-refractory
OCD without comorbid depression.74 However, OC symptoms returned to
pretreatment levels within 4 months.
Table 11.2 Promising treatments which may warrant controlled study

for treatment-refractory obsessive compulsive disorder.
• Higher-dose SSRI monotherapy
• Adding pindolol
• Combined SSRI–clomipramine treatment
• Adding pimozide
• Adding olanzapine
• Bromocriptine monotherapy
• Adding gabapentin
• Tramadol monotherapy
• Sumatriptan monotherapy
• Repetitive transcranial magnetic stimulation
• Neurosurgery (gamma knife surgery)
Repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is a procedure in
which a pulsatile high-intensity electromagnetic field is emitted from a
coil placed against the scalp, resulting in focal electrical currents in the
underlying cerebral cortex. Preliminary results from a controlled study by
Greenberg et al suggest that a single application of rTMS to the right pre-
frontal cortex produces a transient reduction of compulsive urges.75 As
seizures have occurred in some subjects receiving rTMS, the procedure
is not without risk. Further study of rTMS as a potential treatment for OCD
is continuing.
Neurosurgery
When non-surgical treatments have failed to improve OC symptoms signif-
icantly in severely ill patients, at least partial relief can be obtained by
some patients with neurosurgery. According to a review of this topic by
Jenike, to be considered a candidate for a neurosurgical approach,
patients must fail to improve following treatment with all available and
appropriate psychotropic medications, as well as behavioral treatments.76
Prior to being considered for surgery, each patient should have had ade-
quate trials of clomipramine, fluoxetine, fluvoxamine, sertraline, paroxetine
and a monoamine oxidase inhibitor, as well as augmentation of at least
one of the above drugs for 1 month with at least two of the following:
lithium, clonazepam and buspirone. If the patient has tics, a trial of aug-
mentation with a low-dose neuroleptic should be performed. All patients
must also have had an extended trial of behavior therapy consisting of
exposure and response prevention. The illness must have been subject to
intensive psychiatric treatment for such a lengthy period that it is, indeed,
clearly refractory to standard treatment. In practice, most neurosurgical
centers define this as a minimum of 5 years’ duration. Various contraindi-
cations also apply. In his review of the literature, Jenike concluded that,
without further research, no definitive conclusions can be drawn as to
which particular surgical procedure is the most effective among cingulo-
tomy, anterior capsulotomy, limbic leukotomy and subcaudate tractotomy.
Results from thermocapsulotomy and gamma knife capsulotomy
appear promising.77 Preliminary pilot data from a controlled study of
gamma knife surgery, where lesions are made in the anterior limb of the
internal capsule as it passes up through the striatum from the dorso-
medial and anterior thalamic nuclei to their projection sites in the orbito-
medial frontal and cingulate cortices, have shown positive benefits.78 In
fact, efficacy has been demonstrated in 40–50% of the treatment-
refractory patients receiving the active procedure with no significant
acute or long-term side effects. Further double-blind studies to confirm
efficacy and establish safety are needed.
Conclusion
This chapter has reviewed somatic interventions for patients with
treatment-refractory OCD. Table 11.1 lists drug treatments that have
been shown in double-blind, placebo-controlled studies to be either
effective or ineffective for these patients. With regard to the negative
studies listed in this table, it should be stated that such treatments may
prove helpful for the individual patient. Treatments that appear promising,
based upon open-label study results, and may warrant further systematic
investigation, are listed in Table 11.2. Treatments that are likely to be inef-
fective, based upon open-label data, are listed in Table 11.3.
In addition to future controlled studies of these promising interventions,
one area that warrants increased attention is the treatment of children
and adolescents with refractory OCD. Preliminary reports suggest that
combination drug treatments may be effective, but controlled studies of
safety and efficacy are needed.79,80
Acknowledgments
The authors would like to thank Krista Guenin BA and Mrs Robbie Smith
for their assistance in preparation of the manuscript. This work was sup-
ported, in part, by the Theodore and Vada Stanley Research Foundation
(Dr McDougle), an Independent Investigator Award – Seaver Investigator
from the National Alliance for Research on Schizophrenia and Depres-
sion (Dr McDougle), a Research Unit on Pediatric Psychopharmacology
contract (N01MH70001) from the National Institute of Mental Health (Dr
McDougle), and the State of Indiana Department of Mental Health.
Table 11.3 Treatments unlikely to be effective for treatment-refractory

obsessive compulsive disorder.
• Adding tryptophan
• Adding fenfluramine
• Clozapine monotherapy
• Flutamide monotherapy
• Electroconvulsive therapy
References
1 McDougle CJ, Goodman WK, compulsive disorder, Psychiatr
Leckman JF et al, The psychophar- Ann (1998) 28:641–9.
macology of obsessive compulsive 10 Price LH, Heninger GR, Lithium in
disorder: implications for treatment the treatment of mood disorders,
and pathogenesis, Psychiatr Clin N Engl J Med (1994) 331:591–8.
North Am (1993) 16:749–66.
11 McDougle CJ, Goodman WK,
2 Goodman WK, Price LH, Ras- Price LH, Dopamine antagonists in
mussen SA et al, The Yale-Brown tic-related and psychotic spectrum
Obsessive Compulsive Scale obsessive compulsive disorder, J
(Y-BOCS): Part I. Development, Clin Psychiatry (1994) 55(suppl. 3):
use, and reliability, Arch Gen Psy-
24–31.
chiatry (1989) 46:1006–11.
12 Rasmussen SA, Lithium and tryp-
3 Goodman WK, Price LH, Ras-
tophan augmentation in
mussen SA et al, The Yale-Brown
clomipramine resistant obsessive-
Obsessive Compulsive Scale
(Y-BOCS): Part II. Validity, Arch
chiatry (1984) 141:1283–5.
Gen Psychiatry (1989) 46:
1012–16. 13 Mattes J, A pilot study of com-
4 Byerly MJ, Goodman WK, Chris- bined trazodone and tryptophan
tensen R, High doses of sertraline in obsessive-compulsive disor-
for treatment-resistant obsessive- der. Int Clin Psychopharmacol
compulsive disorder, Am J Psy- (1986) 1:170–3.
chiatry (1996) 153:1232–3. 14 Steiner W, Fontaine R, Toxic reac-
5 Bejerot S, Bodlund O, Response tion following the combined
to high doses of citalopram in administration of fluoxetine and L-
treatment-resistant obsessive- tryptophan: five case reports. Biol
compulsive disorder, Acta Psych Psychiatry (1986) 21:1067–71.
Scand (1998) 98:423–4. 15 Slutsker L, Hoesly FC, Miller L et al,
6 Fallon BA, Liebowitz MR, Eosinophilia-myalgia syndrome
Campeas R et al, Intravenous associated with exposure to trypto-
clomipramine for obsessive- phan from a single manufacturer,
compulsive disorder refractory to JAMA (1990) 264: 213–17.
oral clomipramine: a placebo- 16 Blier P, Bergeron R, Sequential
controlled study, Arch Gen Psy- administration of augmentation
chiatry (1998) 55:918–24. strategies in treatment-resistant
7 Koran LM, Sallee FR, Pallanti S, obsessive-compulsive disorder:
Rapid benefit of intravenous preliminary findings, Int Clin Psy-
pulse loading of clomipramine in chopharmacol (1996) 11:37–44.
obsessive-compulsive disorder, 17 Connolly HM, Crary JL, McGoon
Am J Psychiatry (1997) 154: MD et al, Valvular heart disease
396–401. associated with fenfluramine-
8 McDougle CJ, Update on phar- phentermine, N Engl J Med
macologic management of OCD: (1997) 337:581–8.
agents and augmentation, J Clin 18 Hollander E, DeCaria CM,
Psychiatry (1997) 58(suppl. 12): Schneier FR et al, Fenfluramine
11–17. augmentation of serotonin reup-
9 Goodman WK, Ward HE, Murphy take blockade antiobsessional
TK, Biologic approaches to treatment, J Clin Psychiatry
treatment-refractory obsessive- (1990) 51:119–23.
19 Judd FK, Chua P, Lynch C et al, A role for the serotonin system in
Fenfluramine augmentation of the mechanism of action of anti-
clomipramine treatment of obses- depressant treatments: preclinical
sive compulsive disorder, Austr evidence, J Clin Psychiatry (1990)
NZ J Psychiatry (1991) 25: 51(suppl. 4):14–20.
412–14. 30 Markovitz PJ, Stagno SJ, Cal-
20 Schuster C, Lewis M, Seiden L, abrese JR, Buspirone augmenta-
Fenfluramine: neurotoxicity, Psy- tion of fluoxetine in obsessive-
chopharm Bull (1986) 22:148–51. compulsive disorder, Am J Psy-
21 De Montigny C, Enhancement of chiatry (1990) 147:798–800.
the 5-HT neurotransmission by 31 Jenike MA, Baer L, Buttolph L,
antidepressant treatments, J Buspirone augmentation of fluox-
Physiol (1981) 77:455–61. etine in patients with obsessive
22 Stern TA, Jenike MA, Treatment of compulsive disorder, Am J Clin
obsessive-compulsive disorder Psychiatry (1991) 52:13–14.
with lithium carbonate, Psychoso- 32 Pigott TA, L’Heureux F, Hill JL et
matics (1983) 24:671–3. al, A double-blind study of adju-
23 Eisenberg J, Asnis G, Lithium as vant buspirone hydrochloride in
an adjunct treatment in obsessive- clomipramine-treated patients
compulsive disorder, Am J Psy- with obsessive-compulsive disor-
chiatry (1985) 142:663. der, J Clin Psychopharmacol
(1992) 12:11–18.
24 Golden RN, Morris JE, Sack DA,
Combined lithium-tricyclic treat- 33 McDougle CJ, Goodman WK,
ment of obsessive-compulsive Leckman JF et al, Limited thera-
disorder, Biol Psychiatry (1988) peutic effect of addition of bus-
23:181–5. pirone in fluvoxamine-refractory
obsessive compulsive disorder,
25 Feder R, Lithium augmentation of Am J Psychiatry (1993) 150:
clomipramine, J Clin Psychiatry 647–9.
(1988) 49:458.
34 Grady TA, Pigott TA, L’Heureux F
26 Ruegg RG, Evans DL, Comer WS, et al, Double-blind study of adju-
Lithium plus fluoxetine treatment vant buspirone for fluoxetine-
of obsessive compulsive disor- treated patients with obsessive-
der, New Research Abstr. 92, compulsive disorder, Am J Psy-
143rd Annual Meeting of the chiatry (1993) 150:819–21.
American Psychiatric Association,
New York 1990; 81. 35 De Montigny C, Cournoyer G,
Morissette R et al, Lithium car-
27 Pigott TA, Pato MT, L’Heureux F bonate addition in tricyclic
et al, A controlled comparison of antidepressant-resistant unipolar
adjuvant lithium carbonate or thy- depression: correlations with the
roid hormone in clomipramine- neurobiologic actions of tricyclic
treated patients with obsessive- antidepressant drugs and lithium
compulsive disorder, J Clin Psy- ion on the serotonin system, Arch
chopharmacol (1991) 11:242–8. Gen Psychiatry (1983) 40:
28 McDougle CJ, Price LH, Good- 1327–34.
man WK et al, A controlled trial of 36 Blier P, de Montigny C, Lack of
lithium augmentation in fluvoxa- efficacy of lithium augmentation in
mine-refractory obsessive com- obsessive-compulsive disorder:
pulsive disorder: lack of efficacy, the perspective of different
J Clin Psychopharmacol (1991) regional effects of lithium on
11:175–84. serotonin release in the central
29 Blier P, de Montigny C, Chaput Y, nervous system, J Clin Psy-
chopharmacol (1992) 12:65–6. ton, DC, 1992; 82.

37 Sangdee C, Franz DN, Lithium 45 Artigas F, Romero L, de Montigny
enhancement of 5-HT transmis- C et al, Acceleration of the effect
sion induced by 5-HT precursors, of selected antidepressant drugs
Biol Psychiatry (1980) 15:59–75. in major depression by 5-HT1A
38 Baptista TJ, Hernandez L, Bur- antagonists, Trends Neurosci
guera JL et al, Chronic lithium (1996) 19:378–83.
administration enhances sero- 46 Blier P, Bergeron R, Effectiveness
tonin release in the lateral hypo- of pindolol with selected antide-
thalamus but not in the pressant drugs in the treatment of
hippocampus in rats: a microdial- major depression, J Clin Psy-
ysis study, J Neural Transm chopharmacol (1995) 15:217–22.
(1990) 82:31–41. 47 Berman RM, Darnell AM, Miller
39 Treiser SL, Cascio CS, O’Dono- HL et al, Effect of pindolol in has-
hue TL et al, Lithium increases tening response to fluoxetine in
serotonin release and decreases the treatment of major depres-
serotonin receptors in the hip- sion: a double-blind, placebo-
pocampus, Science (1981) 213: controlled trial, Am J Psychiatry
1529–31. (1997) 154:37–43.
40 Radja F, Laporte AM, Daval G, 48 Artigas F, Perez V, Alvarez E, Pin-
Autoradiography of serotonin dolol induces a rapid improve-
receptor subtypes in the central ment of depressed patients
nervous system, Neurochem Int treated with serotonin reuptake
(1991) 18:1–15. inhibitors, Arch Gen Psychiatry
41 Friedman E, Hoau-Yan W, Effect (1994) 51:248–51.
of chronic lithium treatment of 49 Koran LM, Mueller K, Maloney A,
5-hydroxytryptamine autorecep- Will pindolol augment the
tors and release of 5[3H]hydroxy- response to a serotonin reuptake
tryptamine from rat brain cortical, inhibitor in obsessive-compulsive
hippocampal, and hypothalamic disorder? J Clin Psychopharma-
slices, J Neurochem (1988) col (1996) 16:253–4.
50:195–201. 50 Simeon JG, Thatte S, Wiggins D,
42 Katz RJ, Chase TN, Irwin JK, Treatment of adolescent
Evoked release of norepinephrine obsessive-compulsive disorder
and serotonin from brain slices: with a clomipramine-fluoxetine
inhibition by lithium, Science combination, Psychopharm Bull
(1968) 162:466–7. (1990) 26:285–90.
43 Wagner HR, Reches A, Yablon- 51 Browne M, Horn E, Jones TT, The
skaya E et al, Clonazepam- benefits of clomipramine-
induced up-regulation of fluoxetine combination in obses-
serotonin-1 and serotonin-2 bind- sive compulsive disorder, Can J
ing sites in rat frontal cortex, Adv Psychiatry (1993) 38:242–3.
Neurol (1986) 43:645–51. 52 Figueroa Y, Rosenberg DR,
44 Pigott TA, L’Heureux FL, Ruben- Birmaher B et al, Combination
stein CS, A controlled trial of clon- treatment with clomipramine and
azepam augmentation in OCD selective serotonin reuptake
patients treated with inhibitors for obsessive-
clomipramine or fluoxetine, New compulsive disorder in children
Research Abstr. 144, 145th and adolescents, J Child Adolesc
Annual Meeting of the American Psych (1998) 8:61–7.
Psychiatric Association, Washing- 53 American Psychiatric Association,
Diagnostic and Statistical Manual 62 Stein DJ, Bouwer C, Hawkridge S

of Mental Disorders, 4th edn et al, Risperidone augmentation
(American Psychiatric Associa- of serotonin reuptake inhibitors in
tion: Washington, DC, 1994). obsessive-compulsive and
54 Leckman JF, Pauls DL, Cohen related disorders, J Clin Psychia-
DJ, Tic disorders. In: Bloom FE, try (1997) 58:119–22.
Kupfer DJ, eds, Psychopharma- 63 McDougle CJ, Epperson CN, Pel-
cology: The Fourth Generation of ton GH et al, A double-blind,
Progress (Raven Press: New placebo-controlled study of
York, 1995) 1665–74. risperidone addition in serotonin
55 Goodman WK, McDougle CJ, reuptake inhibitor-refractory
Price LH et al, Beyond the sero- obsessive-compulsive disorder,
tonin hypothesis: a role for Arch Gen Psychiatry (2000)
dopamine in some forms of 57:794–801.
obsessive compulsive disorder? J 64 Weiss EL, Potenza MN,
Clin Psychiatry (1990) 51(suppl.): McDougle CJ et al, Olanzapine
36–43. addition in obsessive-compulsive
56 McDougle CJ, Goodman WK, disorder refractory to selective
Price LH, Neuroleptic addition in serotonin reuptake inhibitors: an
fluvoxamine-refractory obsessive- open-label case series, J Clin
compulsive disorder, Am J Psy- Psychiatry (1999) 60:524–7.
chiatry (1990) 147:652–4. 65 Ceccherini-Nelli A, Guazzelli M,
57 McDougle CJ, Goodman WK, Treatment of refractory OCD with
Leckman JF et al, Haloperidol the dopamine agonist bromocrip-
addition in fluvoxamine-refractory tine, J Clin Psychiatry (1994)
obsessive compulsive disorder: a 55:415–16.
double-blind, placebo-controlled 66 Barr LC, Goodman WK, Anand A
study in patients with and without et al, Addition of desipramine to
tics, Arch Gen Psychiatry (1994) serotonin reuptake inhibitors in
51:302–8. treatment-resistant obsessive
58 McDougle CJ, Barr LC, Goodman compulsive disorder, Am J Psy-
WK et al, Lack of efficacy of chiatry (1997) 154:1293–5.
clozapine monotherapy in refrac- 67 Cora-Locatelli G, Greenberg BD,
tory obsessive compulsive disor- Martin J et al, Gabapentin aug-
der. Am J Psychiatry (1995) 152: mentation for fluoxetine-treated
1812–14. patients with obsessive-
59 Jacobsen FM, Risperidone in the compulsive disorder, J Clin Psy-
treatment of affective illness and chiatry (1998) 59:480–1.
obsessive compulsive disorder, J 68 Fux M, Levine J, Aviv A et al,
Clin Psychiatry (1995) 56:423–9. Inositol treatment of obsessive-
60 McDougle CJ, Fleischmann RL, compulsive disorder, Am J Psy-
Epperson CN et al, Risperidone chiatry (1996) 153:1219–21.
addition in fluvoxamine-refractory 69 Shapira NA, Keck PE, Goldsmith
obsessive compulsive disorder: TD et al, Open-label pilot study of
three cases, J Clin Psychiatry tramadol hydrochloride in
(1995) 56:526–8. treatment-refractory obsessive-
61 Saxena S, Wang D, Bystritsky A compulsive disorder, Depress
et al, Risperidone augmentation Anx (1997) 6:170–3.
of SRI treatment for refractory 70 Altemus M, Greenberg BD,
obsessive-compulsive disorder, J Keuler D et al, Open trial of flu-
Clin Psychiatry (1996) 57:303–6. tamide for treatment of obsessive-
compulsive disorder, J Clin Psy- 76 Jenike MA, Neurosurgical treat-

chiatry (1999) 60:442–5. ment of obsessive-compulsive
71 Casas M, Alvarez E, Duro P et al, disorder, Br J Psychiatry (1998)
Antiandrogenic treatment of 173(suppl. 35):79–90.
obsessive-compulsive neurosis, 77 Lippitz BE, Mindus P, Meyerson
Acta Psych Scand (1986) 73: BA et al, Lesion topography and
221–2. outcome after thermocapsulo-
72 Feldman JD, Noshirvani H, Chu tomy or gamma knife capsulo-
C, Improvement in female tomy for obsessive-compulsive
patients with severe obsessions disorder: relevance of the right
and/or compulsions treated with hemisphere, Neurosurgery (1999)
cyproterone acetate, Acta Psych 44:452–60.
Scand (1988) 78:254. 78 Rasmussen SA, Eisen JL, Treat-
73 Stern L, Zohar J, Cohen R et al, ment strategies for chronic and
Treatment of severe, drug resis- refractory obsessive-compulsive
tant obsessive compulsive disor- disorder, J Clin Psychiatry (1997)
der with the 5HT1D agonist 58(suppl. 13):9–13.
sumatriptan, Eur Neuropsy- 79 Leonard HL, Topol D, Bukstein O
chopharmacol (1998) 8:325–8. et al, Clonazepam as an aug-
74 Khanna S, Gangadhar BN, Sinha menting agent in the treatment of
V et al, Electroconvulsive therapy childhood-onset obsessive com-
in obsessive-compulsive disor- pulsive disorder, J Am Acad
der, Convuls Ther (1988) 4: Child Adolesc Psych (1994) 33:
314–20. 792–4.
75 Greenberg BD, George MS, Mar- 80 Fitzgerald KD, Stewart CM, Tawile
tin DJ et al, Effect of prefrontal V et al, Risperidone augmentation
repetitive transcranial magnetic of serotonin reuptake inhibitor
stimulation in obsessive compul- treatment of pediatric obsessive
sive disorder: a preliminary study, compulsive disorder, J Child Ado-
Am J Psychiatry (1997) 154: lesc Psychopharmacol (1999)
687–9. 9:115–23.
12
Obsessive compulsive disorder in children
and adolescents
Martine F Flament and David Cohen
Despite early descriptions of typical cases of obsessive compulsive dis-

order (OCD) in children, it was believed until recently that the disorder
was rare in young people. Ritualistic and compulsive-like activity was
considered to be part of the normal development of the behavioural
repertoire. The first systematic evidence of obsessive compulsive symp-
toms occurring at an early age came from retrospective studies with
adult OCD patients, suggesting that in 30% to 50% their disorder began
during childhood or adolescence.1,2 Epidemiological data subsequently
showed that OCD was far more prevalent among adolescents than previ-
ously thought. A number of systematic studies conducted on children
and adolescents with OCD, both in clinical settings and in the commun-
ity, have greatly increased our knowledge of the disorder in its early
stage. They have shown that, in contrast to other forms of psychopathol-
ogy, the specific features of OCD are essentially identical in children,
adolescents and adults. With a tremendous growth of interest and
research on childhood-onset OCD, significant advances have occurred
regarding phenomenology, epidemiology, genetics, neurophysiology,
pathogenesis and treatment of the disorder.
Clinical features
The clinical presentation of OCD during childhood and adolescent years

has been documented in various countries and various cultures, with
large clinical series reported from the USA,3 Japan,4 India,5 Israel,6 Den-
mark7 and Spain.8 In clinical samples, as in community-based samples,9
obsessions most commonly concern fear of dirt or germs, harm coming
to self or a loved one, symmetry or scrupulous religiosity, and the most
frequent presenting rituals include washing, repeating, checking, touch-
ing, ordering, counting and hoarding. Typically, children and adolescents
with OCD experience multiple obsessions and compulsions, whose
nature may change over time. Generally, compulsions are carried out to
153
dispel anxiety and/or in response to an obsession (e.g. to ward off harm

to someone). Some of the obsessions and rituals involve an internal
sense that ‘it does not feel right’ until the thought or action is completed.
No significant age-related trends have been found for either the number
or the type of symptoms, except that patients with very early onset tend
to have more compulsions than obsessions.10
Onset of OCD in children and adolescents may be acute or gradual.
Reports of the mean age at onset in referred subjects have ranged from
9.0 years11 to 11.6 years,4 and it was 12.8 years in a community study.9 In
community-based samples of adolescents with OCD there are approxi-
mately equal numbers of boys and girls, whereas in most studies of
referred children and adolescents boys outnumber girls 2 : 1. Overrepre-
sentation of boys in clinical samples may reflect a greater severity of the
disorder and an earlier age of onset than in girls.12
It has been consistently observed, in both clinical and community stud-
ies, that childhood OCD is frequently accompanied by other symptoms,
with an overall lifetime comorbidity as high as 75%.13 Mood and anxiety
disorders are the most common comorbid conditions, with prevalence
ranging across studies from 20% to 73%,14,15 and from 26% to 70%,3,15
respectively. Anorexia nervosa has been reported in 8% of OCD adoles-
cents;8 conversely, OCD has been found in 3% to 66% of girls with
anorexia nervosa.16 Of particular clinical importance is the high rate of
comorbid tic disorders, including Tourette’s disorder, which have been
reported in 17% to 40% of referred OCD patients,8,15 and in 25% of a
community-derived sample.17
Although findings regarding the significance of potential subtypes of
OCD remain to be confirmed, some authors have suggested that the dis-
tinction between ‘tic-related OCD’ and ‘non-tic-related OCD’, or between
early (prepubertal) and later (pubertal) onset, may be a useful one.18
Epidemiology
In adolescents, epidemiological studies using strict diagnostic criteria

and structured clinical interviews have been conducted in several parts
of the world, estimating the prevalence of OCD between 1% and 4%.19 In
the largest study, conducted in a US population of 5596 high-school stu-
dents,9 the current prevalence of OCD in adolescents was 1 (± 0.5)%,
and its lifetime prevalence 1.9 (± 0.7)%. The study showed that the disor-
der was clearly underdiagnosed and undertreated in this age group:
none of the cases identified had been previously diagnosed, and only
20% had ever been treated for comorbid psychological problems. In a
later study examining 562 consecutive inductees into the Israeli army, the
point prevalence of OCD was 3.6 (± 0.7)%.17 Of note was the high pro-
portion of subjects with obsessions only (50%), potentially less disruptive
Children and adolescents 155
of everyday functioning. If the prevalence of OCD was estimated exclud-

ing individuals who only had obsessions, the point prevalence dropped
to 1.8%. In two longitudinal studies following cohorts of children in the
community up to the age of 18 years, one from the USA found a lifetime
prevalence for OCD of 2.1%,20 and the other from New Zealand an over-
all 1-year prevalence of 4%, but only 1.2% when subjects with obses-
sions only were excluded.21 Thus, it appears that OCD might be as
frequent in adolescents as it is in adults.
There has been no community study on the prevalence of OCD during
childhood, but estimates of the frequency of OCD in clinical samples of
children range from 1.3% to 5%.18 They suggest that many youngsters
with OCD still do not come to clinical attention.
Pathogenesis
Although a variety of biological causes for OCD have been proposed

since 1860,22 modern neurobiological theories began with clinical studies
showing that clomipramine and other serotonin reuptake inhibitors had a
unique efficacy in treating OCD. In children and adolescents, a few stud-
ies have provided evidence of the involvement of the serotonergic sys-
tem in the pathophysiology of the disorder: there have been reports of
decreased density of the platelet serotonin transporter in children and
adolescents with OCD, but not in those with Tourette’s disorder,23,24 and
another study showed an increase in central serotonin turnover in chil-
dren and adolescents with OCD, compared with children and adoles-
cents with disruptive behaviour disorder.25
Several family studies have shown that OCD is much more frequent
among relatives of individuals with the disorder than would be expected
from estimated occurrence rates for the general population. Lenane et al,
interviewing first-degree relatives of 46 children and adolescents with
OCD, found that 25% of the fathers and 9% of the mothers had OCD, and
that the age-corrected risk for OCD and subthreshold OCD combined for
all first-degree relatives was 35%.26 Pauls et al reported that the prevalence
rates of OCD and tic disorders were significantly greater among the first-
degree relatives of 100 probands with OCD (10.3% and 4.6%, respec-
tively) than among relatives of psychiatrically unaffected subjects (1.9%
and 1.0%); interestingly, there was a two-fold increased risk for OCD and a
four-fold increased risk for subthreshold OCD in relatives of probands with
early onset (⭐18 years) of OCD, compared with those with a later onset.27
Data from neuroimaging studies have brought definite evidence of
morphological and/or functional abnormalities associated with at least
some forms of OCD. One computerized tomography study found signifi-
cantly smaller caudate volumes in young men with childhood-onset OCD
compared with controls,28 and one magnetic resonance morphologic
study reported that children with OCD had significantly larger anterior
cingulate gyri than did controls.29 Studies using functional neuroimaging
have tended to demonstrate metabolic abnormalities in the circuits
involving orbitofrontal/cingulate cortex and the basal ganglia.30 Further-
more, five of seven studies comparing brain functioning in OCD patients
before and after successful pharmacological or psychological therapy
demonstrated reduction of the hypermetabolism of the frontal lobes fol-
lowing treatment. One of these studies was conducted before and after
pharmacological treatment in childhood-onset OCD patients.31,32
Autoimmune factors have also been implicated in the possible patho-
genesis of OCD. Two independent groups of investigators demonstrated a
strong association between acute-onset OCD and Sydenham’s chorea, a
childhood movement disorder associated with rheumatic fever, which is
thought to result from an antineuronal antibody-mediated response to
group A ␤-haemolytic streptococcus (GABHS) directed at portions of the
basal ganglia, in genetically vulnerable individuals.33,34 Even in the absence
of the neurological symptoms of Sydenham’s chorea, post-streptococcal
cases of childhood-onset OCD, tics and/or other neuropsychiatric symp-
toms have been described under the acronym of PANDAS (Paediatric
Autoimmune Neuropsychiatric Disorders Associated with Streptococcal
infections).35 These findings of a probable autoimmune basis for OCD led
Swedo and colleagues to successfully apply immunomodulatory treat-
ments in children with severe, infection-triggered exacerbations of OCD or
tic disorders.36 However, the first double-blind attempt to demonstrate the
efficacy of penicillin prophylaxis in preventing tic or obsessive compulsive
symptoms exacerbation in PANDAS failed to do so, because of inability to
achieve an acceptable level of streptococcal prophylaxis.37
Treatment
The treatment of OCD has changed dramatically since the 1980s, with
two approaches systematically assessed and empirically shown to ame-
liorate the core symptoms of the disorder in children and adolescents:
pharmacological treatment with agents that are potent serotonin reuptake
inhibitors, and specific cognitive behavioural treatment.
Psychopharmacological treatment
Several randomized, controlled clinical trials and some additional open
studies have been conducted in children and adolescents with OCD,
demonstrating (like many similar studies in adult patients) the selective
and unique efficacy of serotonin reuptake inhibitors in the short-term
treatment of the disorder. The design and main results of these studies
are summarized in Table 12.1.
Table 12.1 Pharmacological treatment studies of OCD in children and adolescents.
Study (year) N (age) Drug (daily dose) Improvement on active
Duration of treatment Study design drug across measures (%)
Flament et al (1985)38 19 (6–18 yr) Clomipramine (mean: 141 mg) 22–44

5 weeks vs placebo
Leonard et al (1989)40 47 (7–19 yr) Clomipramine (mean:150 mg) 19–29

5 weeks vs desipramine
DeVeaugh-Geiss et al 60 (10–17 yr) Clomipramine (75–200 mg) 34–37

(1992)39 8 weeks vs placebo
Riddle et al (1992)42 14 (8–15 yr) Fluoxetine (20 mg) 33–44

8 weeks vs placebo
Apter et al (1994)43 14 (13–18 yr) Fluvoxamine (100–300 mg) 28

8 weeks open study
Thomsen (1997)44 23 (9–18 yr) Citalopram (mean: 37 mg) 20–29

10 weeks open study
March et al (1998)46 187 (6–17 yr) Sertraline (mean: 167 mg) 21–28
12 weeks vs placebo
Rosenberg et al (1999)45 20 (8–17 yr) Paroxetine (mean: 41 mg) 28

12 weeks open study
Clomipramine was the first known antiobsessional agent. Its efficacy in

children and adolescents with OCD has been demonstrated in two placebo-
controlled studies,38,39 and in one study comparing it with desipramine.40
Moderate or marked improvement with clomipramine (at doses ranging
from 75 mg to 200 mg per day) was apparent by 5 weeks of treatment in
about 75% of subjects; this was independent of the presence of depressive
symptoms at baseline. In one study, improvement of obsessive compulsive
symptoms was closely correlated with pretreatment platelet serotonin con-
centration, and with the decrease of this measure during treatment.41 Fluox-
etine was investigated in a small placebo-controlled study,42 and open label
trials have been published for fluvoxamine,43 citalopram,44 and paroxetine.45
The largest controlled study completed to date is a multicentre placebo-
controlled trial of sertraline, in which significant differences between sertra-
line and placebo emerged at week 3 and persisted for the duration of the
study.46 The degree of symptomatic improvement with the selective sero-
tonin reuptake inhibitors (SSRIs) is comparable to that observed in previous
trials with clomipramine (Table 12.1).
The secondary effects of clomipramine include dry mouth, somno-
lence, dizziness, tremor, headache, constipation, stomach discomfort,
sweating, insomnia, possible tachycardia and prolongation of the QT
interval on electrocardiography (ECG); baseline and periodic ECG moni-
toring is recommended.18 Published studies suggest that the SSRIs are
safe and well tolerated in children and adolescents. Although there are
differences between these drugs, the most commonly described side
effects include nausea, headache, tremor, gastrointestinal complaints,
drowsiness, insomnia, akathisia, disinhibition, agitation and hypomania.
Systematic dose response data are not available for children, but side
effects generally appear dose-dependent. It is therefore recommended
to start an SSRI with a low dosage that is increased slowly up to the mini-
mum daily dose found effective in adult patients (fluoxetine 20 mg, sertra-
line 50 mg, paroxetine 40 mg, citalopram 20 mg; no fixed-doses studies
for fluvoxamine), although much higher doses have been used in pub-
lished studies (Table 12.1).
For children and adolescents with OCD and comorbid tic disorder,
SSRIs alone might have little antiobsessional effect, and there are reports
suggesting that these agents, especially at higher doses, may exacer-
bate or even induce tics in some patients.13 In such cases, the efficacy of
a combined treatment with an SSRI and a dopamine antagonist has been
demonstrated in adults, but still needs to be confirmed in younger
patients.
The optimal duration of maintenance treatment is unclear, since
relapses are frequent when medication is discontinued.47 Antiobsessional
medication should be maintained for at least 12–18 months after a satis-
factory clinical response has been obtained. Once the decision is made
to attempt reduction or discontinuation, the tapering should be gradual.
Cognitive behavioural treatment

Cognitive behavioural treatment (CBT) is regarded as the psychological
treatment of choice for children and adolescents with OCD. In contrast to
medication, where relapse is common when treatment is withdrawn, CBT
has been shown to be a more durable treatment, although booster ses-
sions may be required from time to time. Treatment generally involves a
three-stage approach, consisting of information gathering, therapist-
assisted graded exposure with response prevention, and homework
assignments.48 Interventions for children with predominantly internalizing
symptoms also include relaxation and cognitive training. The family
needs to be involved in the treatment to a varying extent according to
individual situations. This therapy usually involves 13–20 weekly individ-
ual or family sessions and homework assignments. Partial or non-respon-
ders may require more frequent visits and therapist-assisted training at
home.
Three open studies (Table 12.2) have shown beneficial effects of CBT,
alone or in combination with pharmacotherapy, in groups of 14–15 chil-
dren and adolescents with OCD: following treatment, symptoms were
relieved entirely or reduced to a mildly incapacitating level in 50% to 86%
of cases.49–51 In a randomized trial comparing CBT and clomipramine,52
CBT produced stronger therapeutic changes than clomipramine after 12
weeks, and, after another 12 weeks, five of the nine initial non-responders
showed significant changes with a combination of both treatment
regimens.
Other therapeutic approaches

Although some uncontrolled case studies have found psychodynamic
psychotherapy useful in treating juvenile OCD,53,54 the effectiveness of
psychotherapy alone – apart from exposure techniques – on obsessive
and compulsive symptoms has yet to be systematically explored. Never-
theless, traditional psychotherapeutic approaches may help children and
adolescents address intrapsychic conflicts that affect or result from their
illness.
Family psychopathology is neither necessary nor sufficient for the
onset of OCD. Nonetheless, families affect and are affected by the disor-
der. Work with families on how to manage the child’s symptom, cope with
the stress and family disruption that often accompanies OCD, and partic-
ipate effectively in behavioural or pharmacological treatment, is
essential.55 Family support groups and patient advocacy groups, now
available in many countries, can also provide valuable help and support.
In cases of severe OCD, there is empirical evidence that milieu therapy
in inpatient settings may be a useful resource.49,53
Table 12.2 Cognitive behavioural treatment (CBT) studies of OCD in children and adolescents.
Study (year) N (age) Study design Short-term Long-term
Duration of treatment improvement improvement
Bolton et al (1983)49 15 (12–18 yr) Open trial CBT 7 asymptomatic 9 months to 4 years:
1–48 months ± drug or other treatment 6 much improved 11/14 improved
March et al (1994)50 15 (8–18 yr) Open trial CBT 6 asymptomatic 18 months:

22 weeks ± drug or other treatment 3 much improved 9/15 improved
Franklin et al (1998)51 14 (10–17 yr) Open trial CBT 12 responders 9 months:

1–4 months ± drug or other treatment (≥50% decrease in 10/12 improved
OC symptoms)
De Haan et al (1998)52 22 (8–18 yr) Randomised trial 8/12 responders (≥30% Not reported
12 weeks CBT (n =12) vs decrease in OC symptoms)
clomipramine (n =10) on CBT vs 5/10 responders
on clomipramine (p < 0.05)
Course and outcome

Several retrospective and prospective follow-up studies have demonstra-
ted the continuity of the diagnosis of OCD from childhood to adulthood:
when subjects are still symptomatic, the main diagnosis is almost invari-
ably OCD, although comorbid disorders, especially mood and/or anxiety
disorders, are frequent; evolution towards psychosis is rare.12 The spon-
taneous course is most often marked by a waxing and waning severity of
the disorder, whereas remissions under treatment may be followed by
relapses, even after long periods.
In the earliest follow-up studies, when no specific treatment was avail-
able, recovery rate in early adulthood ranged from 13%56 to 28%.9 By the
time patients had access to specific treatments with SSRIs and/or CBT,
recovery rates increased to 57–65%,57–59 although in some studies many
of the subjects symptom-free at follow-up were still taking medication.
Studies on the natural course of OCD and on the clinical response to
treatment have attempted to identify demographic or clinical features that
may influence outcome or course of illness – with mainly negative or
inconsistent results.12 Except for one short-term pharmacological study,
in which male subjects responded significantly better than did female
subjects,38 the initial treatment response could not be predicted by sex,
age of onset, duration or severity of illness, or type of symptoms. In a
prospective follow-up study, over 2–7 years, a poorer long-term outcome
was predicted by a higher obsessive compulsive symptom score after
the first 5 weeks of pharmacotherapy (but not at baseline), and by the
presence of a lifetime history of tic disorder or of a parental Axis I psychi-
atric diagnosis.57
Conclusion
Obsessive compulsive disorder is much more frequent in children and

adolescents than previously thought. Youths with OCD suffer from a wide
range of symptoms, including both obsessions and compulsions, that
may change over time, but all longitudinal studies clearly demonstrate
the continuity of the disorder from childhood to adulthood. Short-term and
longer follow-up studies gave definite evidence that two types of treat-
ment intervention can markedly improve the core symptoms of the disor-
der, and significantly reduce impairment from the condition. Cognitive
behavioural treatment may be the initial treatment of choice in milder
cases without significant comorbidity, whereas severity of obsessive
compulsive symptoms, presence of comorbid conditions, or insufficient
cognitive or emotional ability to cooperate in CBT, are indications for
pharmacological treatment with a serotonin reuptake inhibitor. The com-
bination treatment may be more effective than either alone, and CBT may
reduce the relapse rate in patients withdrawn from medication.

Although the currently available treatments may not be curative, most
children and adolescents given a correct diagnosis and an individually
targeted treatment may be substantially helped to resume a normal
developmental trajectory. However, more research is needed into the
basic neurobiological mechanisms in OCD, to improve understanding
and long-term outcome of what may prove to be an heterogeneous
disorder.
References
1 Black A, The natural history of Child Psychol Psychiat (1992)
obsessional neurosis. In: Beech 33:1025–37.
HR, ed., Obsessional States 9 Flament MF, Whitaker A,
(Methuen: London, 1974) Rapoport JL et al, Obsessive
2 Rasmussen SA, Eisen JL, Epi- compulsive disorder in adoles-
demiology of obsessive compul- cence: an epidemiological study,
sive disorder, J Clin Psychiatry J Am Acad Child Adolesc Psychi-
(1990) 51(2 suppl.):10–13. atry (1988) 27:764–71.
3 Swedo SE, Rapoport JL, Leonard 10 Rettew DC, Swedo SE, Leonard
H, Lenane M, Cheslow D, Obses- HL, Lenane M, Rapoport JL,
sive-compulsive disorder in chil- Obsessions and compulsions
dren and adolescents. Clinical across time in 79 children and
phenomenology of 70 consecu- adolescents with obsessive-com-
tive cases, Arch Gen Psychiatry pulsive disorder, J Am Acad
(1989) 46:335–40. Child Adolesc Psych (1992) 31:
4 Honjo S, Hirano C, Murase S et al, 1050–56.
Obsessive-compulsive symptoms 11 Riddle MA, Scahill L, King R et al,
in childhood and adolescence, Obsessive compulsive disorder in
Acta Psychiatr Scand (1989) children and adolescents: phe-
80:83–91. nomenology and family history, J
5 Khanna S, Srinath S, Childhood Am Acad Child Adolesc Psych
obsessive compulsive disorder. I. (1990) 29:766–72.
Psychopathology, Psychopathol- 12 Flament MF, Obsessive-compul-
ogy (1989) 32:47–54. sive disorder. In: Steinhausen HC,
6 Apter A, Tyano S, Obsessive Verhulst F, eds Risks and Out-
compulsive disorders in adoles- comes in Developmental Psy-
cence, J Adolesc (1988) 11: chopathology (Oxford University
183–94. Press: Oxford, 1999)
7 Thomsen PH, Obsessive-compul- 13 Flament MF, Cohen D, Child and
sive symptoms in children and adolescent obsessive compulsive
adolescents. A phenomenological disorder. In: Maj M, Sartorius N,
analysis of 61 Danish cases, Psy- eds, Obsessive-compulsive Dis-
chopathology (1991) 24:12–18. order. WPA Series Evidence and
Experience in Psychiatry Vol. 4
8 Toro J, Cervera M, Osjeo E,
(John Wiley & Sons Chichester,
Salamero M, Obsessive-compul-
2000; 147–83).
sive disorder in childhood and
adolescence: a clinical study, J 14 Flament MF, Koby E, Rapoport JL
et al, Childhood obsessive-com- 22 Rapoport JL, The neurobiology of

pulsive disorder: a prospective obsessive compulsive disorder,
follow-up study, J Child Psychol JAMA (1989) 260:2888–90.
Psychiat (1990) 31:363–80. 23 Weizman A, Mandel A, Barber Y
15 Geller DA, Biederman J, Griffin S, et al, Decreased platelet
Jones J, Lefkowitz TD, Comorbid- imipramine binding in Tourette
ity of obsessive-compulsive disor- syndrome children with obses-
der with disruptive behavior sive-compulsive disorder, Biol
disorders, J Am Acad Child Ado- Psychiatry (1992) 31:705–11.
lesc Psych (1996) 35:1637–46. 24 Sallee FR, Richman H, Beach K et
16 Godart N, Flament MF, Jeammet al, Platelet serotonin transporter in
P, Lecrubier Y, Eating disorders children and adolescents with
and anxiety disorders: comorbidity obsessive-compulsive disorder or
and chronology of appearance, Tourette’s syndrome, J Am Acad
Eur Psychiatry (2000) 15:38–45. Child Adolesc Psych (1996) 35:
1647–56.
17 Zohar AH, Ratzosin G, Pauls DL
et al, An epidemiological study of 25 Zahn TP, Kruesi MJP, Swedo SE
obsessive-compulsive disorder et al, Autonomic activity in relation
and related disorders in Israeli to cerebrospinal fluid neurochem-
adolescents, J Am Acad Child istry in obsessive and disruptive
Adolesc Psych (1992) 31: children and adolescents, Psy-
1057–61. chophysiology (1992) 33:731–9.
18 American Academy of Child and 26 Lenane MC, Swedo SE, Leonard
Adolescent Psychiatry, Practice H et al, Psychiatric disorders in
parameters for the assessment first degree relatives of children
and treatment of children and and adolescents with obsessive
adolescents with obsessive-com- compulsive disorder, J Am Acad
pulsive disorder, J Am Acad Child Adolesc Psych (1990) 29:
Child Adolesc Psych (1998) 407–12.
37(suppl 10):27–45S. 27 Pauls D, Alsobrook J, Goodman
19 Flament MF, Chabane N, Obses- W et al, A family study of obses-
sive-compulsive disorder and tics sive-compulsive disorder. Am J
in children and adolescents. In: Psychiatry (1995) 152:76–84.
Gelder M, Lopez-Ibor JJ, 28. Luxemberg J, Swedo S, Flament M
Andreasen NC, eds, The New et al, Neuroanatomical abnormali-
Oxford Textbook of Psychiatry, ties in obsessive-compulsive dis-
(Oxford University Press: Oxford, order detected with quantitative
2000; 1771–81). X-ray computed tomography, Am
20 Reinherz HZ, Giaconia RM, J Psychiatry (1988) 145:1089–93.
Lefkowitz ES, Pakiz B, Frost AK, 29 Rosenberg DR, Keshavan MS,
Prevalence of psychiatric disorders Toward a neurodevelopmental
in a community population of older model of obsessive-compulsive
adolescents, J Am Acad Child disorder, Biol Psychiatry (1998)
Adolesc Psych (1993) 32:369–77. 43:623–40.
21 Douglass HM, Moffitt TE, Dar R, 30 Cottraux J, Gérard D, Neuroimag-
McGee R, Silva P, Obsessive- ing and neuroanatomical issues
compulsive disorder in a birth in obsessive-cognitive disorder.
cohort of 18-year-olds: preva- In: Obsessive-compulsive Disor-
lence and predictors, J Am Acad der: Theory, Research, and Treat-
Child Adolesc Psych (1995) 34: ment Guilford Press: New York
1424–31. (1998): 154–80.
31 Swedo S, Shapiro M, Grady C et derman J et al, Clomipramine

al, Cerebral glucose metabolism hydrochloride in childhood and
in childhood obsessive-compul- adolescent obsessive-compulsive
sive disorder, Arch Gen Psychia- disorder: a multicenter trial, J Am
try (1989) 46:518–23. Acad Child Adolesc Psych (1992)
32. Swedo S, Pietrini P, Leonard H et 31:45–9.
al, Cerebral glucose metabolism 40 Leonard HL, Swedo SE, Rapoport
in childhood obsessive-compul- JL et al, Treatment of obsessive-
sive disorder: revisualization dur- compulsive disorder with
ing pharmacotherapy, Arch Gen clomipramine and desipramine in
Psychiatry (1992) 49:690–4. children and adolescents, Arch
33 Swedo SE, Rapoport JL, Cheslow Gen Psychiatry (1989) 46:
DL et al, High prevalence of 1088–92.
obsessive-compulsive symptoms 41 Flament MF, Rapoport JL, Murphy
in patients with Sydenham’s DL et al, Biochemical changes
chorea, Am J Psychiatry (1989) during clomipramine treatment of
146:246–9. childhood obsessive compulsive
34 Asbahr FR., Negrao AB, Gentil V disorder, Arch Gen Psychiatry
et al, Obsessive-compulsive and (1987) 44:219–25.
related symptoms in children and 42 Riddle MA, Scahill L, King RA et
adolescents with rheumatic fever al, Double-blind, crossover trial of
with and without chorea: a fluoxetine and placebo in children
prospective 6-month study, Am J and adolescents with obsessive-
Psychiatry (1998) 155:1122–4. compulsive disorder, J Am Acad
35 Swedo S, Leonard HL, Garvey M Child Adolesc Psych (1992)
et al, Pediatric autoimmune neu- 31:1062–9.
ropsychiatric disorders associ- 43 Apter A, Ratzoni G, King RA et al,
ated with streptococcal infections Fluvoxamine open-label treatment
(PANDAS): clinical description of of adolescent inpatients with
the first 50 cases, Am J Psychia- obsessive-compulsive disorder or
try (1998) 155:264–71. depression, J Am Acad Child
36 Perlmutter SJ, Leitman SF, Gar- Adolesc Psych (1994) 33:342–8.
vey MA et al, Therapeutic plasma 44. Thomsen PH, Child and adoles-
exchange and intravenous cent obssesive-compulsive disor-
immunoglobulin for obsessive- der treated with citalopram:
compulsive disorder and tic dis- findings from an open trial of 23
orders in childhood, Lancet cases, J Child Adolesc Psy-
(1999) 354:1153–8. chopharmacol (1997) 7:157–66.
37 Garvey MA, Perlmutter SJ, Allen 45 Rosenberg DR, Stewart CM,
AJ et al, A pilot study of penicillin Fitzgerald KD et al, Paroxetine
prophylaxis for neuropsychiatric open-label treatment of pediatric
exacerbations triggered by strep- outpatients with obsessive-com-
tococcal infections, Biol Psychia- pulsive disorder, J Am Acad
try (1999) 45:1564–71. Child Adolesc Psych (1999)
38 Flament MF, Rapoport JL, Berg 38:1180–5.
CJ et al, Clomipramine treatment 46 March JS, Biederman J, Wolkow
of childhood obsessive-compul- R et al, Sertraline in children and
sive disorder. A double-blind con- adolescents with obsessive-com-
trolled study, Arch Gen Psychiatry pulsive disorder: a multicenter
(1985) 42:977–83. randomized controlled trial, JAMA
39 DeVeaugh-Geiss J, Moroz G, Bie- (1998) 280:1752–6.
47 Leonard HL, Swedo SE, Lenane 53 Apter A, Bernhout E, Tyano S,

MC et al, A double-blind Severe obsessive compulsive dis-
desipramine substitution during order in adolescence: a report of
long-term clomipramine treatment eight cases, J Adolesc (1984)
in children and adolescents with 7:349–58.
obsessive-compulsive disorder, 54 Target M, Fonagy P, Efficacy of
Arch Gen Psychiatry (1991) psychoanalysis for children with
48:922–7. emotional disorders, J Am Acad
48 March JS, Cognitive-behavioral Child Adolesc Psych (1994)
psychotherapy for children and 33:361–71.
adolescents with OCD: a review 55 Lenane M, Family therapy for chil-
and recommendations for treat- dren with obsessive-compulsive
ment, J Am Acad Child Adolesc disorder. In: Current Treatments
Psych (1995) 34:7–18. of Obsessive-compulsive Disor-
49 Bolton D, Collins S, Steinberg D, der – Clinical Practice Washing-
The treatment of obsessive-com- ton DC, Pato M, Zohar M, eds,
pulsive disorder in adolescence. American Psychiatric Association:
A report of fifteen cases, Br J Psy- 103–13.
chiatry (1983) 142:456–64. 56 Warren W, Some relationships
50 March JS, Mulle K, Herbel B, between the psychiatry of chil-
Behavioral psychotherapy for dren and adults, J Ment Sci
children and adolescents with (1960) 106:815–26.
obsessive-compulsive disorder: 57 Leonard HL, Swedo SE, Lenane
an open trial of a new protocol- MC et al, A 2- to 7-year follow-up
driven treatment package, J Am study of 54 obsessive-compulsive
Acad Child Adolesc Psych (1994) children and adolescents, Arch
33:333–41. Gen Psychiatry (1993) 50:429–39.
51 Franklin ME, Kozak MJ, Cashman 58 Bolton D, Luckie M, Steinberg D,
L et al, Cognitive-behavioral treat- Long-term course of obsessive-
ment of pediatric obsessive com- compulsive disorder treated in
pulsive disorder: an open clinical adolescence, J Am Acad Child
trial. J Am Acad Child Adolesc Adolesc Psych (1995) 34:
Psych (1998) 37:412–19. 1441–50.
52 De Haan E, Hoogduin KA, Buite- 59 Thomsen PH, Mikkelsen HU,
laar JK, Keijsers G, Behavior ther- Obsessive-compulsive disorder in
apy versus clomipramine for the children and adolescents: predic-
treatment of obsessive-compul- tors in childhood for long-term
sive disorder in children and ado- phenomenological course, Acta
lescents, J Am Acad Child Psychiatr Scand (1995) 92:255–9.
Adolesc Psych (1998), 37:1022–9.
13
An integrated approach to the treatment of
OCD
Dan J Stein, Naomi Fineberg and Soraya Seedat
Obsessive compulsive disorder (OCD) is, arguably, the psychiatric disor-

der that best exemplifies an integrated ‘brain–mind’ approach to the
understanding of psychopathology. Previous chapters have covered
aspects of the psychobiology of OCD; in particular, questions about the
neuroanatomical, neurochemical and cognitive mechanisms mediating
obsessional and compulsive symptoms have been explored. In this
chapter we use this range of findings to provide a framework for an inte-
grated approach to the treatment of OCD.
What is the core psychobiological deficit in OCD?
An integrated approach to the treatment of OCD would ideally rest on the

basis of a clear understanding of the nature of the core psychobiological
deficit underlying the disorder. Despite significant neurobiological
advances in the field, defining a core psychobiological deficit in OCD
remains an ambitious undertaking. As a first step towards this goal, we
would tentatively suggest that the fundamental deficiency in OCD
revolves around faults in the selection, maintenance and termination of
‘procedural strategies’, particularly (but not exclusively) those involving
harm assessment.
Cortico–striatal–thalamic–cortical circuits and OCD

This characterization requires some unpacking. We can begin by recall-
ing that the bulk of current evidence – neuropsychological, neuroimag-
ing, neuroimmunological, and neurosurgical – emphasizes the role of
cortico–striatal–thalamic–cortical (CSTC) dysfunction in OCD.1,2 the
immediate question, then, is what is the normal role of these circuits? The
answer might be a clue to the nature of the core dysfunction in OCD.
It is widely believed that CSTC circuits play a role in organizing motor
and cognitive procedural strategies.3–5 Take, for example, the procedure
167
for riding a bicycle. When we initially learn to ride, the effort requires a
good deal of conscious concentration. However, over time, the
brain–mind encodes a ‘bicycling procedure’ – this procedure is enacted
non-consciously and automatically – under the direction of the striatum.
Even when we lose our explicit memories of learning to ride a bicycle, our
implicit knowledge of how to ride remains (this kind of dissociation has
been documented, for example, in studies of dementia).
There is evidence suggesting that the neural mechanisms underlying
procedural knowledge are disrupted in OCD. For example, when under-
taking an implicit cognition task during functional brain imaging, normal
controls demonstrated activation of CSTC circuits (especially striatum),
but OCD patients showed a pathological activation of temporal regions
instead.6 Of course, OCD is not a dysfunction in bicycling; rather, OCD
typically involves procedures that involve the assessment of harm. Thus,
although OCD has been suggested to be a disorder of grooming (and
some associated symptoms, such as tics, are primarily motoric), in
patients with cleaning rituals there are invariably concerns about the
harm of contamination.
The fact that the orbitofrontal cortex rather than the amygdala is pre-
dominantly activated in brain imaging studies of OCD suggests that the
stimuli that generate anxiety for the OCD sufferer originate internally
rather than externally. In contrast, in post-traumatic stress disorder
(PTSD) a loud noise may stimulate thalamo–amygdaloid activation and
produce an implicit, automatic fear response (startle reaction, etc.). It is
postulated that in OCD, once a trigger – say a speck of dirt – has been
noticed, an internal cognitive process, perhaps comprising disrupted or
inefficient striatal processing, results in the exaggeration of its potential
harmful consequences.
Core deficit vs compensatory dysfunctions

Although it is possible that increased orbitofrontal activation represents a
primary lesion in OCD, there is increasing support for the idea that it is
instead a compensatory response. In this view, orbitofrontal activation
represents a compensatory reaction to dysfunction in subcortical struc-
tures, along the lines of a ‘natural defence’ against obsessional anxiety.
Thus, increased activity in the orbitofrontal cortex may be an attempt to
suppress striatally mediated harm exaggeration in OCD. It has been sug-
gested that one of the roles of treatment may be to bolster this ‘natural
defence’ mechanism.
The finding that OCD patients with low orbitofrontal activity prior to
treatment are less likely to respond to medication is in line with this
hypothesis.7 It is as if there is not enough capacity in the system for ade-
quate compensation to be achieved. Similarly, it is interesting that the
behavioural exacerbation of OCD by sumatriptan, a specific agonist of
Integrated approach to treatment 169
the terminal autoreceptor (5-HT1D) appears associated with decreased

activity in areas of prefrontal cortex,8 perhaps suggesting that the level of
activity in the compensatory circuitry has been turned down by the drug.
Neurochemical theories and OCD
The neurochemical abnormalities found in OCD appear consistent with a

hypothesis involving striatal dysfunction and abnormalities in procedures
involving harm assessment, with orbitofrontal activation as a compen-
satory phenomenon. Both the striatum and the frontal cortex receive a
rich innervation from serotonergic neurons, and a number of studies have
begun to explore the interaction between neuroanatomical and neuro-
chemical systems in OCD.8,9
It is notable that certain serotonergic systems appear underactive in
OCD10,11 as well as in impulsivity11 (e.g. blunted prolactin response to the
serotonergic agonist methyl-chlorophenylpiperazine (mCPP). The cogni-
tive process whereby a speck of dirt triggers exaggerated fear of harm
(by contamination) and sets off handwashing compulsions may well
reflect striatal serotonergic hypofunction. Conversely, there is also evi-
dence of hyperserotonergic function in OCD (e.g. enhanced growth hor-
mone responses to L-tryptophan and D-fenfluramine,12,13 symptom
exacerbation after mCPP),10,14 and this may represent prefrontal compen-
satory mechanisms at work.
This view of underlying deficit and secondary compensation in OCD
provides a speculative way of tying together a range of neuroanatomical
and neurochemical findings. But does it make sense in terms of our clini-
cal understanding of the symptomatology and experience of suffering
from OCD?
Psychodynamic theories and OCD
One of the most convincing descriptions of the phenomenology of OCD

turns out to be that of Freud. Indeed, Freud’s understanding of obses-
sional neurosis provides a cornerstone for psychodynamic theory, and is
consistent with much modern thinking about the operation of an uncon-
scious. For Freud, at the heart of obsessional neurosis are unconscious
aggressive instincts.15 Unacceptable urges, particularly hostile urges, are
admitted into awareness because of incomplete repression, necessitat-
ing defensive responses in the form of compulsive rituals to reduce guilt
and anxiety.
This formulation is redolent of the psychobiological characterization
provided in the previous section. In OCD there may be a non-conscious,
striatally mediated impulsive/disinhibited process. This results in frontally
mediated compensatory attempts to switch this process off. A range of

more recent data support a link between OCD and behavioural disinhibi-
tion. Epidemiological data indicate that OCD is frequently associated with
a history of childhood impulsivity and aggression.16 Furthermore, in clini-
cal settings, individuals with OCD often demonstrate a degree of
impulsive-aggression,11 which, given their harm avoidance, is counter-
intuitively high.
More cognitive models: the role of doubt
So far we have concentrated on the central theme of harm assessment in

OCD. Other authors, such as Tallis,17 have drawn attention to the role of
doubt in this disorder. According to Freud, doubt leads the patient to
uncertainty about his protective measures, and to his continual repetition
of them in order to banish that uncertainty. It is as though obsessional
patients have lost the ability to register they have done something, or
even to ‘know if they know something’.18
It has been suggested that dysfunction of CSTC circuits may interfere
with the normal verification of the successful completion of preventative
or reparative behaviours, leading to compulsive repetition of the behav-
iours until appropriate information processing is accomplished.19 Just
how the compulsion eventually stops is not clear; perhaps the energy
dissipates a little like that of a tuning fork.
An integrated approach to treatment
If the core psychobiological dysfunction in OCD revolves around striatally

mediated problems in the selection, maintenance and termination of pro-
cedural strategies, how might we approach treatment?
First, serotonergic medication can be used to optimize striatal function,
either by direct action at receptors in the striatum, or by augmenting
orbitostriatal compensatory mechanisms as described above. Where stri-
atal damage is more extensive, dopamine blockers may provide an addi-
tional mechanism for increased serotonergic neuronal activity, since
dopaminergic neurons act to inhibit striatal serotonergic neurons.20
Second, cognitive-behavioural techniques can be used to regulate stri-
atal function. For some reason, exposure to feared stimuli, like pharma-
cotherapy, ultimately results in optimization of the CSTC circuits. Baxter’s
elegant work showing comparable effects of a selective serotonin reup-
take inhibitor and behavioural therapy on the functional neuroanatomy of
OCD, remains a key finding propelling forward the idea of an integrated
brain–mind approach to OCD.21
Third, there may be a range of preventative interventions that can be
applied, early in life, to protect the striatum. The basal ganglia are partic-
ularly vulnerable to neonatal hypoxaemia, and preventing this is therefore
important. The finding that childhood emotional deprivation is associated
with neuroanatomical abnormalities in the striatum provides an even
more challenging area for therapeutic intervention.22
Finally, autoimmune processes in the aftermath of streptococcal infec-
tion may also result in striatal damage.23 It will be interesting to see
whether prophylactic measures including aggressive early diagnosis and
intervention with antibiotics are ultimately able to have a positive impact
on the occurrence and course of Paediatric Autoimmune Neuropsychi-
atric Disorders Associated with Streptococcus (PANDAS).24
Are integrated treatments more effective in OCD?

We know that serotonin reuptake inhibitors (SRIs) and behaviour therapy
are individually effective in OCD, and it would therefore seem likely that
the combination of both treatments would provide even better efficacy. In
fact, there have been few studies looking at this area, and the evidence
to date remains incomplete.25 Meta-analyses, such as that by Picinelli et
al,26 have not succeeded in addressing the question of relative efficacy of
interventions, partly because this kind of statistical approach cannot ade-
quately correct for the changes that have occurred between individual tri-
als over the years, such as rising placebo response rates during the
1990s and the greater numbers of treatment-resistant and atypical
patients entering later medication trials. Head-to-head comparisons of
the effects of combination treatment versus drug or behavioural
monotherapy are preferable, and it is regrettable that so few properly
controlled studies have been performed.
Early influential studies by Marks and colleagues were the first to
address the question of how best to sequence and combine pharmaco-
therapy and psychotherapy in OCD.27,28 Their first study suggested that
the addition of clomipramine to behaviour therapy enhanced compliance
and produced a more favourable outcome.27 These results were echoed
in a second study, where the addition of clomipramine to exposure ther-
apy produced a greater level of improvement.28 Unfortunately these stud-
ies are limited by a number of methodological problems, including the
use of small sample sizes.
A study by Kozac, Liebowitz and Foa (personal communication) inves-
tigating the clinical effectiveness of cognitive-behavioural psychotherapy,
pharmacotherapy and combination therapy in a large group of patients
was initiated, but did not develop into a full trial. However, two small stud-
ies by Cottraux et al and Hohagen et al have been reported in full.29,30
Both studies compared fluvoxamine plus behaviour therapy with placebo
plus behaviour therapy, and, in spite of small numbers, demonstrated
superior efficacy for the combination over exposure monotherapy for up
to 6 months. There was no drug monotherapy arm in one of the studies.30

The study by Cottraux et al was unable to show a significant advantage
for combined drug and exposure compared with fluvoxamine, even
though the drug was given in combination with antiexposure (which
should have had an adverse effect), but the study was probably under-
powered (n ⫽ 40), and the authors themselves advocated further, larger
studies.29
All in all, it may be concluded that there is benefit to be gained by
adding drug treatment to exposure therapy, but it is rather less clear
whether combining drug treatment with exposure is any more effective
than drug treatment given alone. Optimistic claims from uncontrolled
case series that cognitive-behaviour therapy prevents relapse if medica-
tion is prematurely discontinued (e.g. March et al),31 although intuitively
persuasive, need to be explored further under properly controlled
conditions.
An integrated approach in practice

So far this chapter has been rather theoretical. How does an integrated
approach work in practice?
The first step of treatment is a comprehensive psychiatric and medical
history and examination. Particular symptoms in OCD (such as tics) and
comorbid disorders (such as depression) may well influence the choice
of intervention. Evaluation of OCD symptoms with a scale such as the
Yale–Brown Obsessive Compulsive Scale (see Appendix 1, p. 183) is
useful in determining treatment targets. During these initial interactions
with the patient, conveying an empathic appreciation of the experience of
OCD is crucial for strengthening the clinician–patient relationship, and
this kind of effect may even have contributed to the efficacy of placebo in
recent clinical trials. Patients are often relieved to realize from the direc-
tion of the clinician’s questions that other patients also suffer from
intensely embarrassing symptoms (such as intrusive sexual obsessions).
Once the patient has been appropriately evaluated and diagnosed it is
important to begin a process of psychoeducation. In many ways, this is
the first step of cognitive-behavioural treatment. It is useful to begin by
asking patients for their ‘explanatory model’ of OCD – what are their
ideas about the cause of their symptoms?32 Often people misconstrue
symptoms as reflecting unconscious guilt, or as pointing towards a hid-
den personality fault. The shame that is associated with the experience of
OCD (e.g. feeling incompetent for being unable to control an ego-
dystonic compulsion) is presumably one of the reasons for the long lag
time between first experiencing OCD symptoms and seeking treatment.33
The clinician can present an alternative view of OCD as a striatal ‘false
alarm’ (as outlined in different words above) and then negotiate with the
patient to try to achieve a shared understanding and treatment plan.
The use of psychoeducation raises the question of consumer advo-

cacy; this would seem increasingly relevant to an integrated approach to
the treatment of OCD. Modern media allow for rapid communication of
ideas, and for bringing together clinicians and consumers electronically.
Stigmatization of mental illness can be addressed by providing appropri-
ate information, referral to support groups, etc. Virtual support groups
can also be immensely useful for people with OCD.34 Given the early
onset of OCD symptoms, there would seem to be a need to target infor-
mation about OCD and other psychiatric disorders to youngsters and to
professionals such as teachers who are most often in contact with this
population.
Once treatment itself begins, either medication or cognitive-
behavioural therapy can be chosen, depending on a range of factors
including symptom severity, comorbid illness (e.g. depression), and
patient choice. (We use the term ‘cognitive-behavioural therapy’ as cog-
nitive interventions may also have a role in the treatment of OCD,
although the majority of evidence for the efficacy of psychotherapy in
OCD has focused on the value of exposure per se). Despite the relatively
limited database discussed earlier, most clinicians conservatively advo-
cate combined pharmacotherapy and psychotherapy, if available, for the
majority of OCD patients. If medication is to be discontinued, it would
seem wise to do this gradually over a period of months, and to stress
again the principles of exposure therapy during this time.
Drug treatment is generally available and can be monitored by a pri-
mary care practitioner, except where unusually high doses of medication
or augmentation strategies are employed. Cognitive-behavioural therapy
for OCD is generally less accessible and usually requires referral to a
specialist centre, where there are often long waiting lists for treatment.
However, the psychotherapy component of exposure therapy is not diffi-
cult to learn, and can be taught to a range of mental-health professionals.
Indeed, there seems to be a demand from community psychiatric nurses
to learn these skills.
Next, it is useful to incorporate the family and significant others into the
treatment plan. It is important, for example, to assess the adverse effects
of the patient’s symptoms on family function.35 Furthermore, behavioural
techniques may not be effective when the family works (sometimes in
good faith) to prevent exposure. For example, when a patient with conta-
mination concerns has an equally fastidious spouse, there is often mutual
reinforcement to exclude exposure, and the couple must therefore be
treated together.
In refractory patients, partial or full hospitalization may be a useful
option for ensuring that both optimal pharmacotherapy and psychother-
apy are given.36 Referral to a specialist unit for OCD where both forms of
treatment (as well as expertise in neurosurgery) are available should
be considered in patients who have failed initial pharmacotherapy,
psychotherapy, or combined treatments. Fortunately, however, the major-

ity of people with OCD can be treated on an outpatient basis and will
respond to simple combinations of psychoeducation, an SRI and expo-
sure therapy.
Conclusion
Although much remains to be understood about the neurobiology of

OCD, there is a convergence on certain hypotheses, and striatal dys-
function seems particularly important. Remarkably, both psychotherapy
and pharmacotherapy result in normalization of striatal function. Taken
together, this means that OCD provides an extraordinarily powerful
model of a contemporary approach to the brain–mind, to psychopathol-
ogy, and to treatment. In the clinical setting it is useful to be able to edu-
cate the patient that the ‘false alarm’ in their brain–mind can be reset
through a combination of pharmacotherapy and exposure. For
researchers, determining the precise mechanisms through which these
interventions operate remains an exciting challenge.
References
1 Rauch SL, Baxter LR, Neuroimag- Movement Disorders (Raven
ing in obsessive-compulsive dis- Press: New York, 1995).
order and related disorders. In: 6 Rauch SL, Savage CR, Alpert NM
Jenicke MA, Baer L, Minichiello et al, Probing striatal function in
WE (eds) Obsessive-Compulsive obsessive compulsive disorder: a
Disorders: Practice Management, PET study of implicit sequence
(3rd edn) (Mosby: St Louis, learning, J Neuropsychiatry
1998). (1997) 9:568–73.
2 Stein DJ, Goodman WK, Rauch
7 Swedo SE, Pietrini P, Leonard HL
SL, The cognitive-affective neuro-
et al, Cerebral glucose metabo-
science of obsessive-compulsive
lism in childhood-onset obses-
disorder, Current Psychiatric Rev
sive-compulsive disorder:
(2000) 2:341–6.
revisualization during pharma-
3 Cummings JL, Frontal-subcortical cotherapy, Arch Gen Psychiatry
circuits and human behavior. (1992) 49:690–4.
Arch Neurol (1993) 50:873–80.
8 Stein DJ, van Heerden B, Wes-
4 Robbins TW, Brown VJ, The role sels CJ et al, Single photon emis-
of the striatum in the mental sion tomography of the brain with
chronometry of action: a theoreti- Tc-99m HMPAO during sumatrip-
cal review, Rev Neurosci (1990) tan challenge in obsessive-
2:181–213. compulsive disorder: investigating
5 Saint-Cyr JA, Taylor AE, Nichol- the functional role of the serotonin
son K, Behavior and the basal auto-receptor, Prog Neuropsy-
ganglia. In: WJ Weiner, AE Lang chopharmacol Biol Psychiatry
(eds) Behavioral Neurology of (1999) 23:1079–99.
9 Hollander E, Prohovnik I, Stein (John Wiley: Chichester, 1995).

DJ, Obsessions and cerebral 18 Rapoport JL, The Boy Who
blood flow during pharmacologi- Couldn’t Stop Washing: The
cal challenge with m-CPP, J Neu- Experience and Treatment of
ropsychiatr Clin Neurosci (1995) Obsessive Compulsive Disorder
7:485–90. (Dutton: New York, 1989).
10 Zohar J, Mueller EA, Insel TR et 19 Stein DJ, Hollander E, Cognitive
al, Serotonergic responsivity in science and obsessive-
obsessive-compulsive disorder: compulsive disorder. In: Stein DJ,
comparison of patients and Young JE (eds) Cognitive Sci-
healthy controls, Arch Gen Psy- ence and Clinical Disorders (Aca-
chiatry (1987) 44:946–51. demic Press: San Diego, 1992).
11 Stein DJ, Hollander E, Impulsive 20 McDougle CJ, Goodman WK,
aggression and obsessive- Leckman JF et al, Haloperidol
compulsive disorder, Psychiatr addition in fluvoxamine-refractory
Ann (1993) 23:389–95. obsessive-compulsive disorder: a
12 Fineberg NA, Montgomery SA, double-blind placebo-controlled
Cowen PJ, Neuroendocrine study in patients with and without
responses to intravenous L-tryp- tics, Arch Gen Psychiatry (1994)
tophan in obsessive compulsive 51:302–8.
disorder, J Affect Disord (1994) 21 Baxter LR, Schwartz JM,
32:97–104. Bergman KS et al, Caudate glu-
13 Fineberg NA, Roberts A, Mont- cose metabolic rate changes with
gomery SA, Cowan PJ, Brain both drug and behavior therapy
5-HT function in obsessive com- for OCD, Arch Gen Psychiatry
pulsive disorder. Prolactin (1992) 49:681–9.
responses to d-fenfluramine, Br J 22 Martin LJ, Spicer DM, Lewis MH,
Psychiatry (1997) 171:280–2. Gluck JP, Cork LC, Social depri-
14 Hollander E, DeCaria C, Nitescu vation of infant monkeys alters the
A et al, Serotonergic function in chemoarchitecture of the brain:
obsessive compulsive disorder: I. Subcortical regions, J Neurosci
behavioral and neuroendocrine (1991) 11:3344–58.
responses to oral m-CPP and fen- 23 Swedo SE, Leonard HL, Garvey
fluramine in patients and healthy M et al, Pediatric autoimmune
volunteers, Arch Gen Psychiatry neuropsychiatric disorders asso-
(1992) 49:21–8. ciated with streptococcal infec-
15 Freud S, Inhibitions, symptoms tions: clinical description of the
and anxiety. (1926) Standard Edi- first 50 cases, Am J Psychiatry
tion of the Complete Psychologi- (1998) 155:264–71.
cal Works of Sigmund Freud, 24 Garvey MA, Perlmutter SA, Allen
vol. 20 (Hogarth Press: London) AJ et al, A pilot study of penicillin
111–31. prophylaxis for neuropsychiatric
16 Hollander E, Stein DJ, Broatch J, exacerbations triggered by strep-
Himelein C, Rowland C, A phar- tococcal infections, Biol Psychia-
macoeconomic and quality of life try (1999) 45:1564–71.
study of obsessive-compulsive 25 Fineberg N, Roberts A, Drummond
disorder, CNS Spectr (1997) 2: L, Should we combine drug and
16–25. exposure treatments in OCD?
17 Tallis F, Obsessive Compulsive World Psychiatric Association: The
Disorder: A Cognitive and Neu- Synthesis Between Psychophar-
ropsychological Perspective macology and Psychotherapy,
Jerusalem, Israel, 16–21 Novem- B. Behavioral psychotherapy for

ber 1997. children and adolescents with
26 Picinelli M, Pini S, Bellatuono C et obsessive compulsive disorder:
al, Efficacy of drug treatment in an open trial of a new protocol
obsessive compulsive disorder, A driven treatment package, J Am
meta-analytic review, Br J Psychi- Acad Child Adolesc Psych (1994)
atry (1995) 166:424–43. 33:333–41.
27 Marks IM, Stern RS, Mawson D et 32 Stein DJ, Rapoport JL, Cross-
al, Clomipramine and exposure cultural studies and obsessive-
for obsessive compulsive rituals. compulsive disorder, CNS Spectr
I, Br J Psychiatry (1980) 136: (1996) 1:42–6.
1–25. 33 Hollander E, Greenwald S, Neville
28 Marks IM, Lelliott P, Basoglu M et D et al, Uncomplicated and
al, Clomipramine, self exposure comorbid obsessive-compulsive
and therapist aided exposure for disorder in an epidemiological
obsessive compulsive rituals, Br J sample, Depress Anxiety
Psychiatry (1988) 152:522–34. (1996–7) 4:111–19.
29 Cottraux J, Mollard E, Bouvard M 34 Stein DJ, Psychiatry on the inter-
et al, A controlled study of fluvox- net: survey of an OCD mailing list,
amine and exposure in obsessive Psychiatr Bull (1996) 20:1–4.
compulsive disorder, Int Clin Psy- 35 Calvocoressi L, Lewis B, Harris M
chopharmacol (1990) 5:17–30. et al, Family accommodation in
30 Hohagen F, Winkelmann G, obsessive-compulsive disorder,
Rasche-Rauchle H et al, Combi- Am J Psychiatry (1995) 152:
nation of behaviour therapy with 441–3.
fluvoxamine in comparison with 36 Bystritsky A, Munford PR, Rosen
behaviour therapy and placebo: RM et al, A preliminary study of
results of a multicentre study, Br J partial hospital management of
Psychiatry (1998) 173(suppl. 35): severe obsessive-compulsive dis-
71–8. order, Psychiatr Serv (1996)
31 March JS, Mulle K, Herbel 47:170–4.
14
Patients’ perspectives on OCD
Frederick Toates
Abandoning modesty for a moment, I can claim to have a particular

expertise on the subject of obsessive compulsive disorder (OCD), being
both psychologist and sufferer. As a psychologist studying motivation,
emotion and the control of behaviour, a probably fruitful, though not
entirely welcome, cooperation is possible between two fundamental
aspects of myself.
In 1973, somewhat in the fashion of a Woody Allen movie, I was over-
come by intrusive, fearful and depressing obsessional thoughts about
death and thereby the futility of a finite life. Although the appearance of
these thoughts was sudden and dramatic, they came against a back-
ground of life-long chronic worry. On the one level, I could justify partly
the contents of the intrusive thoughts in terms of rationality; they did not
seem to be totally absurd. Indeed, the fact that Woody Allen can so
effectively tap urban everyman’s (and woman’s) existential fears is
indicative of this. However, what was clearly absurd and maladaptive
was the frequency and intensity with which the intrusions came into con-
scious awareness.
In the following 27 years, having tried virtually every treatment, conven-
tional and unconventional, I feel that I am in a good position to give some
insights. First, I will present some personal reflections and review the
insight that I gained from reactions to my autobiographical book. Then I
will briefly wear the hat of an experimental psychologist to try to relate
this to a scientific understanding.
Personal insight
Short of a miracle drug, a kind of chemical leucotomy, I accept that I

shall probably never be completely cured. However, I can cope with it. I
feel that there is a threshold, below which there exists a frequency and
intensity of intrusion that is tolerable. One can cope in the sense that life
has a net positive feel to it. When the frequency or intensity increases
177
beyond a certain level, life takes a quantum leap in a negative direction.

On first seeking help I felt somewhat foolish discussing the problem
with my doctor. It was not that he gave me any reason to feel odd, quite
the contrary. I just wished that there were some recognized neural abnor-
mality (‘hardware’) to which I could relate, rather than what appeared to
be a ‘software’ programming fault. My hunch is that the advent of selec-
tive serotonin reuptake inhibitors (SSRIs) has given a number of people
comfort in this direction.
Reactions to the book

After having published an autobiographical book about my experience
with the disorder,1 I was invited to appear on a number of television and
radio programmes, some being interactive with ‘phone-in’ listeners. I also
addressed self-help sufferers’ groups. I was overwhelmed by the expres-
sions of solidarity, concern and sympathy from fellow-sufferers. Some
people let me know that they were praying for me.
To a number of people the book was ‘open season’ to speculate wildly
about the causes of the problem – see, for example, the review by
Kwee.2 I even read that, unknown to me, I had been the victim of Satanic
ritual abuse – and that appeared in an article originating in a British uni-
versity! From colleagues came the message – ‘We would never have
known.’ I even heard the occasional ‘What is all the fuss about? Believe
me – there is nothing wrong with you, you work and function normally –
look at your work output.’ My strong feeling is that, in spite of the demise
of behaviourism as an explanatory tool in psychology, in reality people
tend to judge others almost entirely by their outward behaviour. If behav-
iour looks right then the assumption is that there can be little wrong.
I was surprised at the number of people – considered by me to be
‘healthily normal’ – who came up to me for a quiet chat along the follow-
ing lines: ‘I have never told anyone about this before, but some years ago
I found that I couldn’t stop checking the door. But it went away after a
month.’ Somewhat disconcerting for me was the very occasional person
(including one police officer) who reported the first appearance of (merci-
fully only transient) bouts of intrusive rumination triggered by reading
about a particular theme in my book!
One lady summed up the essence of many comments: ‘There is some-
thing particularly fascinating about being granted an insight into some-
one else’s inner, mental life.’ Virtually everyone congratulated me on the
quality of courage in going public, which perhaps says something about
the mind-set of people regarding acceptance of psychiatric disturbance.
I felt a sense of great responsibility and yet frustration in dealing with
the people who wrote to me. I wished that I could have suggested a
magic cure. Perhaps the clearest message to come from the sufferers
Patients’ perspectives 179
was a feeling of isolation and oddness. Some had, up to then, felt sure
that they alone had the condition. One man wrote:
I felt like an alien. It was very difficult to believe that there were other
people out there who were experiencing the same problems as I was
and the great depressing rarely-receding pain. Now I feel like part of a
club. Albeit a very odd club.
Some revealed just how well they had managed to camouflage their
OCD. Very many asked me, in pleading terms, if there was any light at
the end of the tunnel. Some were relieved to know that they were not psy-
chotic. From a self-help group in Hampshire, I received the comment:
Our group now refer to you as ‘Fred’ as I hope you don’t mind us call-
ing you and wish to congratulate you on your most interesting and
comforting dialogue. We, as a group, know that we are not alone and
are definitely not ‘mad’.
The biggest comfort from the book was that readers felt less odd that
someone had gone public. A number said that they felt they were mis-
understood souls struggling against prejudice, and they hoped that an
increase of information in the broader domain would help the general
public gain greater understanding of the condition and become more
accepting of it. It was highly significant to them that here was a personal
angle, not simply that of an expert. Some appeared alienated from the
world and were desperate for an intimate rapport. Others were comforted
by common features such as a shared star-sign, hobby or county of birth.
One lady even sent me a highlighted copy of my book, pointing out the
sections and words most relevant to her. One man, an engine driver,
drove down from Manchester and arrived at the university reception
office, burst into tears and refused to go until he had talked to me. On more
than one occasion I was told that the book had saved a life from suicide.
A number reported that, at last, they had found a recognized condition
from which they suffer. It has a name and they are legitimate sufferers. A
few people said that they felt more confident in describing the condition –
something along the lines of ‘I should have been able to tell all that to my
doctor, but lacked the confidence and framework.’ I seemed to form a
frame of reference for them: ‘Look – he is a successful academic and so I
can’t be so strange after all.’ They would tell me, ‘I found the book by
accident and then I realized that’s me exactly.’ Some went to their doc-
tors clutching my book as support for requesting an SSRI.
I also glimpsed the creative talent out there amongst sufferers and their
families in terms of such things as attempts to provide augmented feed-
back about things checked. One family had devised a series of sticky
labels to be attached each evening to doors and windows. These would
then be peeled off by the checker and attached to a numbered board to

be presented, on completion, to the partner. Similarly, the method of aug-
menting feedback in labelling checks that I employed on myself has
been investigated as a therapeutic tool and there are suggestions that it
is useful for some people.3,4
A number reported their despair at trying one thing after another with
no tangible results. A significant number reported great difficulty getting
the right professional help – feeling themselves to be treated as oddballs
and misunderstood. Several said that they had not talked to anyone
about their condition, believing that they were alone or that no help could
be obtained. Some people asked for reassurance, putting me almost in
the role of guru: ‘Well, you must be able to convince me that I am not
evil.’ A number sent their life histories in page after page of detailed
account. Perhaps not surprisingly, obsessionals are nothing if not good
diarists and documenters!
My clear impression was that, in many cases, OCD sprang from a con-
text of stress and conflict, for example existential crises on the meaning
of life, abuse, drug addiction and unemployment.
In terms of access to treatment, regional variations became evident
both in the UK and, based on a couple of letters, in France. Professionals
often did not know what to do. The proximity to a good centre with an
understanding therapist seemed out of reach to many.
Amongst therapists the book was generally well received. However,
one reviewer (Kwee) suggested that it might give a misleading impres-
sion that ‘quick fixes’ such as behaviour therapy and chemical cures are
viable.2 He suggested that the OC personality needs untangling. Another
reviewer said that she would be reluctant to recommend the book to her
patients on the grounds that it might increase their despair: if a psycholo-
gist can’t get cured, what hope is there for them?
So can such personal experience mesh with scientific insight?
Links with a scientific approach
A number of authors have suggested that behaviour is the product of

parallel processes of control.5,6 Crudely dichotomized, these can be
characterized by (a) relatively fast, ‘on-line’, direct, inflexible, stimulus-
response (S–R) links, and (b) slower, ‘off-line’, indirect, flexible, cognitive
processes.7,8 The resultant behaviour represents the resolution of these
two influences, which can cooperate or, at times, be in conflict. With
development, learning or brain damage, the relative weight of these fac-
tors can change. Thought itself also appears to be the product of a simi-
lar set of parallel processes.9,10 Could such a model be useful for
understanding OCD?
My own phenomenological experience would suggest that it can. At
Patients’ perspectives 181
times, thoughts appear to be triggered directly by particular appropriate

stimuli, such as seeing an assassination attempt on television. Con-
versely, sometimes they appear to be cued by a suggestion of resolution:
now things look good, that particular problem is solved. It feels as if there
is a queue for processing space, and resolution of a temporary problem
permits the obsessional thought to take over.
At other times, negative thoughts appear to pop into consciousness
without external trigger cues. Rather, they seem to be a result of work
going on at an unconscious level. It seems as if they are tagged at this
level ‘for further attention’ or ‘pending’ and cannot be assimilated into the
vast array of memories held in a relatively inaccessible form. Some theo-
ries of consciousness see a limited and expensive workspace as being
the arena into which material is brought which has failed to be resolved
at a lower level.11 This is how it feels to me.
There is a growing appreciation of the role of feedback from the body
in determining central mood and emotion.12–14 My own feeling is that such
general factors might bias cognition in a negative direction. Hence,
stress quite unrelated to the disorder might exacerbate it. Diet could
even do this if it induces gastrointestinal discomfort.
Conclusion
I hope that phenomonological observation of the sufferer on his or her

own conscious mind and behaviour can be assimilated into more con-
ventional approaches. It would seem an obvious way forward. In his fore-
word to my book, Hans Eysenck expressed the wish that other
psychologists would come forward with details of their troubles. One
such is Chadwick, who has written on the topic of paranoia.15
Acknowledgement
I am grateful to Dr Richard Stevens of the Open University for his comments.
References
1 Toates F, Obsessional Thoughts for compulsive checking: an
and Behaviour (Thorsons: exploratory investigation, Clin
Wellingborough, 1990). Reprinted Psychol Psychother (1993) 1:
as Obsessive-Compulsive Disor- 45–52.
der (Thorsons: London, 1992). 4 Watts FN, An information-pro-
2 Kwee M, Book review, Behav Res cessing approach to compulsive
Ther (1991) 29:371–3. checking. Clin Psychol Psy-
3 Tallis F, Doubt reduction using chother (1995) 2:69–77.
distinctive stimuli as a treatment 5 Hirsh R, The hippocampus and
contextual retrieval of information 11 Baars BJ, In the Theater of Con-

from memory: a theory, Behav sciousness, (Oxford University
Biol (1974) 12:421–44. Press: New York, 1997).
6 Le Doux J, The Emotional Brain 12 Damasio AR, Descartes’ Error
(Weidenfeld & Nicolson: London, (Papermac: London, 1996).
1998). 13 Rosenbaum JF, Heninger G,
7 Toates F, The interaction of cogni- Vagus nerve stimulation for treat-
tive and stimulus-response ment-resistant depression, Biol
processes in the control of behav- Psychiatry (2000) 47:273–5.
iour. Neurosci Biobehav Rev 14 Rush AJ, George MS, Sackeim
(1998) 22:59–83. HA et al, Vagus nerve stimulation
8 Toates F, Biological Psychology: (VNS) for treatment-resistant
An Integrative Approach (Pren- depressions: a multicenter study,
tice-Hall: Harlow, 2001). Biol Psychiatry (2000) 47:276–86.
9 Epstein S, Integration of the cog- 15 Chadwick P, The stepladder to
nitive and the psychodynamic the impossible: a first hand phe-
unconscious, Am Psychol (1994) nomenological account of a
49:709–24. schizoaffective psychotic crisis,
10 Sloman SA, The empirical case J Ment Health (1993) 2:239–50.
for two systems of reasoning,
Psychol Bull (1996) 119:3–22.
Appendix 1: Major rating scales
Yale–Brown Obsessive Compulsive Scale (YBOCS)*†
General instructions
This rating scale is designed to rate the severity and type of symptoms in
patients with obsessive-compulsive disorder (OCD). In general, the items
depend on the patient’s report; however, the final rating is based on the
clinical judgment of the interviewer. Rate the characteristics of each item
during the prior week up until and including the time of the interview.
Scores should reflect the average (mean) occurrence of each item for the
entire week.
This rating scale is intended for use as a semistructured interview. The
interviewer should assess the items in the listed order and use the ques-
tions provided. However, the interviewer is free to ask additional ques-
tions for purposes of clarification. If the patient volunteers information at
any time during the interview, that information will be considered. Ratings
should be based primarily on reports and observations gained during the
interview. If you judge that the information being provided is grossly inac-
curate, then the reliability of the patient is in doubt and should be noted
accordingly at the end of the interview (item 19).
Additional information supplied by others (e.g., spouse or parent) may
be included in a determination of the ratings only if it is judged that (1)
such information is essential to adequately assessing symptom severity
and (2) consistent week-to-week reporting can be ensured by having the
same informant(s) present for each rating session.
Before proceeding with the questions, define ‘obsessions’ and ‘com-
pulsions’ for the patient as follows:
Obsessions are unwelcome and distressing ideas, thoughts, images
or impulses that repeatedly enter your mind. They may seem to occur
against your will. They may be repugnant to you, you may recognize
them as senseless, and they may not fit your personality.
Compulsions, on the other hand, are behaviors or acts that you feel
driven to perform, although you may recognize them as senseless or
*Developed by Wayne K Goodman, MD. *Steven A Rasmussen, MD, Lawrence H Price,

MD, Carolyn Mazure, PhD, George R Heninger, MD, Dennis S Charney, MD, Department of
Psychiatry, Yale University School of Medicine, and *Department of Psychiatry, Brown Uni-
versity School of Medicine. Used by permission.
†First Edition 7/86; revised 9/89.
Copyright Wayne K Goodman, MD, 1989
183
excessive. At times, you may try to resist doing them but this may
prove difficult. You may experience anxiety that does not diminish until
the behavior is completed.
Let me give you some examples of obsessions and compulsions.
An example of an obsession is the recurrent thought or impulse to
do serious physical harm to your children even though you never
would.
An example of a compulsion is the need to repeatedly check appli-
ances, water faucets, and the lock on the front door before you can
leave the house. While most compulsions are observable behaviors,
some are unobservable mental acts, such as silent checking or having
to recite nonsense phrases to yourself each time you have a bad
thought.
Do you have any questions about what these words mean?
[If not, proceed.]
On repeated testing it is not always necessary to reread these defini-
tions and examples as long as it can be established that the patient
understands them. It may be sufficient to remind the patient that obses-
sions are the thoughts or concerns and compulsions are the things you
feel driven to do, including covert mental acts.
Have the patient enumerate current obsessions and compulsions in
order to generate a list of target symptoms. Use the YBOCS Symptom
Checklist as an aid for identifying current symptoms. It is also useful to
identify and be aware of past symptoms since they may reappear during
subsequent ratings. Once the current types of obsessions and compul-
sions are identified, organize and list them on the Target Symptoms form
according to clinically convenient distinctions (e.g., divide target compul-
sions into checking and washing). Describe salient features of the symp-
toms so that they can be more easily tracked (e.g., in addition to listing
checking, specify what the patient checks for). Be sure to indicate which
are the most prominent symptoms (i.e., those that will be the major focus
of assessment). Note, however, that the final score for each item should
reflect a composite rating of all of the patient’s obsessions or
compulsions.
The rater must ascertain whether reported behaviors are bona fide
symptoms of OCD and not symptoms of another disorder, such as simple
phobia or a paraphilia. The differential diagnosis between certain com-
plex motor tics and certain compulsions (e.g., involving touching) may be
difficult or impossible. In such cases, it is particularly important to provide
explicit descriptions of the target symptoms and to be consistent in sub-
sequent ratings. Separate assessment of tic severity with a tic rating
instrument may be necessary in such cases. Some of the items listed on
the YBOCS Symptom Checklist, such as trichotillomania, are currently
classified in DSM-III-R as symptoms of an impulse control disorder. It
Appendix 1 185
should be noted that the suitability of the YBOCS for use in disorders
other than DSM-III-R–defined OCD has yet to be established. However,
when using the YBOCS to rate severity of symptoms not strictly classified
under OCD (e.g., trichotillomania) in a patient who otherwise meets crite-
ria for OCD, it has been our practice to administer the YBOCS twice;
once for conventional obsessive-compulsive symptoms and a second
time for putative OCD-related phenomena. In this fashion separate
YBOCS scores are generated for severity of OCD and severity of other
symptoms in which the relationship to OCD is still unsettled.
On repeated testing, review and, if necessary, revise target obsessions
prior to rating item 1. Do likewise for compulsions prior to rating item 6.
All 19 items are rated, but only items 1–10 (excluding items 1b and 6b)
are used to determine the total score. The total YBOCS score is the sum
of items 1–10 (excluding 1b and 6b), whereas the obsession and com-
pulsion subtotals are the sums of items 1–5 (excluding 1b) and 6–10
(excluding 6b), respectively.
Because at the time of this writing (9/89) there are limited data regard-
ing the psychometric properties of items 1b, 6b, and 11–16, these items
should be considered investigational. Until adequate studies of the relia-
bility, validity, and sensitivity to change of these items are conducted, we
must caution against placing much weight on results derived from these
item scores. These important caveats aside, we believe that items 1b
(obsession-free interval), 6b (compulsion-free interval), and 12 (avoid-
ance) may provide information that has bearing on the severity of
obsessive-compulsive symptoms. Item 11 (insight) may also furnish use-
ful clinical information. We are least secure about the usefulness of items
13–16.
Items 17 (global severity) and 18 (global improvement) have been
adapted from the Clinical Global Impression Scale to provide measures
of overall functional impairment associated with, but not restricted to, the
presence of obsessive-compulsive symptoms. Disability produced by
secondary depressive symptoms would also be considered when rating
these items. Item 19, which estimates the reliability of the information
reported by the patient, may assist in the interpretation of scores on other
YBOCS items in some cases of OCD.
See over for checklist.
YBOCS symptom checklist (9/89)

Name _____________________________________ Date _____________________
________________________________________________________________________
Check all that apply, but clearly mark the principal symptoms with a ‘P.’
(Rater must ascertain whether reported behaviors are bona fide symptoms of
OCD, and not symptoms of another disorder such as simple phobia or
hypochondrias. Items marked ‘*’ may or may not be OCD phenomena.)
Current Past Aggressive Obsessions

____ ____ Fear might harm self
____ ____ Fear might harm others
____ ____ Violent or horrific images
____ ____ Fear of blurting out obscenities or insults
____ ____ Fear of doing something else embarrassing*
____ ____ Fear will act on unwanted impulses (e.g., to stab friend)
____ ____ Fear will steal things
____ ____ Fear will harm others because not careful enough (e.g., hit/run
MVA*)
____ ____ Fear will be responsible for something else terrible happening
(e.g., fire, burglary)
____ ____ Other ___________________________________________________
Contamination Obsessions
____ ____ Concerns or disgust with bodily waste or secretions (e.g., urine,
feces, saliva)
____ ____ Concern with dirt or germs
____ ____ Excessive concern with environment contaminants (e.g.,
asbestos, radiation, toxic waste)
____ ____ Excessive concern with household items (e.g., cleaners,
solvents)
____ ____ Excessive concern with animals (e.g., insects)
____ ____ Bothered by sticky substances or residues
____ ____ Concerned will get ill because of contaminant
____ ____ Concerned will get others ill by spreading contaminant
(aggressive)
____ ____ No concern with consequences of contamination other than
how it might feel
____ ____ Other ___________________________________________________
Sexual Obsessions
____ ____ Forbidden or perverse sexual thoughts, images, or impulses
____ ____ Content involves children or incest
____ ____ Content involves homosexuality*
____ ____ Sexual behavior toward others (aggressive)*
____ ____ Other ___________________________________________________
Hoarding/Saving Obsessions
[distinguish from hobbies and concern with objects of monetary
or sentimental value]
____ ____ ________________________________________________________
*MVA ⫽motor vehicle accident

Appendix 1 187
Religious Obsessions (scrupulosity)

____ ____ Concerned with sacrilege and blasphemy
____ ____ Excess concern with right/wrong, morality
____ ____ Other ___________________________________________________
Obsession with Need for Symmetry or Exactness

____ ____ Accompanied by magical thinking (e.g., concerned that mother
will have accident unless things are in the right place)
____ ____ Not accompanied by magical thinking
Miscellaneous Obsessions
____ ____ Need to know or remember
____ ____ Fear of saying certain things
____ ____ Fear of not saying just the right thing
____ ____ Fear of losing things
____ ____ Intrusive (nonviolent) images
____ ____ Intrusive nonsense sounds, words, or music
____ ____ Bothered by certain sounds/noises*
____ ____ Lucky/unlucky numbers
____ ____ Colors with special significance
____ ____ Superstitious fears
____ ____ Others __________________________________________________
Somatic Obsessions
____ ____ Concern with illness or disease*
____ ____ Excessive concern with body part or aspect of appearance
(e.g., dysmorphophobia)*
____ ____ Other ___________________________________________________
Cleaning/Washing Compulsions
____ ____ Excessive or ritualized handwashing
____ ____ Excessive or ritualized showering, bathing, toothbrushing,
grooming, or toilet routine
____ ____ Involves cleaning of household items or other inanimate objects
____ ____ Other measures to prevent or remove contact with
contaminants
____ ____ Other ___________________________________________________
Checking Compulsions
____ ____ Checking locks, stove, appliances, etc.
____ ____ Checking that did not/will not harm others
____ ____ Checking that did not/will not harm self
____ ____ Checking that nothing terrible did/will happen
____ ____ Checking that did not make mistake
____ ____ Checking tied to somatic obsessions
____ ____ Other ___________________________________________________
Repeating Rituals
____ ____ Rereading or rewriting
____ ____ Need to repeat routine activities (e.g., in/out door, up/down
from chair)
____ ____ Other ___________________________________________________
Counting Compulsions
____ ____ ________________________________________________________
Ordering/Arranging Compulsions
____ ____ ________________________________________________________
Hoarding/Collecting Compulsions
[distinguish from hobbies and concern with objects of monetary
or sentimental value (e.g., carefully reads junk mail, piles up old
newspapers, sorts through garbage, collects useless objects)]
____ ____ ________________________________________________________
Miscellaneous Compulsions
____ ____ Mental rituals (other than checking/counting)
____ ____ Excessive listmaking
____ ____ Need to tell, ask, or confess
____ ____ Need to touch, tap, or rub*
____ ____ Rituals involving blinking or staring*
____ ____ Measures (not checking) to prevent
harm to self ____, harm to others ____, terrible
consequences ____
____ ____ Ritualized eating behaviors*
____ ____ Superstitious behaviors
____ ____ Trichotillomania*
____ ____ Other self-damaging or self-mutilating behaviors*
____ ____ Other ___________________________________________________
Target symptom list

Name ________________________________ Date ____________________________
Obsessions
1. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
2. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
3. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Compulsions
1. _____________________________________________________________________
______________________________________________________________________
Appendix 1 189
______________________________________________________________________
______________________________________________________________________
2. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
3. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Avoidance
1. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
2. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
3. _____________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Yale-Brown Obsessive Compulsive Scale (YBOCS)

‘I am now going to ask several questions about your obsessive thoughts.’
[Make specific reference to the patient’s target obsessions.]
1. Time Occupied by Obsessive Thoughts

• How much of your time is occupied by obsessive thoughts? [When
obsessions occur as brief, intermittent intrusions, it may be difficult to
assess time occupied by them in terms of total hours. In such cases,
estimate time by determining how frequently they occur. Consider both
the number of times the intrusions occur and how many hours of the
day are affected. Ask: How frequently do the obsessive thoughts
occur? [Be sure to exclude ruminations and preoccupations, which,
unlike obsessions, are ego-syntonic and rational (but exaggerated).]
0—None.
1—Mild, less than 1 hr/day or occasional intrusion
2—Moderate, 1 to 3 hr/day or frequent intrusion
3—Severe, greater than 3 and up to 8 hr/day or very frequent intrusion

4—Extreme, greater than 8 hr/day or near constant intrusion
1b. Obsession-Free Interval (not included in total score)

• On the average, what is the longest number of consecutive waking
hours per day that you are completely free of obsessive thoughts? [If
necessary, ask: What is the longest block of time in which obsessive
thoughts are absent?]
0—No symptoms
1—Long symptom-free interval, more than 8 consecutive hrs/day
symptom free
2—Moderately long symptom-free interval, more than 3 and up to 8
consecutive hrs/day symptom free
3—Short symptom-free interval, from 1 to 3 consecutive hrs/day symp-
tom free
4—Extremely short symptom-free interval, less than 1 consecutive
hr/day symptom free
2. Interference Due to Obsessive Thoughts

• How much do your obsessive thoughts interfere with your social or
work (or role) functioning? Is there anything that you don’t do because
of them? [If currently not working determine how much performance
would be affected if patient were employed.]
0—None
1—Mild, slight interference with social or occupational activities, but
overall performance not impaired
2—Moderate, definite interference with social or occupational perfor-
mance, but still manageable
3—Severe, causes substantial impairment in social or occupational
performance
4—Extreme, incapacitating
3. Distress Associated with Obsessive Thoughts

• How much distress do your obsessive thoughts cause you?
[In most cases, distress is equated with anxiety; however, patients may
report that their obsessions are ‘disturbing’ but deny ‘anxiety.’ Only rate
anxiety that seems triggered by obsessions, not generalized anxiety or
anxiety associated with other conditions.]
0—None
1—Mild, not too disturbing
2—Moderate, disturbing, but still manageable
3—Severe, very disturbing
4—Extreme, near constant and disabling distress
Appendix 1 191
4. Resistance Against Obsessions

• How much of an effort do you make to resist the obsessive thoughts?
How often do you try to disregard or turn your attention away from
these thoughts as they enter your mind? [Only rate effort made to
resist, not success or failure in actually controlling the obsessions. How
much the patient resists the obsessions may or may not correlate with
his/her ability to control them. Note that this item does not directly mea-
sure the severity of the intrusive thoughts; rather it rates a manifestation
of health, i.e., the effort the patient makes to counteract the obsessions
by means other than avoidance or the performance of compulsions.
Thus, the more the patient tries to resist, the less impaired is this
aspect of his/her functioning. There are ‘active’ and ‘passive’ forms of
resistance. Patients in behavioral therapy may be encouraged to coun-
teract their obsessive symptoms by not struggling against them (e.g.,
‘just let the thoughts come’) passive opposition, or by intentionally
bringing on the disturbing thoughts. For the purposes of this item, con-
sider use of these behavioral techniques as forms of resistance. If the
obsessions are minimal, the patient may not feel the need to resist
them. In such cases, a rating of ‘0’ should be given.]
0—Makes an effort to always resist, or symptoms so minimal doesn’t
need to actively resist
1—Tries to resist most of the time
2—Makes some effort to resist
3—Yields to all obsessions without attempting to control them, but
does so with some reluctance
4—Completely and willingly yields to all obsessions
5. Degree of Control over Obsessive Thoughts

• How much control do you have over your obsessive thoughts? How
successful are you in stopping or diverting your obsessive thinking?
Can you dismiss them? [In contrast to the preceding item on resis-
tance, the ability of the patient to control his obsessions is more closely
related to the severity of the intrusive thoughts.]
0—Complete control
1—Much control, usually able to stop or divert obsessions with some
effort and concentration
2—Moderate control, sometimes able to stop or divert obsessions
3—Little control, rarely successful in stopping or dismissing obses-
sions, can only divert
4—No control, experienced as completely involuntary, rarely able to
even momentarily alter obsessive thinking
‘The next several questions are about your compulsive behaviors.’ [Make
specific reference to the patient’s target compulsions.]
6. Time Spent Performing Compulsive Behaviors

• How much time do you spend performing compulsive behaviors?
[When rituals involving activities of daily living are chiefly present, ask:
How much longer than most people does it take to complete routine
activities because of your rituals? When compulsions occur as brief,
intermittent behaviors, it may be difficult to assess time spent perform-
ing them in terms of total hours. In such cases, estimate time by deter-
mining how frequently they are performed. Consider both the number
of times compulsions are performed and how many hours of the day
are affected. Count separate occurrences of compulsive behaviors, not
number of repetitions; e.g., a patient who goes into the bathroom 20
different times a day to wash his hands 5 times very quickly, performs
compulsions 20 times a day, not 5 or 5 ⫻ 20 ⫽ 100. Ask: How fre-
quently do you perform compulsions? In most cases compulsions are
observable behaviors (e.g., hand washing), but some compulsions are
covert (e.g., silent checking).]
0—None
1—Mild (spends less than 1 hr/day performing compulsions) or occa-
sional performance of compulsive behaviors
2—Moderate (spends from 1 to 3 hrs/day performing compulsions) or
frequent performance of compulsive behaviors
3—Severe (spends more than 3 and up to 8 hrs/day performing com-
pulsions) or very frequent performance of compulsive behaviors
4—Extreme (spends more than 8 hrs/day performing compulsions) or
near constant performance of compulsive behaviors (too numerous
to count)
6b. Compulsion-Free Interval (not included in total sore)

• On the average, what is the longest number of consecutive waking
hours per day that you are completely free of compulsive behavior? [If
necessary, ask: What is the longest block of time in which compulsions
are absent?]
0—No symptoms
1—Long symptom-free interval, more than 8 consecutive hrs/day
symptom free
2—Moderately long symptom-free interval, more than 3 and up to 8
consecutive hrs/day symptom free
3—Short symptom-free interval, from 1 to 3 consecutive hrs/day symp-
tom free.
4—Extremely short symptom-free interval, less than 1 consecutive
hr/day symptom free
Appendix 1 193
7. Interference due to Compulsive Behaviors

• How much do your compulsive behaviors interfere with your social or
work (or role) functioning? Is there anything that you don’t do because
of the compulsions? [If currently not working determine how much per-
formance would be affected if patient were employed.]
0—None
1—Mild, slight interference with social or occupational activities, but
overall performance not impaired
2—Moderate, definite interference with social or occupational perfor-
mance, but still manageable
3—Severe, causes substantial impairment in social or occupational
performance
8. Distress Associated with Compulsive Behavior

• How would you feel if prevented from performing your compulsions(s)?
[Pause] How anxious would you become? [Rate degree of distress
patient would experience if performance of the compulsion were sud-
denly interrupted without reassurance offered. In most, but not all
cases, performing compulsions reduces anxiety. If, in the judgment of
the interviewer, anxiety is actually reduced by preventing compulsions
in the manner described above, then ask: How anxious do you get
while performing compulsions until you are satisfied they are
completed?]
0—None
1—Mild only slightly anxious if compulsions prevented, or only slight
anxiety during performance of compulsions
2—Moderate, reports that anxiety would mount but remain manage-
able if compulsions prevented, or that anxiety increases but
remains manageable during performance of compulsions
3—Severe, prominent and very disturbing increase in anxiety if com-
pulsions interrupted, or prominent and very disturbing increase in
anxiety during performance of compulsions
4—Extreme, incapacitating anxiety from any intervention aimed at
modifying activity, or incapacitating anxiety develops during perfor-
mance of compulsions
9. Resistance Against Compulsions

• How much of an effort do you make to resist the compulsions? [Only
rate effort made to resist, not success or failure in actually controlling
the compulsions. How much the patient resists the compulsions may or
may not correlate with his ability to control them. Note that this item
does not directly measure the severity of the compulsions; rather it

rates a manifestation of health, i.e., the effort the patient makes to
counteract the compulsions. Thus, the more the patient tries to resist,
the less impaired is this aspect of his functioning. If the compulsions
are minimal, the patient may not feel the need to resist them. In such
cases, a rating of ‘0’ should be given.]
0—Makes an effort to always resist, or symptoms so minimal doesn’t
need to actively resist
1—Tries to resist most of the time
2—Makes some effort to resist
3—Yields to almost all compulsions without attempting to control them,
but does so with some reluctance
4—Completely and willingly yields to all compulsions
10. Degree of Control over Compulsive Behavior

• How strong is the drive to perform the compulsive behavior? [Pause]
How much control do you have over the compulsions? [In contrast to
the preceding item on resistance, the ability of the patient to control his
compulsions is more closely related to the severity of the compulsions.]
1—Much control, experiences pressure to perform the behavior but
usually able to exercise voluntary control over it
2—Moderate control, strong pressure to perform behavior, can control
it only with difficulty
3—Little control, very strong drive to perform behavior, must be carried
to completion, can only delay with difficulty
4—No control, drive to perform behavior experienced as completely
involuntary and overpowering, rarely able to even momentarily
delay activity
‘The remaining questions are about both obsessions and compulsions.

Some ask about related problems.’ These are investigational items not
included in total YBOCS score but may be useful in assessing these
symptoms.
11. Insight into Obsessions and Compulsions

• Do you think your concerns or behaviors are reasonable? [Pause] What
do you think would happen if you did not perform the compulsion(s)?
Are you convinced something would really happen? [Rate patient’s
insight into the senselessness or excessiveness of his obsession(s)
based on beliefs expressed at the time of the interview.]
0—Excellent insight, fully rational
1—Good insight. Readily acknowledges absurdity or excessiveness of
thoughts or behaviors but does not seem completely convinced
Appendix 1 195
that there isn’t something besides anxiety to be concerned about

(i.e., has lingering doubts)
2—Fair insight. Reluctantly admits thoughts or behavior seem unrea-
sonable or excessive, but wavers. May have some unrealistic fears,
but no fixed convictions
3—Poor insight. Maintains that thoughts or behaviors are not unreason-
able or excessive, but acknowledges validity of contrary evidence
(i.e., overvalued ideas present)
4—Lacks insight, delusional. Definitely convinced that concerns and
behavior are reasonable, unresponsive to contrary evidence
12. Avoidance
• Have you been avoiding doing anything, going any place, or being
with anyone because of your obsessional thoughts or out of concern
you will perform compulsions? [If yes, then ask: How much do you
avoid? Rate degree to which patient deliberately tries to avoid things.
Sometimes compulsions are designed to ‘avoid’ contact with some-
thing that the patient fears. For example, clothes washing rituals would
be designated as compulsions, not as avoidant behavior. If the patient
stopped doing the laundry then this would constitute avoidance.]
0—No deliberate avoidance
1—Mild, minimal avoidance
2—Moderate, some avoidance; clearly present
3—Severe, much avoidance; avoidance prominent
4—Extreme, very extensive avoidance; patient does almost everything
he/she can to avoid triggering symptoms
13. Degree of Indecisiveness

• Do you have trouble making decisions about little things that other peo-
ple might not think twice about (e.g., which clothes to put on in the
morning; which brand of cereal to buy)? [Exclude difficulty making
decisions which reflect ruminative thinking. Ambivalence concerning
rationally-based difficult choices should also be excluded.]
0—None
1—Mild, some trouble making decisions about minor things
2—Moderate, freely reports significant trouble making decisions that
others would not think twice about
3—Severe, continual weighing of pros and cons about nonessentials
4—Extreme, unable to make any decisions. Disabling
14. Overvalued Sense of Responsibility

• Do you feel very responsible for the consequences of your actions? Do
you blame yourself for the outcome of events not completely in your
control? [Distinguish from normal feelings of responsibility, feelings of
worthlessness, and pathological guilt. A guilt-ridden person experi-
ences himself or his actions as bad or evil.]
0—None
1—Mild, only mentioned on questioning, slight sense of over-
responsibility
2—Moderate, ideas stated spontaneously, clearly present; patient
experiences significant sense of over-responsibility for events out-
side his/her reasonable control
3—Severe, ideas prominent and pervasive; deeply concerned he/she
is responsible for events clearly outside his control. Self-blaming
farfetched and nearly irrational
4—Extreme, delusional sense of responsibility (e.g., if an earthquake
occurs 3,000 miles away patient blames herself because she didn’t
perform her compulsions)
15. Pervasive Slowness/Disturbance of Inertia

• Do you have difficulty starting or finishing tasks? Do many routine activ-
ities take longer than they should? [Distinguish from psychomotor retar-
dation secondary to depression. Rate increased time spent performing
routine activities even when specific obsessions cannot be identified.]
0—None
1—Mild, occasional delay in starting or finishing
2—Moderate, frequent prolongation of routine activities but tasks usu-
ally completed. Frequently late
3—Severe, pervasive and marked difficulty initiating and completing
routine tasks. Usually late
4—Extreme, unable to start or complete routine tasks without full
assistance
16. Pathological Doubting

• After you complete an activity do you doubt whether you performed it
correctly? Do you doubt whether you did it at all? When carrying out
routine activities do you find that you don’t trust your senses (i.e., what
you see, hear, or touch)?
0—None
1—Mild, only mentioned on questioning, slight pathological doubt.
Examples given may be within normal range
2—Moderate, ideas stated spontaneously, clearly present and appar-
ent in some of patient’s behaviors; patient bothered by significant
pathological doubt. Some effect on performance but still manage-
able
Appendix 1 197
3—Severe, uncertainty about perceptions or memory prominent;

pathological doubt frequently affects performance
4—Extreme, uncertainty about perceptions constantly present; patho-
logical doubt substantially affects almost all activities. Incapacitat-
ing (e.g., patient states ‘my mind doesn’t trust what my eyes see’)
[Items 17 and 18 refer to global illness severity. The rater is required to
consider global function, not just the severity of obsessive-compulsive
symptoms.]
17. Global Severity

Interviewer’s judgment of the overall severity of the patient’s illness.
Rated from 0 (no illness) to 6 (most severe patient seen). [Consider the
degree of distress reported by the patient, the symptoms observed,
and the functional impairment reported. Your judgment is required both
in averaging this data as well as weighing the reliability or accuracy of
the data obtained. This judgment is based on information obtained dur-
ing the interview.]
0—No illness
1—Illness slight, doubtful, transient; no functional impairment
2—Mild symptoms, little functional impairment
3—Moderate symptoms, functions with effort
4—Moderate – severe symptoms, limited functioning
5—Severe symptoms, functions mainly with assistance
6—Extremely severe symptoms, completely nonfunctional
18. Global Improvement

Rate total overall improvement present since the initial rating, whether
or not, in your judgment, it is due to drug treatment.
0—Very much worse
1—Much worse
2—Minimally worse
3—No change
4—Minimally improved
5—Much improved
6—Very much improved
19. Reliability
Rate the overall reliability of the rating scores obtained. Factors that
may affect reliability include the patient’s cooperativeness and his/her
natural ability to communicate. The type and severity of obsessive-
compulsive symptoms present may interfere with the patient’s concen-
tration, attention, or freedom to speak spontaneously (e.g., the content
of some obsessions may cause the patient to choose his words very
carefully).
0—Excellent, no reason to suspect data unreliable
1—Good, factor(s) present that may adversely affect reliability
2—Fair, factor(s) present that definitely reduce reliability
3—Poor, very low reliability
Items 17 and 18 are adapted from the Clinical Global Impression Scale
(Guy W: ECDEU Assessment Manual for Psychopharmacology: Publica-
tion 76-338. Washington, DC, US Department of Health, Education, and
Welfare, 1976).
Additional information regarding the development, use, and psycho-
metric properties of the YBOCS can be found in Goodman WK, Price LH,
Rasmussen SA, et al: The Yale–Brown Obsessive Compulsive Scale
(YBOCS). Part I: Development, use, and reliability. Arch Gen Psychiatry
(1989) 46:1006–11, and Goodman WK, Price LH, Rasmussen SA, et al:
The Yale–Brown Obsessive Compulsive Scale (YBOCS). Part II: Validity.
Arch Gen Psychiatry (1989) 46:1012–16.
Appendix 1 199
Yale–Brown Obsessive Compulsive Scale (9/89)

YBOCS total (add items 1–10) 䊐
Patient name __________________ Date ______________________
Patient ID _____________________ Rater _____________________
None Mild Moderate Severe Extreme

1. Time spent on obsessions 0 1 2 3 4
1b. Obsession-free interval No Moderately Extremely

Symptoms Long Long Short Short
(do not add to subtotal or total score) 0 1 2 3 4
2. Interference from obsessions 0 1 2 3 4

3. Distress of obsessions 0 1 2 3 4
Always Completely
Resists Yields
4. Resistance 0 1 2 3 4
Complete Much Moderate Little No
Control Control Control Control Control
5. Control over obsessions 0 1 2 3 4
Obsession subtotal (add items 1–5) 䊐

6. Time spent on compulsions 0 1 2 3 4
6b. Compulsion-free interval No Moderately Extremely

7. Interference from compulsions 0 1 2 3 4

8. Distress from compulsions 0 1 2 3 4
Always Completely
Resists Yields
10. Control over compulsions 0 1 2 3 4
Compulsion subtotal (add items 6–10) 䊐
Excellent Absent
11. Insight into O-C symptoms 0 1 2 3 4

12. Avoidance 0 1 2 3 4
13. Indecisiveness 0 1 2 3 4
14. Pathologic responsibility 0 1 2 3 4
15. Slowness 0 1 2 3 4
16. Pathologic doubting 0 1 2 3 4
17. Global severity 0 1 2 3 4 5 6

18. Global improvement 0 1 2 3 4 5 6
19. Reliability: Excellent ⫽ 0 Good ⫽ 1 Fair ⫽ 2 Poor ⫽ 3

Childrens’ Yale–Brown Obsessive Compulsive Scale

(CY–BOCS)
Developed by Wayne K Goodman, MD, Steven A Rasmussen, MD, Mark

A Riddle, MD, Lawrence H Price, MD, Judith L Rapoport, MD, of the
Department of Psychiatry, University of Florida College of Medicine;
Department of Psychiatry, Johns Hopkins University School of Medicine;
Department of Psychiatry, Brown University School of Medicine; Depart-
ment of Psychiatry, Yale University School of Medicine; and Child Psychi-
atric Branch, National Institute of Mental Health.
Investigators interested in using this rating scale should contact Dr
Goodman at the University of Florida, Department of Psychiatry, PO Box
100256, Gainesville, FL 32610.
Copyright Wayne K Goodman, MD, 1989. Reproduced with permission.
General instructions
Overview
This scale is designed to rate the severity of obsessive and compulsive
symptoms in children, ages 6 to 17 years. In general, the ratings depend
on the child’s and parent’s report, however, the final rating is based on
the clinical judgment of the interviewer. Rate the characteristics of each
item during the prior week up until and including the time of the interview.
Scores should reflect the average (mean) occurrence of each item for the
entire week, unless specified otherwise.
Informants
Ideally, information should be obtained by interviewing: (1) the parent(s)
or guardian alone, (2) the child alone and, (3) the child and parent(s)
together (to clarify differences). The preferred order for the interviews
may vary depending on the age and developmental level of the child or
adolescent. Information from each of these interviews should then be
combined to inform the scoring of each item. Consistent reporting can be
ensured by having the same informant(s) present for each rating session.
Definitions
Before proceeding with the questions, define ‘obsessions’ and ‘compul-
sions’ for the child and primary caretaker as follows:
‘Obsessions are thoughts, ideas, or pictures that keep coming into your
mind even though you do not want them to. They may be unpleasant, silly
or embarrassing.’
Appendix 1 201
‘An example of an obsession is the repeated thought that germs or dirt

are harming you or other people, or that something unpleasant may hap-
pen to your or someone special to you.’ These are thoughts that keep
coming back, over and over again.
‘Compulsions are things that you feel you have to do although you may
know that they do not make sense. Sometimes, you may try to stop from
doing them but this might not be possible. You might feel worried or
angry or frustrated until you have finished what you have to do.’
‘An example of a compulsion is the need to wash your hands over and
over again even though they are not really dirty, or the need to count up
to a certain number while you do certain things.’
‘Do you have any questions about what these words called compulsions
and obsessions mean?’
Symptom specificity
The rater must determine that reported behaviors are true obsessions or
compulsions and not other symptoms, such as phobias or anxious wor-
ries. The differential diagnosis between certain complex motor tics and
certain compulsions (e.g. touching or tapping) may be difficult or impos-
sible. In such cases, it is particularly important to provide explicit
descriptions of the target symptoms and to be consistent in including or
excluding these symptoms in subsequent ratings. Separate assessment
of tic severity with a tic rating instrument may be necessary in such
cases.
Some of the items listed on the CY–BOCS Symptom Checklist, such as
trichotillomania, are currently classified in DSM-III-R as symptoms of an
Impulse Control Disorder.
Items marked ‘*’ in the Symptom Checklist may or may not be obses-
sions or compulsions.
Procedure
This scale is designed to be used by a clinician in a semi-structured
interview format. After reviewing with the child and parent(s) the defini-
tions of obsessions and compulsions, inquire about specific compulsions
and complete the CY–BOCS Compulsions Checklist on pages 24–5.
Then complete the Target Symptom List for Compulsions on page 26.
Next, inquire about and note questions 6 through 10 on pages 26
through 29, repeat the above procedure for obsessions: review defini-
tions, complete the Obsessions Checklist on pages 20–2, complete the
Target Symptom List for obsessions on page 21–2, and inquire about
and rate questions 1 through 5 on pages 22–4.
Finally, inquire about and rate questions 11 through 19 on pages 29
through 32. Scoring can be recorded on the scoring sheet on page 33.
All ratings should be in whole integers.
Scoring
All 19 items are rated, but only items 1–10 are used to determine the total
score. The total CY–BOCS score is the sum of items 1–10, whereas the
obsession and compulsion subtotals are the sums of items 1–5 and 6–10,
respectively. 1B and 6B are not being used in the scoring.
Items 17 (global severity) and 18 (global improvement) are adapted
from the Clinical Global Impression Scale (Guy W, 1976: ECDEU Assess-
ment Manual for Psychopharmacology: Publication 76–338. Washington,
DC, US Department of Health, Education, and Welfare, 1976.) to provide
measures of overall functional impairment associated with the presence
of obsessive-compulsive symptoms.
Name ________________________________ Date ____________________________
CY-BOCS obsessions checklist

Check all that apply, but clearly mark the principal symptoms with a ‘P’. (Item
marked ‘*’ may or may not be OCD phenomena.)
Current Past Contamination Obsessions

____ ____ Concern with dirt, germs, certain illnesses (e.g., AIDS)
____ ____ Concern or disgust with bodily waste or secretions (e.g., urine,
feces, saliva)
____ ____ Excessive concern with environmental contaminants (e.g.,
asbestos, radiation, toxic waste)
____ ____ Excessive concern with household items (e.g., cleaners,
solvents)
____ ____ Excessive concern about animals/insects
____ ____ Excessively bothered by sticky substances or residues
____ ____ Concerned will get ill because of contaminant
____ ____ Concerned will get others ill by spreading contaminant
(aggressive)
____ ____ No concern with consequences of contamination other than
how it might feel*
____ ____ Other (describe) _________________________________________
Aggressive Obsessions
____ ____ Fear might harm self
____ ____ Fear might harm others
____ ____ Fear harm will come to self
____ ____ Fear harm will come to others because something child did or
did not do
____ ____ Violent or horrific images
____ ____ Fear of blurting out obscenities or insults
____ ____ Fear of doing something else embarrassing*
Appendix 1 203
____ ____ Fear will act on unwanted impulses (e.g., to stab a family
member)
____ ____ Fear will steal things
____ ____ Fear will be responsible for something else terrible happening
(e.g., fire, burglary, flood)
____ ____ Other (describe) _________________________________________
Sexual Obsessions
(Are you having any sexual thoughts? If yes, are they routine or
are they repetitive thoughts that you would rather not have or
find disturbing? If yes, are they:)
____ ____ Forbidden or perverse sexual thoughts, images, impulses
____ ____ Content involves homosexuality*
____ ____ Sexual behavior toward others (aggressive)*
____ ____ Other (describe) _________________________________________
Hoarding/Saving Obsessions
____ ____ Fear of losing things
Magical Thoughts/ Superstitious Obsessions

____ ____ Lucky/unlucky numbers
____ ____ Other (describe) _________________________________________
Somatic Obsessions
____ ____ Excessive concern with illness or disease*
____ ____ Excessive concern with body part or aspect of appearance
(e.g., dysmorphophobia)*
Religious Obsessions
____ ____ Excessive concern or fear of offending religious objects (God)
____ ____ Excess concern with right/wrong, morality
____ ____ Other (describe) _________________________________________
Miscellaneous Obsessions
____ ____ Need to know or remember
____ ____ Fear of saying certain things
____ ____ Fear of not saying just the right thing
____ ____ Intrusive (non-violent) images
____ ____ Intrusive sounds, words, music, or numbers
____ ____ Other (describe) _________________________________________
Target symptom list for obsessions

Obsessions (Describe, listing by order of severity):
1. _____________________________________________________________________
______________________________________________________________________
2. _____________________________________________________________________
______________________________________________________________________
3. _____________________________________________________________________
______________________________________________________________________
4. _____________________________________________________________________
______________________________________________________________________
Avoidance (Describe any avoidance behavior associated with obsessions; e.g.,
child avoids putting clothes away to prevent thoughts.)
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Questions on obsessions (items 1–5)
‘I am now going to ask you questions about the thoughts you cannot stop
thinking about.’
1. Time Occupied by Obsessive Thoughts

• How much time do you spend thinking about these things?
(When obsessions occur as brief, intermittent intrusions, it may be
impossible to assess time occupied by them in terms of total hours. In
such cases, estimate time by determining how frequently they occur.
Consider both the number of times the intrusions occur and how many
hours of the day are affected.)
• How frequently do these thoughts occur?

(Be sure to exclude ruminations and preoccupations which, unlike
obsessions, are ego-syntonic and rational [but exaggerated].)
0—None
1—Mild, less than 1 hr/day or occasional intrusion
2—Moderate, 1 to 3 hrs/day or frequent intrusion
3—Severe, greater than 3 and up to 8 hrs/day or very frequent
intrusion
4—Extreme, greater than 8 hrs/day or near constant intrusion
1b. Obsession-Free Interval (not included in total score)

• On the average, what is the longest amount of time each day that you
are not bothered by the obsessive thoughts?
0—None
1—Mild, long symptom free intervals or more than 8 consecutive
hrs/day symptom-free
2—Moderate, moderately long symptom-free intervals or more than 3
and up to 8 consecutive hrs/day symptom-free
Appendix 1 205
3—Severe, brief symptom-free intervals or from 1 to 3 consecutive

4—Extreme, less than 1 consecutive hr/day symptom-free
2. Interference due to Obsessive Thoughts

• How much do these thoughts get in the way of school or doing things
with friends?
• Is there anything that you don’t do because of them?

(If currently not in school determine how much performance would be
affected if patient were in school.)
0—None
1—Mild, slight interference with social or school activities, but overall
performance not impaired
2—Moderate, definite interference with social or school performance,
but still manageable
3—Severe, causes substantial impairment in social or school performance
3. Distress Associated with Obsessive Thoughts

• How much do these thoughts bother or upset you?
(Only rate anxiety/frustration that seems triggered by obsessions, not
generalized anxiety or anxiety associated with other symptoms.)
0—None
1—Mild, infrequent, and not too disturbing
2—Moderate, frequent, and disturbing, but still manageable
3—Severe, very frequent, and very disturbing
4—Extreme, near constant, and disabling distress/frustration
4. Resistance against Obsessions

• How hard do you try to stop the thoughts or ignore them?
(Only rate effort made to resist, not success or failure in actually con-
trolling the obsessions. How much patient resists the obsessions may
or may not correlate with their ability to control them. Note that this item
does not directly measure the severity of the intrusive thoughts; rather
it rates a manifestation of health, i.e., the effort the patient makes to
counteract the obsessions. Thus, the more the patient tries to resist,
the less impaired is this aspect of his/her functioning. If the obsessions
are minimal, the patient may not feel the need to resist them. In such
cases, a rating of ‘0’ should be given.)
0—None, makes an effort to always resist or symptoms so minimal
doesn’t need to actively resist
1—Mild, tries to resist most of the time

2—Moderate, makes some effort to resist
3—Severe, yields to all obsessions without attempting to control them,
but does so with some reluctance
4—Extreme, completely and willingly yields to all obsessions
5. Degree of Control over Obsessive Thoughts

• When you try to fight the thoughts, can you beat them?
• How much control do you have over the thoughts?

(In contrast to the preceding item on resistance, the ability of the
patient to control his/her obsessions is more closely related to the
severity of the intrusive thoughts.)
1—Much control, usually able to stop or divert obsessions with some
effort and concentration
2—Moderate control, sometimes able to stop or divert obsessions
3—Little control, rarely successful in stopping obsessions, can only
divert attention with difficulty
4—No control, experienced as completely involuntary, rarely able to
even momentarily divert thinking
Name ________________________________ Date ____________________________
CY–BOCS Compulsions Checklist

Check all that apply, but clearly mark the principal symptoms with a ‘P’. (Items
marked ‘*’ may or may not be compulsions.)
Current Past Washing/Cleaning Compulsions

____ ____ Excessive or ritualized handwashing
____ ____ Excessive or ritualized showering, bathing, toothbrushing,
grooming, or toilet routine
____ ____ Excessive cleaning of items (e.g. personal clothes or important
items)
____ ____ Other measures to prevent or remove contact with
contaminants
____ ____ Other (describe) _________________________________________
Checking Compulsions
____ ____ Checking locks, toys, school books/items, etc.
____ ____ Checking associated with getting washed, dressed, or
undressed
____ ____ Checking that did not/will not harm others
____ ____ Checking that did not/will not harm self
____ ____ Checking that nothing terrible did/will happen
Appendix 1 207
____ ____ Checking that did not make mistake

____ ____ Checking tied to somatic obsessions
____ ____ Other (describe) _________________________________________
Repeating Compulsions
____ ____ Rereading, erasing, or rewriting
____ ____ Need to repeat routine activities (e.g., in/out door, up/down
from chair)
____ ____ Other (describe) _________________________________________
Counting Compulsions
Objects, certain numbers, words, etc.
____ ____ Other (describe) _________________________________________
Ordering/Arranging Compulsions
Need for symmetry or evening up (e.g., lining items up a certain
way or arranging personal items in specific patterns)
____ ____ Other (describe) _________________________________________
Hoarding/Saving Compulsions
(distinguish from hobbies and concern with objects of monetary
or sentimental value)
____ ____ Difficulty throwing things away, saving bits of paper, string, etc.
____ ____ Other (describe) _________________________________________
Excessive Magical Games/Superstitious Behaviors

(distinguish from age appropriate magical games)
(e.g., array of behavior, such as stepping over certain spots on
a floor, touching an object/self certain number of times as a
routine game to avoid something bad from happening.)
____ ____ Other (describe) _________________________________________
Rituals Involving Other Persons

The need to involve another person (usually a parent) in ritual
(e.g., asking a parent to repeatedly answer the same questions,
making parent perform certain meal time rituals involving
specific utensils.*)
____ ____ Describe ________________________________________________
Miscellaneous Compulsions
____ ____ Mental rituals (other than counting)
____ ____ Need to tell, ask, confess
____ ____ Measures (not checking) to prevent:
harm to self ____; harm to others ____; terrible consequences
____
____ ____ Ritualized eating behaviors*
____ ____ Excessive list making*
____ ____ Need to touch, tap, rub
____ ____ Need to do things (e.g., touch or arrange) until it feels just right*
____ ____ Rituals involving blinking or staring*
____ ____ Trichotillomania (hair pulling)*
____ ____ Other self-damaging or self-mutilating behavior*
____ ____ Other (describe) _________________________________________
Target symptom list for compulsions
Compulsions (Describe, listing by order of severity):

1. _____________________________________________________________________
______________________________________________________________________
2. _____________________________________________________________________
______________________________________________________________________
3. _____________________________________________________________________
______________________________________________________________________
4. _____________________________________________________________________
______________________________________________________________________
Avoidance (Describe any avoidance behavior associated with compulsions; e.g.,
child avoids putting clothes away to prevent start of counting behavior.)
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
Questions on compulsions (items 6–10)
‘I am now going to ask you questions about the habits you can’t stop.’
6a. Time Spent Performing Compulsive Behaviors

• How much time do you spend doing these things?
• How much longer than most people does it take to complete your usual
daily activities because of the habits?
(When compulsions occur as brief, intermittent behaviors, it may be
impossible to assess time spent performing them in terms of total
hours. In such cases, estimate time by determining how frequently they
are performed. Consider both the number of times compulsions are
performed and how many hours of the day are affected.)
• How often do you do these habits?
[In most cases compulsions are observable behaviors (e.g., hand-
washing), but there are instances in which compulsions are not observ-
able (e.g., silent checking).]
0—None
1—Mild, spends less than 1 hr/day performing compulsions or occa-
sional performance of compulsive behaviors
2—Moderate, spends from 1 to 3 hrs/day performing compulsions or
frequent performance of compulsive behaviors
3—Severe, spends more than 3 and up to 8 hrs/day performing com-
pulsions or very frequent performance of compulsive behaviors
Appendix 1 209
4—Extreme, spends more than 8 hrs/day performing compulsions or

near constant performance of compulsive behaviors
6b. Compulsion-Free Interval

• How long can you go without performing compulsive behavior?
[If necessary ask: What is the longest block of time in which (your
habits) compulsions are absent?]
0—No symptoms
1—Mild, long symptom-free interval or more than 8 consecutive
2—Moderate, moderately long symptom-free interval or more than 3
and up to 8 consecutive hrs/day symptom-free
3—Severe, short symptom-free interval or from 1 to 3 consecutive
4—Extreme, less than 1 consecutive hr/day symptom-free
7. Interference due to Compulsive Behaviors

• How much do these habits get in the way of school or doing things with
friends?
• Is there anything you don’t do because of them?
(If currently not in school, determine how much performance would be
affected if patient were in school.)
0—None
1—Mild, slight interference with social or school activities, but overall
performance not impaired
2—Moderate, definite interference with social or school performance,
but still manageable
3—Severe, causes substantial impairment in social or school
performance
8. Distress Associated with Compulsive Behavior

• How would you feel if prevented from carrying out your habits?
• How upset would you become?
(Rate degree of distress/frustration patient would experience if perfor-
mance of the compulsion were suddenly interrupted without reassur-
ance offered. In most, but not all cases, performing compulsions
reduces anxiety/frustration.)
• How upset do you get while carrying out your habits until you are satisfied?
0—None
1—Mild, only slightly anxious/frustrated if compulsions prevented; only
slight anxiety/frustration during performance of compulsions
2—Moderate, reports that anxiety/frustration would mount but remain

manageable if compulsions prevented; anxiety/frustration increases
but remains manageable during performance of compulsions
3—Severe, prominent and very disturbing increase in anxiety/frustra-
tion if compulsions interrupted; prominent and very disturbing
increase in anxiety/frustration during performance of compulsions
4—Extreme, incapacitating anxiety/frustration from any intervention
aimed at modifying activity; incapacitating anxiety/frustration devel-
ops during performance of compulsions
9. Resistance against Compulsions

• How much do you try to fight the habits?
(Only rate effort made to resist, not success or failure in actually con-
trolling the compulsions. How much the patient resists the compulsions
may or may not correlate with his/her ability to control them. Note that
this item does not directly measure the severity of the compulsions,
rather it rates a manifestation of health, i.e. the effort the patient makes
to counteract the compulsions. Thus, the more the patient tries to
resist, the less impaired is this aspect of his/her functioning. If the com-
pulsions are minimal, the patient may not feel the need to resist them.
In such cases, a rating of ‘0’ should be given.)
0—None, makes an effort to always resist or symptoms so minimal
doesn’t need to actively resist
1—Mild, tries to resist most of the time
2—Moderate, makes some effort to resist
3—Severe, yields to almost all compulsions without attempting to con-
trol them, but does so with some reluctance
4—Extreme, completely and willingly yields to all compulsions
10. Degree of Control over Compulsive Behavior

• How strong is the feeling that you have to carry out the habit(s)?
• When you try to fight them what happens?
(For the advanced child ask:)
• How much control do you have over the habits?
(In contrast to the preceding item on resistance, the ability of the
patient to control his/her compulsions is closely related to the severity
of the compulsions.)
1—Much control, experiences pressure to perform the behavior, but
usually able to exercise voluntary control over it
2—Moderate control, moderate control, strong pressure to perform
behavior, can control it only with difficulty
3—Little control, little control, very strong drive to perform behavior,
must be carried to completion, can only delay with difficulty
Appendix 1 211
4—No control, no control, drive to perform behavior experienced as

completely involuntary and overpowering, rarely able to even
momentarily delay activity
11. Insight into Obsessions and Compulsions

• Do you think your concerns or behaviors are reasonable? (Pause)
• What do you think would happen if you did not perform the compulsion(s)?
• Are you convinced something would really happen?
(Rate patient’s insight into the senselessness or excessiveness of
his/her obsession(s) or compulsion(s) based on beliefs expressed at
the time of the interview.)
0—None, excellent insight, fully rational
1—Mild, good insight, readily acknowledges absurdity or excessive-
ness of thoughts or behaviors but does not seem completely con-
vinced that there isn’t something besides anxiety to be concerned
about (i.e., has lingering doubts)
2—Moderate, fair insight, reluctantly admits thoughts or behavior seem
unreasonable or excessive, but wavers; may have some unrealistic
fears, but no fixed convictions
3—Severe, poor insight, maintains that thoughts or behaviors are not
reasonable or excessive, but wavers; may have some unrealistic
fears, but acknowledges validity of contrary evidence (i.e., overval-
ued ideas present)
4—Extreme, lacks insight, delusional, definitely convinced that concerns
and behavior are reasonable, unresponsive to contrary evidence
12. Avoidance
• Have you been avoiding doing anything, going any place, or being
with anyone because of your obsessional thoughts or out of concern
you will perform compulsions? (If yes, then ask:)
• How much do you avoid? (note what is avoided on symptom list)
(Rate degree to which patient deliberately tries to avoid things. Some-
times compulsions are designed to ‘avoid’ contact with something that
the patient fears. For example, excessive washing of fruits and vegeta-
bles to remove ‘germs’ would be designated as a compulsion not as
an avoidant behavior. If the patient stopped eating fruits and vegeta-
bles, then this would constitute avoidance.)
0—None
1—Mild, minimal avoidance
2—Moderate, some avoidance clearly present
3—Severe, much avoidance; avoidance prominent
4—Extreme, very extensive avoidance, patient does almost everything
he/she can to avoid triggering symptoms
13. Degree of Indecisiveness

• Do you have trouble making decisions about little things that other peo-
ple might not think twice about (e.g., which clothes to put on in the
morning, which brand of cereal to buy)?
(Exclude difficulty making decisions which reflect ruminative thinking.
Ambivalence concerning rationally-based difficult choices should also
be excluded.)
0—None
1—Mild, some trouble making decisions about minor things
2—Moderate, freely reports significant trouble making decisions that
others would not think twice about
3—Severe, continual weighing of pros and cons about nonessentials
4—Extreme, unable to make any decisions, disabling
14. Overvalued Sense of Responsibility

• Do you feel overly responsible for what you do and what effect this has
on things?
• Do you blame yourself for the things that are not within your control?
(Distinguish from normal feelings of responsibility, feelings of worth-
lessness, and pathological guilt. A guilt-ridden person experiences
him/herself or his/her actions as bad or evil.)
0—None
1—Mild, only mentioned on questioning, slight sense of over
responsibility
2—Moderate, ideas stated spontaneously, clearly present, patient
experiences significant sense of over-responsibility for events out-
side his/her reasonable control
3—Severe, ideas prominent and pervasive, deeply concerned he/she
is responsible for events clearly outside his control, self-blaming
farfetched and nearly irrational
4—Extreme, delusional sense of responsibility (e.g., if an earthquake
occurs 3,000 miles away patient blames themselves because they
didn’t perform their compulsions)
15. Pervasive Slowness/Disturbance of Inertia

• Do you have difficulty starting or finishing tasks?
• Do many routine activities take longer than they should?
(Distinguish from psychomotor retardation secondary to depression.
Rate increased time spent performing routine activities even when spe-
cific obsessions cannot be identified.)
0—None
1—Mild, occasional delay in starting or finishing tasks/activities
Appendix 1 213
2—Moderate, frequent prolongation of routine activities but tasks usu-

ally completed, frequently late
3—Severe, pervasive and marked difficulty initiating and completing
routine tasks, usually late
4—Extreme, unable to start or complete routine tasks without full
assistance
16. Pathological Doubting

• When you complete an activity do you doubt whether you performed it
correctly?
• Do you doubt whether you did it at all?
• When carrying out routine activities do you find that you don’t trust your
senses (i.e. what you see, hear, or touch)?
0—None
1—Mild, only mentioned on questioning, slight pathological doubt,
examples given may be within normal range
2—Moderate, ideas stated spontaneously, clearly present and apparent
in some of patient’s behaviors, patient bothered by significant patho-
logical doubt; some effect on performance but still manageable
3—Severe, uncertainty about perceptions or memory prominent;
pathological doubt frequently affects performance
4—Extreme, uncertainty about perceptions constantly present; patho-
logical doubt substantially affects almost all activities, incapacitat-
ing (e.g., patient states ‘my mind doesn’t trust what my eyes see’)
17. Global Severity

• Interviewer’s judgement of the overall severity of the patient’s illness.
• Rated from 0 (no illness) to 6 (most severe patient seen).
(Consider the degree of distress reported by the patient, the symptoms
observed, and the functional impairment reported. Your judgement is
required both in averaging this data as well as weighing the reliability
or accuracy of the data obtained. This judgement is based on informa-
tion obtained during the interview.)
0—No illness
1—Slight, illness slight, doubtful, or transient; no functional impairment
2—Mild, little functional impairment
3—Moderate, functions with effort
4—Moderate–severe, limited functioning
5—Severe, functions mainly with assistance
6—Extremely severe, completely nonfunctional
18. Global Improvement

• Rate total overall improvement present since the initial rating whether
or not, in your judgement, it is due to drug treatment.
0—Very much worse
1—Much worse
2—Minimally worse
3—No change
5—Much improved
19. Reliability
Rate the overall reliability of the rating scores obtained. Factors that
may affect reliability include the patient’s cooperativeness and his/her
natural ability to communicate. The type and severity of obsessive-
compulsive symptoms present may interfere with the patient’s concen-
tration, attention, or freedom to speak spontaneously (e.g., the content
of some obsessions may cause the patient to choose his/her words
very carefully).
0—Excellent, no reason to suspect data unreliable
1—Good, factor(s) present that may adversely affect reliability
2—Fair, factor(s) present that definitely reduce reliability
3—Poor, very low reliability
Appendix 1 215
Children’s Yale–Brown Obsessive Compulsive Scale (3/1/90)

CY–BOCS total (add items 1–10) 䊐
Patient name __________________ Date ______________________
Patient ID _____________________ Rater _____________________

1. Time spent on obsessions 0 1 2 3 4
1b. Obsession-free interval No Moderately Extremely

2. Interference from obsessions 0 1 2 3 4

3. Distress of obsessions 0 1 2 3 4
Always Completely
Resists Yields
5. Control over obsessions 0 1 2 3 4
Obsession subtotal (add items 1–5) 䊐

6. Time spent on compulsions 0 1 2 3 4
6b. Compulsion-free interval No Moderately Extremely

7. Interference from compulsions 0 1 2 3 4

8. Distress from compulsions 0 1 2 3 4
Always Completely
Resists Yields
10. Control over compulsions 0 1 2 3 4
Compulsion subtotal (add items 6–10) 䊐
Excellent Absent
11. Insight into O-C symptoms 0 1 2 3 4

12. Avoidance 0 1 2 3 4
13. Indecisiveness 0 1 2 3 4
14. Pathologic responsibility 0 1 2 3 4
15. Slowness 0 1 2 3 4
16. Pathologic doubting 0 1 2 3 4
17. Global severity 0 1 2 3 4 5 6

18. Global improvement 0 1 2 3 4 5 6
19. Reliability: Excellent ⫽ 0 Good ⫽ 1 Fair ⫽ 2 Poor ⫽ 3

Maudsley Obsessive-Compulsive Inventory*

Name _____________________________________ Date _____________________
________________________________________________________________________
INSTRUCTIONS: Please answer each question by putting a circle around the ‘True’ or
the ‘False’ following the question. There are no right or wrong
answers and no trick questions. Work quickly and do not think about
the exact meaning of the question.†
1. I avoid using public telephones because of possible True False

contamination.
2. I frequently get nasty thoughts and have difficulty in True False
getting rid of them.
3. I am more concerned than most people about honesty. True False
4. I am often late because I can’t seem to get through True False
everything on time.
5. I don’t worry unduly about contamination if I touch an True False
animal.
6. I frequently have to check things (e.g., gas or water taps, True False
doors) several times.
7. I have a very strict conscience. True False
8. I find that almost every day I am upset by unpleasant True False
thoughts that come into my mind against my will.
9. I do not worry unduly if I accidentally bump into somebody. True False
10. I usually have serious doubts about the simple everyday True False
things I do.
11. Neither of my parents was very strict during my childhood. True False
12. I tend to get behind in my work because I repeat things True False
over and over again.
13. I use only an average amount of soap. True False
14. Some numbers are extremely unlucky. True False
15. I do not check letters over and over again before mailing True False
them.
16. I do not take a long time to dress in the morning. True False
17. I am not excessively concerned about cleanliness. True False
18. One of my major problems is that I pay too much attention True False
to detail.
19. I can use well-kept toilets without any hesitation. True False
20. My major problem is repeated checking. True False
21. I am not unduly concerned about germs and diseases. True False
22. I do not tend to check things more than once. True False
23. I do not stick to a very strict routine when doing ordinary True False
things.
24. My hands do not feel dirty after touching money. True False
25. I do not usually count when doing a routine task. True False
26. I take rather a long time to complete my washing in the True False
morning.
27. I do not use a great deal of antiseptics. True False
*Reprinted from Behav Res Ther; 15: Hodgson RJ, Rachman S, Obsessional-compulsive
complaints, 389–395, 1977 with permission from Elsevier Science.
†Answers that support a diagnosis of OCD are underlined.
Appendix 1 217
28. I spend a lot of time every day checking things over and True False
over again.
29. Hanging and folding my clothes at night does not take up True False
a lot of time.
30. Even when I do something very carefully I often feel that it True False
is not quite right.
Comprehensive Psychopathological Rating Scale*

Obsessive-Compulsive Disorder Subscale Reported
Psychopathology
Name ________________ Date ____________ Rater __________________
1. Sadness
Representing subjectively experienced mood, regardless of whether it is
reflected in appearance or not. Includes depressed mood, low spirits,
despondency, and the feeling of being beyond help and without hope.
Rate according to intensity, duration, and the extent to which the mood is
influenced by events.
Elated mood is scored 0 on this item.
0—Occasional sadness may occur in the circumstances.
1—Predominant feelings of sadness, but brighter moments occur.
2—Pervasive feelings of sadness or gloominess. The mood is hardly
influenced by external circumstances.
3—Continuous experience of misery or extreme despondency.
2. Inner Tension
Representing feelings of ill-defined discomfort, edginess, inner turmoil,
mental tension mounting to panic, dread, and anguish.
Rate according to intensity, frequency, duration, and the extent of reas-
surance called for.
Distinguish from sadness (1) and worrying (3).
0—Placid. Only fleeting inner tension.
1—Occasional feelings of edginess and ill-defined discomfort.
2—Continuous feelings of inner tension or intermittent panic that the
patient can only master with some difficulty.
3—Unrelenting dread or anguish. Overwhelming panic.
*From Asberg M, Montgomery SA, Perris C, et al: A comprehensive psychopathological

rating scale. Acta Psychiatr Scand (Suppl) 1978; 271:5–9. Used by permission.
http://journals.munksgaard.dk/actapsych.
3. Worrying over Trifles

Representing apprehension and undue concern over trifles, which is diffi-
cult to stop and out of proportion to the circumstances.
Distinguish from inner tension (2), compulsive thoughts (4), and indeci-
sion (6).
0—No particular worries.
1—Undue concern; worrying that can be shaken off.
2—Apprehensive and bothered about trifles or minor daily routines.
3—Unrelenting and often painful worrying. Reassurance is ineffective.
4. Compulsive Thoughts
Representing disturbing or frightening thoughts or doubts that are experi-
enced as silly or irrational but keep coming back against one’s will.
Distinguish from worrying (3).
0—No repetitive thoughts.
1—Occasional compulsive thoughts that are not disturbing.
2—Frequent disturbing compulsive thoughts.
3—Incapacitating or obnoxious obsessions occupying one’s entire
mind.
5. Rituals
Representing a compulsive repeating of particular acts or rituals that are
regarded as unnecessary or absurd and resisted initially but cannot be
suppressed without discomfort.
The rating is based on the time spent on rituals and the degree of social
incapacity.
0—No compulsive behavior.
1—Slight or occasional compulsive checking.
2—Clear-cut compulsive rituals that do not interfere with social
performance.
3—Extensive rituals or checking habits that are time consuming and
incapacitating.
6. Indecision
Representing vacillation and difficulty in choosing between simple
alternatives.
Distinguish from worrying (3) and compulsive thoughts (4).
0—No indecisiveness.
1—Some vacillation but can still make a decision when necessary.
2—Indecisiveness or vacillation that restricts or prevents actions,
makes it difficult to answer simple questions or make simple
choices.
Appendix 1 219
3—Extreme indecisiveness even in situations where conscious deliber-

ation is not normally required, such as whether to sit or stand, enter
or stay outside.
7. Lassitude
Representing difficulty getting started or slowness in initiating and per-
forming everyday activities.
Distinguish from indecision (6).
0—Hardly any difficulty in getting started. No sluggishness.
1—Difficulties in starting activities.
2—Difficulties in starting simple routine activities, which are carried out
only with effort.
3—Complete inertia. Unable to start activity without help.
8. Concentration Difficulties
Representing difficulties in collecting one’s thoughts amounting to inca-
pacitating lack of concentration.
Rate according to intensity, frequency, and degree of incapacity
produced.
0—No difficulties in concentrating.
1—Occasional difficulties in collecting one’s thoughts.
2—Difficulties in concentrating and sustaining thought that interfere
with reading and conversation.
3—Incapacitating lack of concentration.
NIMH Global Obsessive-Compulsive Scale*
DIRECTIONS: Choose the number (1 to 15) that best describes the present
clinical state of the patient based on the guidelines below:
1–3 Minimal within range of normal. Mild symptoms. Person
spends little time resisting them. Almost no interference in
daily activity.
4–6 Subclinical obsessive-compulsive behavior. Mild symptoms
that are noticeable to patient and observer, cause mild inter-
ference in patient’s life and which he or she may resist for a
minimal period of time. Easily tolerated by others.
7–9 Clinical obsessive-compulsive behavior. Symptoms that cause
significant interference in patient’s life and which he or she
spends a great deal of conscious energy resisting. Requires
some help from others to function in daily activity.
*From Insel TR, Murphy DL, Cohen RM, et al: Arch Gen Psychiatry 1983; 40:605–12. Copy-
righted (1983), American Medical Association.
10–12 Severe obsessive-compulsive behavior. Symptoms that are

crippling to the patient, interfering so that daily activity ‘an
active struggle.’ Patient may spend full time resisting symp-
toms. Requires much help from others to function.
13–15 Very severe obsessive-compulsive behavior. Symptoms that
completely cripple patient so that he or she requires close
staff supervision over eating, sleeping, etc. Very minor deci-
sion making or minimal activity require staff support. ‘Worst
I’ve ever seen.’
Clinical Global Impairment Scale
Considering your total clinical experience with this particular problem,

how mentally ill is the patient at this time? Circle one (most appropriate).
1—Normal, not at all ill
2—Borderline mentally ill
3—Mildly ill
4—Moderately ill
5—Markedly ill
6—Severely ill
7—Among the most extremely ill
Clinical Global Improvement Scale
Compared to the patient’s condition at the beginning of treatment, how

much has he/she changed? Circle one (most appropriate).
2—Much improved
4—No change
5—Minimally worse
6—Much worse
7—Very much worse
Source: National Institute of Mental Health (public domain).

Appendix 2: Consumer organizations
involved in OCD
Australia France
Anxiety Disorders Foundation of Association Francaise de
Australia Personnes souffrant de Troubles
PO Box 6198 Obsessionnels et Compulsifs
Shopping World, NSW 2060 (AFTOC)
Tel: +0061 (0)16 282 897 E-mail: [email protected]
Web: www.cpod.com/monoweb/
Obsessive Compulsive and Anxiety aftoc
Disorders Foundation of Victoria
(Inc) Association Francaise Des Tocs et
PO Box 358 Du Syndrome Gilles de la Tourette
Mt Waverley 24, Rue Leon Gambetta
Victoria 3149 59790 Ronchin
Australia France
Obsessive Compulsive Disorders

Italy
Support Service
Room 318 GIDOC (gruppo italiano per il
Epworth Building disturbo ossessivo-compulsivo)
33 Pirie Street Corso Vittorio Emanuele 76
Adelaide 10121 Torino
SA 5000 Tel/Fax: +39 011 517 5239
Australia
IDEA (istituto per la depressione
e l’ansia)
Canada Via Statuto 8
20121 Milano
Obsessive-Compulsive Disorder
Tel: +39 02 654 126
Network (OOCDN)
Fax: +39 02 654 716
PO Box 151
Etobicoke
Ontario
Canada
221
South Africa UK
OCD Association of South Africa First Steps to Freedom
PO Box 87127 7 Avon Court
Houghton 2041 School Lane
South Africa Kenilworth
Tel: +0027 (0)11 881 3678 CV8 2GX
Tel: +44 01926 864473
Depression and Anxiety Support
Group Obsessive Action
Suite 209, 2nd Floor Unit 108
Benmore Gardens Aberdeen Centre
Greystone Drive 22-24 Highbury Grove
Benmore 2196 London, N5 2EA
South Africa Tel: +44 (0)20 7226 4000
Tel: +0027 (0)11 884 1797 Fax: +44 (0)20 7288 0828
E-mail: admin@obsessive-
Mental Health Information Centre action.demon.co.uk
(and MRC Unit on Anxiety Web: www.obsessive-
Disorders) action.demon.co.uk
PO Box 19063
Tygerberg 7505
USA
South Africa
Tel: +0027 (0)21 938 9229 OC Foundation, Inc
337 Notch Hill Road
North Branford, CT 06471
South America
Tel: +1 203 315 2190
Asociado De Portadores De Fax: +1 203 315 2196
Sindrome De Tourette E-mail: [email protected]
Tiques E Trastornos Obsessivo Web: www.ocfoundation.org
Compulsivo
Trichotillomania Learning Center
Rua Drive Ovidio Pires De Silvia
1215 Mission St, Suite 2
Arias
Santa Cruz, CA 95060
Campos
Tel: +1 831 457 1004
S/N Sala 4025
Fax: +1 831 426 4383
Sao Paolo
Brazil
Web: www.trich.org
Tel: +0055 11 280 9198
Anxiety Disorders Association of
America
11900 Parklawn Drive, Suite 100
Rockville, MD 20852
Tel: +1 301 231 9350
Fax: +1 301 231 7392
Web: www.adaa.org
Index
Page numbers in italic denote figures and tables where there is no textual reference to the
material on the same page.
OCD = obsessive compulsive disorder.
abstract symptoms 44–5 cAMP-response element binding protein

addictive behaviours 30 92–3
adolescents 8, 153–62 candidate gene studies 70–1
see also children; young people caudate 29, 39, 95, 155
affect regulation 30 cognitive-behavioural therapy 128
affective-motivational circuit 32 imaging 79, 80
age at OCD onset 4, 5–6, 66, 154 cerebrospinal fluid studies 89, 94
aggressive obsessions 19, 170, 186, challenge tests 81–2, 91, 93
202–3 checking compulsions 18, 19, 187, 206–7
American Psychiatric Association 2 children
amygdala 78 and clomipramine 105
amygdala–hippocampus circuit 42 drug efficacy/tolerability 110
anatomy, functional, of OCD 78–9 with OCD 4, 8, 18, 153–62
animal stereotypies 42 in family studies 66
anthropophobia 41 immunology 94, 95
antidepressants 26, 92 OCD symptoms 44, 45
antiobsessional drugs 26, 110, 158 and trichotillomania 27
antipsychotic drugs 39, 103, 140–2 see also adolescents; young people
anxiety 26, 81, 139 Children’s Yale–Brown Obsessive
disorders 62–3, 77, 154, 161 Compulsive Scale 200–15
Anxiety Disorders Interview Schedule 16 checklists 202–3, 205–6
approach/avoidance continuum 24 2-chloro-6(-1-piperazinyl)pyrazine 91
arginine vasopressin 70, 94 cingulate lobe 78, 79, 83, 156
Asperger’s syndrome 23, 45 citalopram 89, 106, 107, 158
assessment dosage 108, 109, 136
of harm 38, 168 classification 2–3
of OCD 15–20 of jealousy 43–4
augmented feedback 179–80 of repetitive behaviours 25
autoimmunity 94, 156, 171 cleaning/washing obsessions 18, 187
avoidance 17, 195, 204, 211 Clinical Global Impairment Scale 220
awareness of OCD 10, 11 Clinical Global Impressions Scale 17, 135,
185
basal ganglia 37, 82, 93, 123 Clinical Global Improvement Scale 220
pathology 41, 46, 77, 94, 171 clomipramine 80, 83, 89, 91, 103, 104–5
baseline level of impairment 15, 16 [3H]-imipramine binding 90
behaviour therapy 108, 119, 170, 171 antiobsessional effect 119
behavioural challenge 81–2 in combination therapy 137, 139–40, 143
benzodiazepines 103 discontinuation studies 112, 113
body dysmorphic disorder 6, 39–40, 41 dosage/route 108, 113, 136
co-transmitted with OCD 25 and exposure therapy 126
by proxy 44 and neuropeptide levels 94
and stereotypies 42 side effects 107, 140, 158
borderline personality disorder 46 and Tourette’s syndrome 26
bradykinesia 46 and trichotillomania 27
bradyphrenia 46 vs cognitive-behavioural therapy 159
bromocriptine 142 vs SSRIs 105, 106
buspirone 91, 114, 138 in young people 158
clonazepam 113, 138–9 diacylglycerol 92

clonidine 93 diagnoses 2–3
clorgyline 114 differential 16, 184
clozapine 141 of OCD 6, 8, 15, 41
cognitive interventions 120, 121–4 Diagnostic and Statistic Manual
cognitive model of OCD 122, 170 Axis I disorders 8
cognitive phenomena 26 Axis II disorders 8
cognitive processes vs stimulus–response DSM-III 3, 61, 62, 66, 68
links 180 DSM-IV 2, 6, 9, 40, 68
cognitive restructuring 120, 124 on stereotypic movement disorder 42
cognitive-behavioural theory 122 and trichotillomania 27
cognitive-behavioural therapy 119, 123, Diagnostic Interview Schedule (DIS) 3, 61
170, 173 diagnostic specifiers 9
and caudate activity 128 diagnostic tools 15–29
and drug therapy 126–7, 171 diary keeping 122
multimodal 124–5, 127 direct interview method 64, 65–8
and unusual symptoms 44, 45 discontinuation studies 111, 112, 113
vs clomipramine 159 disinhibition 169, 170
in young people 159, 160 dopamine 28–31, 93
cognitive-biobehavioural self-treatment 123 dopamine antagonists 27, 39
combination therapies 126–7, 136–40, 142, dopamine pathways 28–31
143, 158, 171–2 dopamine receptor antagonists 170
comorbid depression 108, 139, 145 in combination therapy 137, 140, 158
comorbid tics 154, 158 dopaminergic systems 27, 28, 39, 70
comorbidity 8–10, 55 and OC spectrum disorder 32
Comprehensive Psychopathological Rating and Tourette’s syndrome 39
Scale 217–19 dorsal cognitive circuit 31
compulsions dosage 158
definition 2, 25–6, 183–4, 201 dose titration 110
examples 184, 201 doubt, pathological 17, 18, 24, 196–7,
familial risk 68 213
misdiagnosis 15 drug effect characteristics 105
compulsive behaviours 192–4, 208–11 drug therapy
compulsive thoughts 218 and cognitive-behavioural therapy 126–7
compulsivity/impulsivity dimension 24 combination 136
computerized tomography 80, 155 dosage 108, 110, 158
concentration difficulties 219 duration 105, 110, 111, 113
concordance in OCD 61, 62, 63 in young people 158
consumer organizations 221–2 integrated approach 173
contamination obsessions 186, 202 long term efficacy 110–11
continuation/discontinuation studies novel compounds 143–5
110–11, 112, 113 with psychotherapy 171
core features of OCD 24 side effects 107, 110, 140, 144, 158
core psychobiological deficit 167, 168 in young people 157
corticostriatal pathways 31, 32, 79
corticostriatal–thalamic–cortical (CSTC) efficacy studies 110
circuits 37, 167–8, 170 egodystonicity 2, 44
costs, economic 3, 54–5, 125 egosyntonicity 9
counting compulsions 188, 207 electroconvulsive therapy 103, 145
culture-bound syndromes 40–1 encephalitis lethargica 78
cyclic AMP pathway 92 Epidemiological Catchment Area studies 3,
cytokines 95 54, 67
epidemiology 3–4, 154–5, 170
depersonalization 42 OCD and OCPD 9–10
depression 8, 79 OCD in young people 153
comorbid 108, 139, 145 epilepsy 77
dermatological problems 10 EuroQoL 58
desensitization/reinforcement 119 exposure/response prevention 119, 120–2,
desipramine 27, 89, 143, 158 126
diabetes insipidus 78 vs rational emotive therapy 123–4
Index 225
factor analyses 9, 38 hormonal system 28

familial aggregation 63–4 human capital methodology 54
familial factors 5 5-hydroxyindoleacetic acid 89
family assessment studies 56 hyperserotonergic function 169
family history method 64–5, 66, 67, 68 hypochondriacal obsessions 10
family involvement 44, 159, 173 hypochondriasis 6, 40
family relationships 55–7, 125
family studies 25, 63–8, 155 imaginal exposure 120, 124
family study method see direct interview imaging 79–80, 81, 82–3, 155, 168
method and behavioural challenge 81–2
family-based association study 70 [3H]-imipramine binding 89, 90
fenfluramine 137 immunological alterations 94–5
flooding 120 improvement 197, 214
Florida Obsessive Compulsive Inventory impulsive symptoms 26, 43
(FOCI) 18 incompleteness 24
fluoxetine 106, 107, 158 indecisiveness 17, 195, 212, 218–19
in combination therapy 138, 139,
139–40, 143 inositol 143–4
discontinuation studies 112, 113 insight 6, 17, 39, 194–5
dosage 108, 109 lack of 45, 46
and exposure therapy 127 personal 177–8
and SPET imaging 82 instrumental role functioning 53
and Tourette’s syndrome 26 integrated therapy 170–4
and trichotillomania 27 International Classification of Diseases 2
flutamide 144–5 interpersonal symptoms 43–4
fluvoxamine 89, 106, 107 intracellular mechanisms 92
combination therapies 141, 171–2 ipsapirone 91
dosage 108, 113 isolation 179
efficacy/tolerability studies 110
and exposure therapy 127 jealousy 43–4
follow-up studies 5, 6, 161
functional analysis of symptoms 125 koro 40–1
future research 57, 71, 128
lassitude 219
gabapentin 143 Lehman’s Quality of Life scale 54, 57
gamma knife capsulotomy 146 leucotomy 79
gender 4–5, 6, 154, 161 Leyton Obsessional Inventory 19, 63, 65
generalized anxiety disorder 62 limbic system 78, 83
genetic factors in OCD 61–71 lithium 103, 136, 137–8
Gilles de la Tourette’s syndrome see loop tapes 121, 122
Tourette’s syndrome
group therapy 125–6 magic/superstitious behaviours 207
guided recovery 122 magic/superstitious obsessions 203
magnetic resonance imaging 80
5-HT and behavioural challenge 81–2
receptor 91, 92 magnetic resonance imaging studies,
transporter 89–90, 92 morphometric 29
uptake/reuptake 90, 92 magnetic resonance morphologic study
5-HT1Dß autoreceptor gene 70–1 155
habituation 120 major depressive disorder 138
haloperidol 27, 141 malignant OCD 5
Hamilton Depression Rating Scale 53, 144 marital relationships 55–7, 125
health care, non-psychiatric 10, 11 Maudsley Obsessional Compulsive
health-related quality of life 51, 52, 53, 54 Inventory 18–19, 216–17
heritability 61–2, 63 Medical Outcomes Study 53, 54, 57
heterogeneity of OCD 23, 70, 93 mesocortical pathway 28, 29, 30
hippocampal lesions 78 mesolimbic pathway 28, 29, 30
hoarding compulsions 19, 39, 188, 207 mesolimbic system dysfunction 83
hoarding obsessions 186, 203 methylchlorophenylpiperazine 42, 91, 92
homogeneity of OCD 37 Mexican Institute of Psychiatry 67
mianserin 113 olanzapine 142

mixed model of inheritance 70 olfactory reference syndrome 40
monoamine oxidase inhibitors 103, 114 ondansetron 91
mood disorders 154, 161 onychophagia 23, 31
motivation for behavioural change 125 opioid system 28, 70, 94
movement disorders 77 orbitofrontal cortex 79
multiple chemical sensitivity 40 ordering/arranging compulsions 188, 207
musical symptoms 41 oxytocin 70, 94
National Institute of Mental Health 3 Padua Inventory 19

Global Obsessive-Compulsive Scale Paediatric Autoimmune Neuropsychiatric
219–20 Disorders Associated with
study of childhood OCD 66 Streptococci (PANDAS) 95, 156,
negative feedback loops 56–7 171
neostriatal hypothesis 79, 83 paradoxical intention 119
neuroanatomy 77–83 parallel processes of control theory 180
neurochemical abnormalities 169 parietal lobe 83
neuroimaging research 123, 155, 156 Parkinson’s disease 77
neuroleptics 26, 90 [3H]-paroxetine binding 90
neurological dysfunction 77 paroxetine 89, 105, 106, 107, 158
neuropeptides 94 discontinuation studies 112, 113
neurosurgery 77, 146 dosage 108, 109
neutralizing behaviours 121 pathogenesis 155–6
nigrostriatal pathway 28, 29–30 pathophysiology 89–97
noradrinergic system 93–4, 95 patients’ perspectives 177–81
and affect regulation 30 pharmacological responses 90, 104
and OC spectrum disorder 32 pharmacological therapy see drug therapy
norepinephrine system 28, 30, 32 phenelzine 114
Nottingham Health Profile 58 phenomenological analysis 7
nucleus accumbens 30 phobias 6
phosphatidylinositol pathway 92
obsessional thoughts 6, 19, 177, 189–91, pimozide 27, 140–1
204–6 pindolol 137, 139
assessment 19 platelet serotonin concentrate 158
cognitive therapy 121–2 platelet serotonin transporter 155
triggering 181 platelet studies 89–90
obsessions 2, 183, 184, 200, 201 platelet sulfotransferase 93
familial risk 68 POINTER 70
misdiagnosis 15 positron emission tomography 79–80
obsessive compulsive disorder 2, 37–8, and behavioural challenge 81
178 post-traumatic stress disorders 168
caudate dysfunction 29 differential diagnosis 41–2
cognitive model 122 pregnancy 5
comorbid 55 prevalence of OCD 3
comorbid tics 26, 38–9, 103, 158 procedural knowledge/strategies 167, 168
mesolimbic system dysfunction 30 prognosis of OCD 5–6, 10
neuropsychiatric features 77–8 protein kinases 92, 93
refractory 135–47 psilocybin 90
segregation analyses 69–70 psychoanalytical theory 9
and Tourette’s syndrome 38 psychodynamic theories 169
in young people 153–61 psychodynamic therapy 119, 159
Obsessive Compulsive Foundation 52, 54, psychoeducation 172, 173
56 psychopharmalogical treatment 156–8
obsessive compulsive personality disorder psychosocial costs 3
9–10, 23–33 psychosurgery 78–9
conceptualizations 24–5 psychotherapy 119–29, 171
and OCD 25 puerperium 5
Obsessive-Compulsive Disorder putamen
Association of South Africa 52 and OCD imaging 80
oculomotor circuit 31 and Tourette’s syndrome 29, 39
Index 227
quality of life 51–8 sensorimotor circuit 31

as culturally bound concept 51 sensory phenomena 26
and discontinuation studies 113 sensory symptoms, unusual 41–2
Quality of Life Research 51 septo-hippocampal system 78
Quality of Well-Being Scale 58 serotonergic medication 170
questionnaires 51, 52, 53 serotonergic systems 27, 28, 37–8
and affect regulation 30
rating instruments 16–17, 183–220 genetic factors 70
rational emotive therapy 123–4 and OC spectrum disorder 32
rCBF 81, 82, 83 serotonin 31–2, 89–93, 104
refractory OCD 135–47 serotonin reuptake inhibitors (SRIs) 27, 39,
drug studies 144 103, 156
integrated approach 173 with behaviour therapy 171
regional cerebral metabolic rate 79, 80 in combination therapy 137, 138, 139
regressive logistic models 69 high dose 136
relapse 111, 112, 113 in jealousy 44
combination therapies 127 lack of response 113
exposure/response prevention 120 and personality disorders 127
and integrated therapy 172 and tic-related OCD 26
relationships 55–7 and trichotillomania 27
reliability and unusual symptoms 41, 42, 45
of diagnostic tools 16, 19 see also selective serotonin reuptake
of rating scores 197–8, 214 inhibitors (SSRIs)
religious obsessions 45, 187, 203 sertraline 89, 105, 106, 107
repeating rituals 187, 207 discontinuation studies 112, 113
repetitive behaviors dosage 108, 109, 136
classification 25 efficacy/tolerability studies 110–11
preceding phenomena 26 sexual behaviour, compulsive 31
repetitive transcranial magnetic stimulation sexual obsessions 186, 203
146 short-term interventions 128
resistance 184 side effects see under drug therapy
to compulsions 193–4, 210 single photon emission computed
to obsessions 2, 190, 205–6 tomography 41, 81, 82–3
responsibility, pathological 17, 195–6, 212 skin-picking 28, 31
rheumatic fever 94, 95 slowness 17, 18, 196, 212–13
risk assessment, abnormal 24 obsessional 45–6, 79
risk-taking 43 Social Adjustment Scale 58
risperidone 27, 90, 141–2 social anxiety disorder 41
rituals involving other persons 207, 218 social impairment 11
social relationships 53
sadness 217 socioeconomic effects 54–5
schizophrenia 10, 30, 46 somatic manifestations 10, 39–40
schizotypal personality disorder (SPD) 10 somatic obsessions 187, 203
screening for OCD 11 somatostatin 94
Screening Test for Obsessive-compulsive spectrum of OCD-related disorders 2
Problems (STOP) 18 stalking 44
scrupulosity 45, 187, 203 stereotypic movement disorder 42
segregation analyses 69–70 stereotypic symptoms 42–3
selective serotonin reuptake inhibitors stimulus–response links vs cognitive
(SSRIs) 89, 90, 92, 103 processes 180
in combination therapy 139–40, 158 streptococci and OCD 94, 95, 156, 171
lack of response 93 striatal dopaminergic function 79
and neuroleptics 127 striatal seratonergic hypofunction 169
side effects 107 striatum optimization/protection 170–1
symptom reduction 119 Structural Clinical Interview for DSM-IV
vs behavioural therapy 170 16
vs clomipramine 105, 106, 107 subclinical OCD 4, 45
in young people 158 subcortical dementia 46
see also serotonin reuptake inhibitors subjective experience, classification of
self-mutilation 23, 40 25
subtypes in practice 172–4

of OCD 6, 23–4 promising 145
tic-related subtype 25–8 and quality of life 54
of Tourette’s syndrome 9 of family 56
suicidal behaviour 8, 55 trichotillomania 6, 27–8, 31, 42
sumatripan 145, 168 by proxy 44
sumatriptan 91 putamen dysfunction 29
support groups 173 tricyclic antidepressants 103
Sydenham’s chorea 23, 77, 94, 156 triiodothyronine 143
symmetry/exactness obsessions 187 tryptophan 113, 137
symptom clusters tuberoinfundibular pathway 28, 29, 30–1
OCD 18 twin studies 61–3
Tourette’s syndrome 9
symptom severity 17, 80, 185, 197, 213 unemployment 54, 55
symptom specificity 201
symptom-directed interventions 124, 125 venlafaxine 27
symptoms of OCD 6, 37–8 ventral cognitive circuit 31–2
with tics 38 vocational functioning, impaired 52–3
taijin kyofusho 41 washing/cleaning compulsions 19, 206

tension 217 WHOQOL 58
therapists, lack of 125 withdrawal effects 111
thermocapsulotomy 146 Work and Social Adjustment Scale 58
tic disorders 25–8, 161 World Health Organization 3
and combination therapies 141, 142 International Classification of Diseases
comorbid 154 2
misdiagnosis 15 quality of life questionnaire 51
tic rating instrument 184 worrying 177, 218
tic-related OCD 25–8, 78
tics xenon 133 inhalation 81
definition 26
drug therapy 140 Yale–Brown Obsessive Compulsive Scale
segregation analyses 69 (Y–BOCS) 17–18, 53, 54, 183–215
and stereotypies 42 caudate activity 128
tolerability studies 110 checklists 186–8
Tourette’s syndrome 5, 9, 23, 25–8, 78 combination therapies 127, 172
and noradrenaline 94 general instructions 183–5
as OC spectrum disorder 28 and improvement 110, 135, 139, 144
and OCD 38 individual vs group therapy 126
putamen dysfunction 29 and rCBF 83
segregation analyses 69 young people
in young people 155 cognitive-behavioural therapy 159, 160
tramadol 94, 144 drug therapy 157, 158
transmission disequilibrium tests 70–1 OCD 153–6
treatment outcome predictors 127–8, 161 outcome of OCD 161
treatment/s psychopharmalogical treatment 156–8
early approaches 119–20 Tourette’s syndrome 155
integrated approach 170–4 see also adolescents; children

Untitled

Uploaded by

Copyright:

Available Formats

Untitled

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Untitled

Uploaded by

Copyright:

Available Formats

Obsessive Compulsive Disorder:

Naomi Fineberg MA(Cantab), MBBS MRCPsych

Dan J Stein BSc (Med), MBChB, FRCPC

First published in the United Kingdom in 2001

Tel.: +44 (0) 20 74822202

This edition published in the Taylor & Francis e-Library, 2003.

ISBN 0-203-21289-4 Master e-book ISBN

ISBN 0-203-27007-X (Adobe eReader Format)

Distributed in the USA by

Distributed in the rest of the world by

Composition by Wearset, Boldon, Tyne and Wear

1 Obsessive compulsive disorder: a 1

3 Obsessive compulsive spectrum 23

4 Unusual symptoms of OCD 37

5 OCD and quality of life 51

6 The role of genetic factors in OCD 61

7 The neuroanatomy of OCD 77

9 Practical pharmacotherapy 103

10 Psychotherapy in OCD 119

11 Treatment of refractory OCD 135

12 OCD in children and adolescents 153

13 An integrated approach to the 167

14 Patients’ perspectives on OCD 177

Appendix 1: Major rating scales 183

Appendix 2: Consumer 221

In memory of Sidney Fineberg, and with grateful thanks to my mentors,

Andreas Broocks MD, PhD Toby D Goldsmith MD

David Cohen MD Wayne K Goodman MD

Peter Farvolden PhD Brian Harvey BPharm, BPharm (Hons),

James V Lucey MD, PhD, MRCPsych, FRCPI David L Pauls PhD

Christopher J McDougle MD Ann Roberts MA(Cantab), MBBS MRCGP

Frederick Toates Dphil, DSc Kelda H Walsh MD

Obsessive compulsive disorder is now recognized as one of the most

NF, DM, DJS

Naomi Fineberg and Ann Roberts

MACBETH: How does your patient, doctor?

(From Shakespeare’s Macbeth, act V scene III; circa 1606)

Throughout history, our conceptualization of obsessive compulsive disor-

Table 1.1 ICD-10 criteria for OCD.

B Obsessions (thoughts, ideas or images) and compulsions share the following

body dysmorphic disorder, trichotillomania, tic disorders and deperson-

How common is OCD?

After the pioneering epidemiological catchment area (ECA) studies car-

Table 1.2 Prevalence of OCD reported by the NIMH epidemiological

Lifetime (%) 6 months (%)

Major depression 5.2 2.9

OCD and gender

Obsessive compulsive disorder is more common in women, although the

Obsessive compulsive disorder is considered to be one of the most

Course and prognosis

particularly in males, having both obsessions and compulsions or magi-

Symptoms and subtypes

Most patients suffer a mixture of different obsessions or compulsions.

Mild forms of obsessional behaviour, such as repetitive checking or

Behaviours Mental acts

Contamination fears (45%) Checking (63%) Covert counting (36%)

Multiple obsessions (60%) Multiple compulsions (48%)

Adapted from Rasmussen and Eisen.20

made if there are also unrelated obsessive-compulsive symptoms, in

Table 1.4 Comorbidity in OCD.