Drug-Induced Movement Disorders

Katherine L. Claxton, PharmD, Jack J. Chen, PharmD, BCPS, CGP,

and David M. Swope, MD

Drug-induced movement disorders (DIMDs) pose a signifi- exposure. The DIMDs of akathisia, tardive dyskinesia,
cant burden to patients, often resulting in nonadherence, dystonia, and parkinsonism are reviewed. Their epidemi-
disease relapse, and decreased quality of life. Dopamine- ology, mechanism, clinical presentation and differential
receptor blocking agents such as conventional antipsy- diagnosis, risk factors, morbidity and mortality, and pre-
chotics (eg, haloperidol and chlorpromazine) and vention and management are discussed. For many of these
antiemetics (eg, metoclopramide and prochlorperazine) disorders, treatment inconsistently provides benefit, and
are most commonly implicated. DIMDs can be categorized therefore, primary prevention is essential. Clinicians and
by the onset of symptoms: acute reactions occurring hours other healthcare professionals play a key role in the iden-
to days after exposure, subacute DIMDs appearing within tification of patients with DIMDs, or those at risk, and in
weeks, and tardive occurring months to years after drug implementing prevention and treatment plans.

KEY WORDS: Akathisia, dystonia, movement disorders, parkinsonism, tardive dyskinesia.

INTRODUCTION medical conditions that should be considered in

the differential diagnosis; however, with a careful
The term drug-induced movement disorder (DIMD) drug history, recognition of DIMDs may be relatively
is a rubric that refers to a variety of phenomenologi- straightforward, as in the case of a patient with a
cally distinct, treatment-emergent, involuntary motor history of DRBA treatment presenting with classic
symptoms, including akathisia, dyskinesia, dystonia, symptoms of tardive dyskinesia (TDk). As with idio-
and parkinsonism. DIMDs, also pervasively referred to pathic movement disorders, anxiety and stress will
as extrapyramidal adverse reactions, remain a signifi- also exacerbate the symptoms that are associated
cant iatrogenic burden among selected patient pop- with DIMDs.
ulations (eg, patients receiving psychotropics for
psychiatric disorders and antiemetics for gastrointesti- DRUGS AND MECHANISMS
nal disorders).
DIMDs generally do not affect mortality, except in Common agents implicated in drug-induced
the rare cases of laryngeal spasm or status dystoni- akathisia, dyskinesia, dystonia, and parkinsonism are
cus; however, the most significant effect of DIMDs is listed in Tables 2 through 5. Neuroleptics, which block
on medication adherence and quality of life. This dopamine receptors in the striatum (eg, haloperidol,
may result in noncompliance and subsequent relapse
and rehospitalization.1 Symptoms of DIMDs interfere
with social functioning, interpersonal communica- To whom correspondence should be addressed: Jack J. Chen,
tion, and performance of motor tasks and activities of PharmD, BCPS, CGP, Loma Linda University, 11262 Campus
daily living. Street, West Hall, Loma Linda, CA 92350. E-mail: [email protected].
Often underrecognized, DIMDs are most com- Katherine L. Claxton, PharmD, clinical pharmacist, Aurora Sinai
monly associated with the use of dopamine-receptor Medical Center, Department of Pharmacy, 945 N State St, Milwaukee,
blocking agents (DRBAs) such as antipsychotics (eg, WI 53233.
fluphenazine and haloperidol) and antiemetics (eg, Jack J. Chen, PharmD, BCPS, CGP, associate professor (neurology),
metoclopramide and prochlorperazine).2 The onset of Schools of Medicine and Pharmacy, Loma Linda University,
DIMDs can be classified as acute (ie, occurring within 11262 Campus St, West Hall, Loma Linda, CA 92350.
hours to days after exposure), subacute (ie, occurring David M. Swope, MD, associate professor of neurology, Depart-
weeks after drug exposure), and tardive (ie, occurring ment of Neurology and School of Medicine, Loma Linda Univer-
months to years after drug exposure). sity, Loma Linda, CA 92350.
The symptomatology of DIMDs (Table 1) is often JOURNAL OF PHARMACY PRACTICE 2007. 20;6:415–429
indistinguishable from the idiopathic form of the con- © 2007 Sage Publications
dition. Additionally, DIMDs may resemble several DOI: 10.1177/0897190007310514

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 CLAXTON ET AL

Table 1
Signs and Symptoms Associated With Drug-Induced Movement Disorders

Drug-Induced Movement Disorders Signs and Symptoms

Akathisia Subjective feeling of restlessness and need to move. Objective symptoms of pacing,
walking in place, foot or toe tapping, and rocking while seated. Distress if restrained or
unable to move. Symptoms may improve during sleep or in a supine position.
Dyskinesia Abnormal involuntary choreoathetoid movements affecting the orofacial region and
tongue. Less commonly affected areas include the extremities and trunk. Lip smacking,
chewing movements, and tongue protrusion are common. Symptoms are not painful but
may result in embarrassment in social settings and difficulty with chewing, speech, and
swallowing.
Dystonia Sustained involuntary muscular contractions or spasms resulting in abnormal postures or
twisting and repetitive movements. Affected body parts include the back, neck, upper
and lower extremities, jaw, and larynx. Symptoms are associated with distress. Pain may
or may not be present. Difficulty with ambulation, breathing, head turning, speech,
and swallowing may occur.
Parkinsonism Tremor, rigidity, and slowness of movement affecting bilateral upper and lower extremities
and truncal regions. Difficulty rising from a seated position, gait imbalance, masked
facies, micrographia, slow shuffling gait, and stooped posture may be observed.

phenothiazine antipsychotics), are the drugs most D2 receptor occupancy rate less than 70% was not
commonly associated with various DIMD phenotypes. associated with EPS, occupancy of 70% to 80%
The term neuroleptics actually translates to “seize the increased the likelihood of EPS, and occupancy above
nerves.”3 The dose of conventional neuroleptics that is 80% was associated with a high percentage of EPSs
associated with antipsychotic effects is similar to that clinically.6 This finding is substantiated by the fact
which produces extrapyramidal symptoms (EPSs). In that an 80% loss of nigrostriatal dopamine receptors
contrast, atypical antipsychotics generally produce results in the classic motor symptoms of Parkinson’s
antipsychotic effects at doses lower than that required disease.
to induce EPSs (Table 6); therefore, although atypical The pharmacodynamic properties of clozapine
antipsychotics may induce movement disorders, the and quetiapine prohibit these agents from reaching
risk is significantly lower as compared with the con- the threshold of 70% at any dose. Positron emission
ventional neuroleptics. Atypical antipsychotics may topography and single photon emission computer-
be preferred over conventional neuroleptics because ized tomography studies have shown that clozapine
of the lower risk of DIMDs; however, the risks of devel- and quetiapine have the lowest striatal D2 receptor
oping metabolic adverse effects (ie, weight gain and occupancy rates and that haloperidol has the high-
glucose intolerance) must be considered. Antiemetics est.7 Based on clinical data in patients with parkin-
that block central dopamine receptors (ie, droperidol, sonism, these agents appear to have the lowest risk
metoclopramide,4 and prochlorperazine) are also com- of worsening motor symptoms of parkinsonism.8,9
monly implicated in the various DIMDs, particularly Because clozapine treatment requires mandated
in patients with headache disorders or chronic gas- monitoring for development of agranulocytosis,
trointestinal disorders. many clinicians now prefer quetiapine for the man-
The mechanisms for the various DIMDs are com- agement of hallucinations and psychosis in patients
plex and not fully understood; however, the term EPS with parkinsonism.10 Dose-related EPS is observed
infers that the pathophysiology of DIMDs is localized with olanzapine and risperidone. Olanzapine at
within subcortical brain regions (eg, basal ganglia 7.5 mg/d is associated with significantly greater EPSs
and thalamus) and does not involve the corticospinal than lower doses and risperidone at 6 to 8 mg/d is
pyramidal motor system. associated with significantly greater EPSs than lower
Traditional consensus has been that a blockade of doses.11 Of the atypical antipsychotics, risperidone
approximately 65% of mesolimbic dopamine recep- appears to be associated with the greatest risk of
tors and 80% of nigrostriatal dopamine receptors is DIMDs, especially at doses greater than 6 mg/d or if
required to elicit antipsychotic and EPSs.5 A positron used concurrently with a cytochrome P450 2D6 or
emission topography study of conventional antipsy- 3A4 inhibitor. The risk of each atypical antipsychotic
chotics by Farde and Nyberg6 found that a dopamine for inducing EPS can be seen in Table 6.

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 DRUG-INDUCED MOVEMENT DISORDERS

Table 2 Table 4
Agents Commonly Implicated in Drug-Induced Agents Commonly Implicated in Drug-Induced
Acute and Tardive Akathisia Acute and Tardive Dystonia

Antiemetics Antiemetics
Droperidol Droperidol
Metoclopramide Metoclopramide
Prochlorperazine
Prochlorperazine
Promethazine
Promethazine Psychotropics
Antiepileptics Amoxapine
Carbamazepine Neuroleptics
Psychotropics Haloperidol
Lithium Phenothiazines
Neuroleptics Thioxanthenes
Haloperidol
Phenothiazines
Thioxanthenes
Reserpine Table 5
Selective serotonin-reuptake inhibitors Agents Commonly Implicated in Drug-Induced Parkinsonism
Tricyclic antidepressants
Antiemetics
Droperidol
Metoclopramide
Prochlorperazine
Table 3
Promethazine
Agents Commonly Implicated in Drug-Induced
Antiepileptics
Tardive Dyskinesia
Valproate
Cardiovascular agents
Antiemetics
α-Methyldopa
Metoclopramide Reserpine
Prochlorperazine Psychotropics
Psychotropics Amoxapine
Neuroleptics Neuroleptics
Haloperidol Haloperidol
Phenothiazines Phenothiazines
Thioxanthenes Thioxanthenes
Vestibular sedatives
Cinnarizinea
Flunarizinea
Miscellaneous
Pimozide
Receptor dissociation may also be important, and Tetrabenazinea
the hypothesis of rapid dissociation from dopamine
a. Not marketed in the United States.
receptors has been proposed to explain the differen-
tial risk between conventional and atypical antipsy-
chotics for inducing EPSs.12,13 The rapid dissociation
from dopamine D2 receptors has been correlated
with low EPS potential. According to this hypothe- would explain the relative risks of EPS induction
sis, atypical antipsychotics bind loosely to dopamine within the class of atypical antipsychotics.
D2 receptors, resulting in a short duration of binding The atypical antipsychotics also block serotonin-2A
that is sufficient to produce antipsychotic activity (5HT-2A) receptors. Serotonin is believed to inhibit
but not long enough to induce EPS. Conventional synaptic dopamine release, and therefore, blockade of
neuroleptics bind tightly to dopamine D2 receptors 5HT-2A receptors has been hypothesized to enhance
and thus produce antipsychotic activity but at an dopamine release to a degree sufficient enough to mit-
increased risk of inducing EPSs. Furthermore, within igate EPS risk without compromising efficacy. For
the antipsychotic class, rapid dissociation occurs each atypical antipsychotic, the ratio of 5HT-2A occu-
more readily with a low-potency agent as opposed to pancy to D2 receptor occupancy in the basal ganglia
a high-potency agent. For example, EPS is rare with may predict the frequency of EPS.7 The significance of
clozapine (an agent that requires higher milligram this mechanism as explanation for reduced EPS asso-
doses for efficacy) as compared with risperidone (an ciated with atypical antipsychotics warrants further
agent that requires lower milligram doses). This study.

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 CLAXTON ET AL

Movement disorders are also associated with other should undergo regular evaluations for DIMDs.
psychotropic medications, such as lithium, selective Atypical antipsychotics are clearly associated with a
serotonin reuptake inhibitors (SSRIs), stimulants, and reduced risk of DIMDs when compared with high-
tricyclic antidepressants. Tremor commonly occurs potency neuroleptics (eg, haloperidol) with or without
with lithium treatment and occasionally chorea.14 SSRIs concurrent antimuscarinic prophylaxis21-25; however,
can commonly cause tremor and less commonly dyski- when compared with low-potency neuroleptics (eg,
nesia, dystonia, or parkinsonism.15 Stimulant drugs (eg, chlorpromazine), the reduced risk of DIMDs associ-
amphetamine, methylphenidate, and pemoline) have ated with the atypical antipsychotics, with the excep-
been known to produce a variety of movement disor- tion of clozapine, appears to be less robust. Early
ders such as dyskinesias, dystonia, stereotypic behav- detection is a key factor in the probability of eventual
ior, and tics.16 The most common movement disorders remission of movement disorders, and if treatment
associated with tricyclic antidepressants are myoclonus with a DRBA has been extended for 3 months or
and tremor.17 The antiepileptic drug valproate is com- longer, the patient should be periodically examined to
monly associated with tremor. For many years, chorea determine the presence of early signs of abnormal
has been recognized as a complication of estrogen- and movements or postures. Although not universal, some
progesterone-containing products.18 Psychotherapeutic clinicians use vitamin E for prophylaxis of TDk and
combination products containing a neuroleptic, such as antimuscarinic agents for prophylaxis of dystonia in
perphenazine/amitriptyline, should not be overlooked high-risk patients.
as causative agents.
AKATHISIA: ACUTE AND TARDIVE
PREVALENCE
The word “akathisia” is a Greek derivative of “not to
The vast majority of DIMDs are associated with neu- sit.” Neuroleptic-induced acute and tardive akathisia is
roleptics. Neuroleptic-induced EPS, akathisia, dysto- a common and distressing adverse effect that is associ-
nia, and parkinsonism occur in a significant number of ated with poor treatment adherence and ultimately
patients who are treated with conventional neurolep- with an increased risk of psychiatric relapse. Drugs
tics. In one study of chronic institutionalized patients commonly associated with akathisia are listed in
with schizophrenia, conventional neuroleptics induced Table 2. Conventional neuroleptics and phenothiazine
movement disorders in 61.6% of patients.19 Of the antiemetics are most commonly implicated in acute
patients with neuroleptic-induced movement disor- akathisia. Atypical antipsychotics may also induce
ders, 31.3% had akathisia, 23.2% had parkinsonism, akathisia, albeit at a much lower rate when compared
and 32.3% had TDk; however, with the advent of the with conventional neuroleptics. The SSRIs are also
atypical antipsychotics, rates of neuroleptic-induced commonly implicated in acute akathisia but rarely in
movement disorders have declined. tardive akathisia. The majority of tardive akathisia
In one study of 125 patients with DRBA-induced cases involve neuroleptics.
movement disorders seen in a movement disorders
clinic, 63% had TDk, 30% had parkinsonism, 24% Epidemiology
had dystonia, and 7% had akathisia.20 Haloperidol
was implicated in 37% of cases, followed by the Reported rates of akathisia vary but are consistently
combination amitriptyline with perphenazine in reported between 20% and 30% for acute akathisia
30%, thioridazine in 27%, chlorpromazine in 20%, and approximately 30% for tardive akathisia.26 The
and metoclopramide in 8%. atypical antipsychotics are associated with lower
In general, older females are more susceptible to rates of akathisia with reported values approximately
developing TDk, young males are more susceptible to 2 to 3 times less than that of conventional neuroleptics.
dystonic reactions, and older persons are more prone In 1 study, the point prevalences of akathisia associ-
to drug-induced parkinsonism (DIP). ated with clozapine, risperidone, and conventional
neuroleptics were 7.3%, 13%, and 23.8%, respec-
THERAPEUTIC MANAGEMENT tively.27 At doses greater than 6 mg/d, risperidone-
induced akathisia increases significantly.
Primary prevention is crucial to the management Although SSRI-induced akathisia has not been
of DIMDs. The necessity of acute or chronic use of systematically studied, it appears to occur in at least
DRBAs should be carefully evaluated. If indicated, the 4.5% of exposed patients.28 Treatment emergent
lowest effective dose should be used, and patients anxiety, agitation, and restlessness are commonly

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Table 6
Association of Medication, Target Dose, and Likelihood of Treatment-Emergent Extrapyramidal Syndromea

Clozapine Haloperidol Olanzapine Quetiapine Risperidone Ziprasidone

Low therapeutic dose – ++ – – + –

High therapeutic dose – +++ ± – ++ ±
Above therapeutic dose – +++ + to ++ – +++ + to ++

Note. – = very unlikely; ± = unlikely; + = occasional; ++ = common; +++ = very common.

a. Aripiprazole is not included here because of limited comparative data and clinical experience on its extrapyramidal syndrome-dose relationship;
however, fixed-dose clinical trials to date have not found a dose-extrapyramidal syndrome relationship for aripiprazole. Adapted from Weiden.7

associated with SSRIs, and it is possible that a sub- akathisia). Occasionally, the withdrawal of a concur-
set of these patients are experiencing akathisia. rent antiakathisia agent (eg, antimuscarinic agent,
Additional investigation is warranted. β blocker) may unmask akathisia. Although the tem-
poral criteria for tardive akathisia are debatable, the
Pathophysiology onset of symptoms after 3 months on a stable drug
treatment is typically considered as tardive. Tardive
The pathophysiologic mechanism of drug-induced akathisia can also occur several months after drug
akathisia is not well understood but may involve a withdrawal or dose reduction. Concurrent symp-
dopamine/serotonin imbalance within cortical and toms of dystonia, parkinsonism, TDk, or tremor are
subcortical areas, with relative excess of serotonergic not uncommon.
activity. This model is supported by the observation Drug-induced akathisia is often clinically indis-
that akathisia is a well-recognized effect of central- tinguishable from syndromes of restlessness caused
acting DRBAs and serotonergic agents such as SSRIs. by medical conditions (eg, iron deficiency, parkin-
Additionally, subcortical norepinephrine pathways sonism, restless legs syndrome), from agitation and
may be involved. anxiety presenting as part of a psychiatric disorder,
and from drug withdrawal syndromes. Acute drug-
Clinical Features induced akathisia should be suspected if symptoms
developed soon after initiation of implicated drugs
Neuroleptic-induced akathisia is comprised of both and in the absence of other conditions associated
a subjective and an objective component. The core with restlessness. In contrast to restless legs syn-
features are subjective complaints of restlessness drome, patients with akathisia report improvement
(commonly of the legs) and at least 1 of the following when lying down or sleeping, an absence of lower
objective findings: fidgety movements or leg swinging extremity paresthesias, an absence of diurnal pat-
while seated, marching on the spot while standing or tern, and an absence of periodic leg movements in
rocking from one foot to another, pacing to relieve sub- sleep. Tardive akathisia may be suspected in the
jective restlessness, or an inability to sit or stand still absence of other conditions associated with restless-
for several minutes.29 The mental unease includes an ness. The symptoms of tardive akathisia are similar
inner sense of restlessness, resulting in anxiety and the to that of acute akathisia, except that tardive patients
urge to move. Significant mental distress is experi- tend to report less distressing subjective symptoms
enced if the patient is asked not to move or if and are able to suppress movements or remain still
restrained from moving. Unlike most movement dis- for longer periods of time.
orders that are involuntary, the movements associated
with akathisia are voluntary and in response to the Risk Factors
subjective feeling of restlessness or discomfort.
Worsening of anxiety and aggressive behavior may Risk factors for akathisia are not well delineated
result in an increase in neuroleptic dose that in turn and are listed in Table 7.26,27,30
may exacerbate the underlying akathisia. Although
tardive akathisia may slowly remit on drug discontin- Morbidity and Mortality
uation, it often remains persistent.
Symptoms of acute akathisia typically occur When left untreated, the symptoms of acute
within 4 weeks of initiating or increasing the dose of akathisia may gradually subside or wax and wane over
the offending drug and may also develop after neu- time. In some patients, acute akathisia may become
roleptic cessation or dose reduction (ie, withdrawal chronic and persist for months or years. Acute

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 CLAXTON ET AL

Table 7 however, these latter agents should be used with cau-

Risk Factors for Drug-Induced Akathisia tion in the cognitively impaired older persons. Less
Advanced age commonly used agents are listed in Table 8.
Affective disorder The treatment of tardive akathisia is difficult, as
Cognitive impairment no pharmacologic intervention consistently pro-
Female
High-potency neuroleptics vides benefit. Management strategies are similar to
High neuroleptic dose that for acute akathisia. Antimuscarinic agents, β-
History of akathisia blockers, and benzodiazepines may be considered,
Iron deficiency
Mental retardation
but improvement may be equivocal.
Negative symptoms of schizophrenia
Rapid neuroleptic dose escalation TDk

TDk is a persistent DIMD that develops after at

least a 1-month exposure to DRBAs. Common drugs
that are associated with TDk are listed in Table 3.
akathisia has been associated with promoting aggres- The term emphasizes the delayed or tardive onset of
sion, psychopathology, suicidal behavior, and treat- choreoathetoid, stereotypic movements, or dyskine-
ment nonadherence in patients with schizophrenia.31 sias secondary to neuroleptic use. Since it was first
reported in the United States in 1960, TDk has
Therapeutic Management become the most recognized movement disorder
induced by neuroleptic treatment.38 Although symp-
Prevention is a key component of treatment. toms may initially be mild, many patients develop
Standardized titration to avoid excessive dose esca- progressively severe TDk, resulting in meaningful
lation and the use of atypical antipsychotics are suc- disability.
cessful measures of prevention. Although iron
deficiency has been associated with acute and tar- Epidemiology
dive akathisia, routine iron supplementation as a
preventive or treatment intervention is not sup- In a study of antipsychotic-naïve patients with
ported by the available evidence.32 It is reasonable to first-episode schizophrenia, the incidence of persis-
correct underlying iron deficiencies or to administer tent TDk increased with longer duration of treat-
oral iron supplementation in akathisia unresponsive ment.39 The cumulative incidence of TDk was 4.8%
to standard measures. In a patient at high risk for after 1 year, 7.2% after 2 years, and 15.6% after
akathisia, concurrent administration of an antimus- 4 years. The antipsychotic drug dose was associated
carinic agent or β-blocker is reasonable. with a modestly increased risk of TDk, with each 100-
The management of akathisia is summarized in mg chlorpromazine equivalent unit increase associ-
Table 8. In the patient experiencing acute akathisia, ated with a 5% increase in TDk risk. It is important to
the causative agent should be discontinued, if possi- note that peculiar choreiform orofacial movements
ble. A switch to an atypical antipsychotic or alternate were observed in schizophrenic patients before the
agent should be considered. In cases of drug discon- advent of conventional neuroleptics and that dyski-
tinuation, the akathisia may promptly resolve, only to nesias may be an intrinsic motor feature of schizo-
be replaced with increased agitation and anxiety. Care phrenia.40 Although spontaneous dyskinesias occur,
should be taken to differentiate this from persistent the former data that demonstrate an increasing inci-
akathisia. Administration of a lipophilic β-blocker, dence of TDk during neuroleptic drug exposure pro-
such as propranolol, is effective and well tolerated.33 vide strong evidence that neuroleptics are clearly
β2 receptor blockade appears to be crucial for efficacy associated with dyskinesias.
as β1 receptor selective agents are less effective34; how- Overall, approximately 20% to 30% of patients
ever, a trial of a cardioselective, β1 receptor blocker is treated with conventional neuroleptics will develop
recommended if a nonselective β-blocker is con- TDk.41,42 Based on studies in young patients, esti-
traindicated or is not tolerated. The hydrophilic β- mates of incidence suggest that TDk develops in
blockers (eg, atenolol and nadolol) do not appear to be approximately 5% of patients with each year of neu-
effective. Administration of antimuscarinic agents (eg, roleptic exposure.43 The geropsychiatric population
benztropine, diphenhydramine), benzodiazepines, or appears to have the highest incidence and preva-
antiserotonergic agents (cyproheptadine) are also lence of TDk, with both conventional and atypical
effective and may be preferred if sedation is desired35-37; agents. In a study of older psychiatric patients who

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Table 8
Management of Drug-Induced Movement Disorders

Acute and tardive akathisia Withdrawal or dosage reduction of offending agent.

If caused by neuroleptic, switch to an atypical antipsychotic.
Trial of antimuscarinic agent or β-blocker.
Miscellaneous antidotes (amantadine, amitriptyline, benzodiazepine, clonidine,
cyproheptadine, mianserin, mirtazapine, codeine, and propoxyphene).
Tardive dyskinesia Withdrawal or dose reduction of offending agent.
Withdrawal of concurrent antimuscarinic agents.
If caused by neuroleptic, switch to an atypical antipsychotic.
Management of concurrent anxiety.
Botulinum toxin (focal dyskinesias).
Trial of amantadine, benzodiazepine, levetiracetam, pregabalin, or vitamin E.
Trial of dopamine-depleting agents (eg, reserpine, tetrabenazine).
Deep brain stimulation (subthalamic nucleus, globus pallidus).
Acute Dystonia Discontinue offending agent.
Administer antimuscarinic agent.
Tardive Dystonia Withdrawal or dose reduction of offending agent.
If caused by neuroleptic, switch to an atypical antipsychotic.
Management of concurrent anxiety.
Botulinum toxin (focal dystonias).
Trial of antimuscarinic agent, benzodiazepine, levetiracetam, or pregabalin.
Trial of muscle relaxant (eg, baclofen).
Trial of dopamine-depleting agents (eg, reserpine, tetrabenazine).
Deep brain stimulation (globus pallidus) or pallidotomy.
Parkinsonism Withdrawal or dose reduction of offending agent.
If caused by neuroleptic, switch to an atypical antipsychotic.
Trial of antimuscarinic, amantadine, dopamine agonist, or levodopa.

had never received neuroleptic agents, 35.4% devel- Pathophysiology

oped TDk after neuroleptic treatment.44 In a prospec-
tive study of previously neuroleptic-naïve patients The pathophysiologic basis of TDk remains specu-
aged 55 years or older, the cumulative incidence of lative, but various neurochemical hypotheses have
TDk was 25%, 34%, and 53% after 1, 2, and 3 years, been proposed, including striatal dopaminergic hyper-
respectively, of cumulative antipsychotic treat- sensitivity, cholinergic deficiency within the basal
ment.45 Older patients appear to be at a least 5 times ganglia, dysfunctions of striatonigral γ-aminobutyric
more at risk for developing TDk as compared with acid (GABA)-mediated neurons, glutamate-induced
young patients.46 excitotoxicity, and oxidative stress.47 Support for some
Neuroleptic-induced TDk is a class effect among of these hypotheses is derived from the observations
the conventional neuroleptics. Although debatable, that antimuscarinic agents enhance TDk, whereas
the risk appears to be similar for all agents within the agents with GABAergic, antiglutaminergic, and
class regardless of formulation. The use of atypical antioxidant activity suppress TDk. Other mechanistic
antipsychotics, regardless of prior neuroleptic expo- factors include attenuation of nitric oxide-mediated
sure, is associated with a reduced risk of TDk.21 In neuromodulation in the striatum, genetic polymor-
one review of 11 studies, atypical antipsychotics phisms of dopamine and serotonin receptor genes,
were associated with a mean annual incidence of and neuroleptic-induced neuronal apoptosis. Ex vivo
new-onset TDk of 0.8% in the adults as compared data from animal models of TDk implicate that presy-
with 5.4% in adults treated with haloperidol.21 These naptic areas such as the substantia nigra are involved.48
data suggest that the risk of TDk associated with The most popular mechanistic hypothesis for TDk
atypical antipsychotics is at least one-fifth that of involves hypersensitization of postsynaptic dopamine
conventional neuroleptics. Despite the fact that most receptors within the basal ganglia (eg, striatum). A
patients had been exposed to conventional neurolep- postmortem study in neuroleptic-treated schizo-
tics before treatment with an atypical antipsychotic, phrenic patients was unable to detect significant
development of TDk was lower as compared with changes in striatal dopamine D1 or D2 receptors
haloperidol-treated patients. In general, if patients do between patients with and without TDk49; however, a
not develop TDk during the initial 5 years of treat- recent in vivo study using radioligand positron emis-
ment, the risk of developing TDk during later years is sion tomography demonstrated that patients with the
reduced. highest degree of dopamine D2 receptor upregulation

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developed severe TDk.50 Within the striatum, GABA The diagnosis of TDk is straightforward in most
and glutamate are the major neurotransmitters that cases. For assessment purposes, the Abnormal
modulate the motor circuit. Evidence suggests that Involuntary Movement Scale (AIMS), developed by
GABA deficiency enhances dyskinesia and that excess the National Institute of Mental Health, is a commonly
glutamate is implicated in neuronal toxicity. Given employed instrument, particularly in the psychiatric
that several hypotheses are plausible, the pathophysi- field.53 The AIMS rates dyskinetic movements in
ology of TDk most likely involves multiple mecha- 7 body regions and includes assessments for global
nisms and events. A unifying hypothesis can be severity, functional impairment, and self-awareness of
proposed whereby the use of DRBAs results in symptoms. Assessment tools, such as the AIMS, may
increased dopamine turnover followed by excess free be used every 3 months to reassess specific symptoms
radical production and subsequent damage to striatal of TDk. Orofacial features include involuntary blink-
GABAergic fibers and reduced inhibitory activity ing, chewing and lower jaw movements, grimacing,
on motor circuits. Concurrently, chronic blockade of lip puckering and smacking, tongue protrusion and
dopamine receptors results in excessive glutamate twisting, and facial tic-like movements. Many patients
activity and resultant excitotoxicity. Likewise, chronic also experience concurrent choreoathetoid or stereo-
dopamine receptor blockade results in receptor super- typic movements of the foot, hands, limbs, trunk,
sensitivity and persistent changes within the basal head, and neck. Movements of the fingers may appear
ganglia motor circuit. as though the patient is playing an invisible guitar or
piano. Occasionally, patients exhibit pelvic rocking
Clinical Features or “copulatory dyskinesia” and grunting or moaning
because of respiratory and pharyngeal dyskinesia.
Symptoms of TDk are characterized by a combina- Factors associated with exacerbation of TDk symp-
tion of involuntary choreiform (rapid, jerky, and non- toms include administration of antimuscarinics or
repetitive), athetoid (slow, sinuous, and writhing), sympathomimetic stimulants and emotional extremes.
and stereotypic (rhythmic and repetitive) move- Symptoms of TDk can be suppressed for brief periods
ments. Regions of the mouth and face (ie, oro-bucco- of time, and distraction during voluntary movements
linguo-masticatory) are most commonly affected, of unaffected body parts (eg, finger tapping test) or
followed by upper and lower limbs. Frequently, TDk during performance of mental tasks (eg, arithmetic)
may occur in the presence of other movement disor- will unmask latent dyskinesia in other body parts.
ders such as akathisia, dystonia, or parkinsonism. As with most dyskinesias, symptoms subside during
The onset of TDk is insidious, and symptoms are ini- sleep, and in mild cases, patients may be unaware of
tially mild and often unnoticeable to patients. the movements.
The vast majority of TDk cases are associated with
antipsychotic treatment. Patients receiving long-term Risk Factors
metoclopramide or phenothiazine antiemetic treat-
ment are also at risk for TDk. Rarely, dyskinesias may Risk factors for the development of TDk are listed
occur with other agents such as antiepileptics, lithium, in Table 9 and include advanced age, affective symp-
oral contraceptives, and SSRIs. If the offending drug is tomatology, alcoholism, total daily drug dosage, dia-
continued, remission of TDk is rare. Occasionally, TDk betes mellitus, duration of treatment, previous
may occur also after withdrawal of chronic DRBA treat- electroconvulsive treatment, female gender, history of
ment. This is reported most commonly in children.51 In EPS, intermittent neuroleptic treatment, iron defi-
general, withdrawal emergent dyskinesia improves ciency, mental retardation, and organic brain disor-
within 3 months. Also, latent TDk may be “unmasked” der.41,42 Age is a well-established risk factor. Not only
after a reduction in neuroleptic dose or during a switch is TDk more common in older persons, but TDk tends
to an atypical antipsychotic. to be more severe and irreversible in this age group. If
When assessing a patient presenting with TDk multiple risk factors are present, an additive effect on
symptoms, the clinician should keep in mind that risk potential is observed; for example, older females
orofacial dyskinesias may also occur in patients with are very susceptible to TDk.
levodopa-induced dyskinesias, Huntington’s disease,
Sydenham’s chorea, hyperthyroidism, and Wilson’s Morbidity and Mortality
disease. Additionally, orofacial dyskinesias may
occur in edentulous individuals and, uncommonly, After TDk develops, remission rates are low if the
in schizophrenic DRBA-naïve patients.52 antipsychotic is continued. In one study, only 11%

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 DRUG-INDUCED MOVEMENT DISORDERS

of patients improved over the course of 5 years.54 If adjunctive vitamin E or benzodiazepines. Anxiety
treatment is discontinued on early detection, remis- often exacerbates TDk and should be treated appro-
sion rates are favorable, especially in the younger priately. Withdrawal of DRBAs may result in notice-
population, but may require several months to years able improvement or remission, particularly if TDk
to resolve. Mild cases are often associated with is recognized early; however, discontinuation of
social impairment such as employment difficulties, antipsychotics for the purpose of treating TDk is a
social isolation, and stigma. In more severe cases, risky option because of the likelihood of psychotic
functional impairment occurs. Patients experience decompensation. The most consistent predictor of
difficulties with chewing, speaking, and swallow- improvement after neuroleptic withdrawal is age
ing. Orofacial dyskinesias may also result in dental with an inverse correlation between rates of remis-
problems, denture displacement, and damage to the sion and age.58 Patients with severe TDk and older
soft tissues within the oral cavity. Gait abnormality persons are less likely to experience remission.
associated with lower-extremity dyskinesia can Occasionally, withdrawal of the DRBA will result
result in falls and injury. in emergence of dyskinesia, particularly if the DRBA
is withdrawn abruptly. Withdrawal dyskinesias are
Therapeutic Management generally self-limiting within 3 months. Generally,
reintroduction of the offending agent with a slow
A summary of the management of TDk is pro- taper will alleviate the dyskinesias.
vided in Table 8. In a recent meta-analyses of evi- In patients on stable neuroleptic maintenance
dence from randomized, controlled trials, more than treatment, a modification to a low or intermittent
500 trials evaluating over 90 different interventions dose regimen may occasionally provide relief but is
were identified.55 The analysis did not yield any associated with relapse risk and may also exacerbate
definitive information on how to best treat TDk. TDk. Switching to an atypical antipsychotic often
Given the lack of good evidence, emphasis is placed results in significant improvement and is the most
on primary prevention, prompt recognition, and appropriate approach if maintenance antipsychotic
management of early and potentially reversible treatment is indicated for an underlying psychiatric
causes. It is reasonable for clinicians to consider the disorder. Increasing the antipsychotic dosage may
use of atypical antipsychotics for long-term therapy suppress the dyskinesias but with the advent of
over that of the older neuroleptics as a means to pre- atypical antipsychotics is considered inappropriate.
vent or reduce the risk for TDk. Other strategies For mild cases, benzodiazepines may be helpful and
include the use of lowest effective DRBA dose and also reduce concomitant anxiety. Vitamin E 1600
eliminating unnecessary, prolonged drug exposure. IU/d may be more beneficial in patients with TDk
Although the use of intermittent antipsychotic treat- for less than 5 years.60 Dopamine-depleting drugs
ment (or drug holidays) may seem like a logical such as reserpine and tetrabenazine are also effec-
strategy for reducing TDk risk, it is actually associ- tive. In young patients, tetrabenazine tends to
ated with an increased risk of TDk and also higher induce depression, whereas older patients tend to
rates of psychosis relapse and rehospitalization.56 experience parkinsonism. The use of reserpine for
The American Psychiatric Association has pub- TDk is limited by development of depression and
lished specific indications for short- and long-term dose-related hypotension. Less commonly used
antipsychotic drug treatment.57 Early detection of agents include acetylcholinesterase inhibitors,
TDk is imperative, as remission rates are inversely amantadine, baclofen, branched chain amino acids,
correlated with duration and severity of TDk. For calcium channel blockers, gabapentin, levetirac-
dyskinesias induced by non-DRBAs (eg, antiepilep- etam, melatonin, methyldopa, and pyridoxine. For
tics, lithium, oral contraceptives, and SSRIs), the patients with severe and refractory TDk, neurosurgi-
movements generally reverse on discontinuation of cal treatments may be effective.61
the offending drug. For neuroleptic-induced TDk,
the movements may improve in up to 50% of DYSTONIA: ACUTE AND TARDIVE
patients after withdrawal of the offending agent, but
overall, complete and long-lasting resolution of TDk Epidemiology
is uncommon.58
Treatment for TDk varies and includes drug dis- The prevalence of drug-induced acute dystonia
continuation, switching to or initiating an atypical (DIAD) has varied widely from 2% to 94% of patients
antipsychotic,59 discontinuing anticholinergics exposed to conventional neuroleptics.62,63 Drugs that
(except in tardive dystonia [TDt]), and initiating are associated with dystonia are listed in Table 4. The

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frequency of DIAD is more commonly associated a diagnosis of neuroleptic malignant syndrome should
with butyrophenone antipsychotics (eg, haloperidol) be considered. Dystonia may also resemble catatonia
as compared with phenothiazine antipsychotics because of underlying psychiatric disorder; however,
(eg, chlorpromazine).64 in contrast to catatonic patients, the patients who
TDt, defined as an involuntary movement pre- develop dystonia will report anxiety and discomfort
dominated by dystonia and associated with the use and seek treatment. Because of the discomfort asso-
of a DRBA, is distinct from TDk, although both often ciated with DIAD, patients are at higher risk for med-
coexist in the same patient.65 TDt occurs in approxi- ication nonadherence and exacerbation of their
mately 2% to 4% of patients exposed to conventional underlying condition.
neuroleptics66,67; however, the actual prevalence may TDt develops after months to years of treatment
be much greater. In one study of inpatient veterans with a DRBA or within 3 months after treatment dis-
on chronic neuroleptic treatment, the prevalence of continuation and often coexists with TDk. Although
TDt was 21.6%.68 DRBAs are most commonly implicated in TDt, drugs
such as SSRIs have been infrequently implicated.69
Pathophysiology Generally, the diagnosis of TDt can be made in the
presence of chronic dystonia (persistent for more
The mechanism of acute and TDts is unclear. than 1 month), clear history of DRBA use, and
Dopaminergic hypofunction within the basal ganglia absence of a general medical or neurologic condition
with subsequent overactivity of the cholinergic that may account for dystonia. In contrast to DIAD,
system has been proposed and is supported by the symptoms of TDt develop insidiously over weeks to
antidystonia activity of antimuscarinic agents. A con- months. Symptoms may or may not be painful and
trasting hypothesis implicates striatal dopaminergic can be isolated to 1 body part or may spread to con-
hyperactivity. Other neurotransmitter systems such as tiguous body parts (segmental dystonia) or even gen-
GABA and serotonin may also contribute. eralize to multiple body parts. Patients often report
that anxiety and stress transiently exacerbate symp-
Clinical Features toms which results in daily variations of symptoma-
tology. The clinical presentation of TDt resembles
The onset of DIAD is sudden, and most cases occur that of an idiopathic focal, segmental, or generalized
within hours to several days of initial exposure to dystonia. In cervical dystonia, the neck muscles con-
DRBAs or less commonly after a DRBA dose increase tract involuntarily and sustained contractions cause
or a reduction in concomitant antimuscarinic agent. abnormal head and neck posturing, whereas peri-
The occurrence of DIAD appears to be greater in odic muscular spasms cause jerky head movements.
younger patients and in patients receiving parenteral The severity of the abnormal posturing may vary
DRBAs. Symptoms include sustained muscular con- from mild to severe; pain may or may not be present,
tractions or spasms that result in abnormal fixed and a dystonic head tremor may be present.
postures or positions of the jaw, neck, shoulders, Blepharospasm affects both eyelids and should not be
trunk, and extremities. The severity of symptoms mistaken for hemifacial spasm, a peripheral nerve
and anatomic distribution varies, but the classic clin- disorder, which is generally unilateral and involves
ical presentation is characterized by the 3 O’s: oculo- twitching or myoclonic spasms affecting the eyelids,
gyric crisis (conjugate deviation of the eyes upward or cheeks, and mouth regions. Tardive oromandibular
laterally), opisthotonos (involuntary posturing in dystonia is associated with persistent difficulty in
which the head, neck, and spine are arched back- opening or closing the mouth and affects chewing,
ward), and oromandibular dystonia (forceful contrac- speech, and swallowing. Bruxist activity may also
tions of the jaw, causing difficulty in opening or accompany jaw closing dystonia. Spasms in the
closing the mouth). Blepharospasm (involuntary eye- tongue also interfere with eating and swallowing.
lid closure), trismus (jaw-closing dystonia), laryngeal Pisa syndrome is a rare form of dystonia that is
spasm, tongue protrusion, and respiratory stridor may most commonly associated with neuroleptic treat-
also be present. Symptoms are usually painful and ment and characterized by sustained truncal lat-
can interfere with ambulation, breathing, speaking, eroflexion.70 Drug-induced Pisa syndrome is more
swallowing, and vision. In severe cases, DIAD may be common in patients who are older and female, who
life threatening. Rhabdomyolysis caused by sustained are receiving combination antipsychotics, or who
muscle contraction may also occur. If dystonia occurs have organic brain pathology (eg, dementia). The
in the presence of fever, generalized rigidity, an altered onset of Pisa syndrome may be acute or tardive.
level of consciousness, and autonomic instability, Treatment consists of administering antimuscarinic

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 DRUG-INDUCED MOVEMENT DISORDERS

Table 9 Table 10
Risk Factors for Tardive Dyskinesias Risk Factors of Dystonia

Advanced age Acute Dystonia

Affective disorder High-potency neuroleptics
Alcoholism History of electroconvulsive therapy
Diabetes mellitus Male
Duration of treatment Mental retardation
Electroconvulsive treatment Young age
Female Tardive Dystonia
History of extrapyramidal reaction Male
Intermittent neuroleptic treatment Presence of tardive dyskinesia
Iron deficiency Young age
Mental retardation
Organic brain disorder
Total daily drug dose
Morbidity and Mortality

Acute dystonia resolves when the offending drug

is discontinued or the dose is reduced. In severe
agents and withdrawing or reducing daily doses of cases (eg, laryngeal spasm), DIAD may be life threat-
the causative agent. As with TDt, Pisa syndrome ening, and severe generalized dystonia may result in
responds more favorably than TDk to antimuscarinic rhabdomyolysis and associated complications. The
treatment; however, unlike TDt, symptoms of Pisa acute dystonia may be painful and distressing to the
syndrome generally abate after withdrawal of the patient and result in medication nonadherence.
causative agent. Thus, Pisa syndrome may be con- Rarely, patients with TDt may experience “status
sidered as an atypical subtype of TDt. dystonicus,” a life-threatening condition associated
In addition to idiopathic dystonia, other condi- with severe dystonic spasms resulting in rhabdomy-
tions such as Huntington’s disease, Wilson’s disease, olysis, myoglobinuria, and renal failure. In the case
levodopa-responsive dystonia, or conversion reac- of TDt, remission is uncommon.
tion must be excluded. In addition, other conditions
that cause a twisted neck such as orthopedic or con- Therapeutic Management
genital problems of the neck, ophthalmologic condi-
tions resulting in head tilt to compensate for double The management of acute and TDts is summarized
vision, stiff neck, arthritis, or wry neck. in Table 8. Several studies comparing the incidence of
neuroleptic-induced acute dystonia with and without
Risk Factors the concomitant use of antimuscarinic agents (eg,
benztropine, diphenhydramine, trihexyphenidyl)
Risk factors for the development of acute dystonia report that the administration of concurrent antimus-
include young age, a history of electroconvulsive carinic agents reduces the overall rate of dystonia by
therapy, male gender, mental retardation, and the at least twofold.64,72,73 In patients treated with high-
use of high-potency neuroleptics (Table 10).71 As potency neuroleptics, the reduction is even greater
with other DIMDs, the presence of multiple risk fac- at 5- to 11-fold.72,74 Because the greatest risk of
tors has an additive effect on risk. An inverse rela- neuroleptic-induced acute dystonia occurs within the
tionship exists between the incidence of DIAD and first week of drug treatment, the short-term administra-
age. In contrast to TDk, dystonia is uncommon in tion of oral antimuscarinic agents may be considered,
older patients. The highest risk population is young especially in young patients receiving high-potency
males on high potency neuroleptics. antipsychotics.
Risk factors for TDt overlap with some of the risk The efficacy of antimuscarinic prophylaxis appears
factors for DIAD and include young age, male sex, to be inversely related to the age of the patient.
and the presence of TDk (Table 10). Children are at Because of the reduced prophylactic efficacy and
particularly greater risk of TDt as compared with undesirable antimuscarinic adverse reactions, the use
adults. The duration of exposure is not consistently of antimuscarinic agents in older patients for primary
correlated with risk of TDt. TDt may develop after a prevention of DIAD is disfavored. Currently, the prac-
short exposure or after years of treatment. In some tice of antimuscarinic primary prophylaxis is contro-
cases, TDt may develop subsequent to a dose versial but appears to be reasonable in patients at high
increase despite a long, stable period of treatment. risk of developing dystonia.

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 CLAXTON ET AL

Acute dystonia can be effectively relieved with a Pathophysiology

short course of a potent antimuscarinic agent (eg, ben-
ztropine, diphenhydramine) administered orally, The risk of DRBA-induced parkinsonism appears
intramuscularly, or intravenously. If life-threatening to be directly correlated to occupancy at striatal
dystonia is present, intravenous administration is dopamine receptors and inversely correlated with
warranted, and supportive measures such as tra- striatal to frontal dopamine receptor occupancy.79
cheostomy may be required. Benzodiazepines may Relative to the conventional neuroleptics, the atypi-
be administered if the administration of an antimus- cal antipsychotic agents possess lower affinities for
carinic agent is contraindicated. striatal dopaminergic receptors and more rapid
Aside from local injections of botulinum toxin for receptor dissociation. This has been associated with
focal dystonias, few treatments have proven to be con- a reduced risk of DIP. In addition the DRBAs, drugs
sistently useful for the treatment of TDt; therefore, that deplete presynaptic dopamine (eg, reserpine,
emphasis is placed on primary prevention. The tetrabenazine) or act as dopamine “false transmit-
chronic use of conventional DRBAs (eg, neuroleptics ters” (eg, α-methyldopa) may also induce parkinson-
and metoclopramide) should be carefully evaluated ism. Valproate is an underrecognized source of DIP
and alternatives considered. If the causative agent can- due to insidious onset of parkinsonian symptoms.80
not be discontinued, a concomitant antimuscarinic The underlying mechanism is unknown but may be
agent may be administered for symptomatic treatment. due to increased γ-aminobutyric acid (GABA) activ-
Atypical antipsychotics, benzodiazepines, muscle ity within the striatum or thalamus. The SSRIs are
relaxants, and dopamine-depleting drugs, such as uncommonly associated with DIP, although SSRI
tetrabenazine, are also effective and may be used in induced tremor is common.
combination with antimuscarinics. The response to
systemic pharmacologic agents varies among patients, Clinical Features
and combination therapy may be required. Less com-
monly used drugs include amantadine, β-blockers, In general, the clinical features are indistinguish-
benzodiazepines, clonidine, dantrolene, levodopa, able from idiopathic parkinsonism and include at
and antiepileptics such as levetiracetam, pregabalin, least 2 of the following: tremor (rest or postural),
tiagabine, and zonisamide. For focal dystonic symp- rigidity, and bradykinesia. In the absence of an accu-
toms, local injections of botulinum toxin are preferred rate drug history, symptoms of DIP can be easily mis-
because of the relative lack of systemic adverse effects taken for idiopathic parkinsonism. Recognition of
and consistent efficacy among patients. In refractory DIP may be difficult as symptoms such as reduced
and severe cases, intrathecal baclofen and deep brain facial expression, reduced energy and motivation,
stimulation of the globus pallidus or ablative pallido- and bradykinesia can mimic negative symptoms of
tomy may be effective.75,76 schizophrenia as well as psychomotor retardation
associated with depressive disorders. The presence
PARKINSONISM of tremor without bradykinesia or rigidity is not
parkinsonism. Classic DIP is characterized by sym-
Epidemiology metrical distribution of symptoms and a low-
frequency, high-amplitude jaw tremor. In the majority
DIP is considered the second most common form of cases, DIP is a subacute process that develops
of parkinsonism. In one study of older patients, 51% within 3 months of initiating the offending agent or,
of newly referred parkinsonism cases were attribut- in some cases, after a dose increase and is reversible
able to drugs.77 Drugs that may induce or exacerbate on drug withdrawal. Occasionally, the onset may be
parkinsonism are listed in Table 5. Of all drugs, the acute.
DRBAs are most commonly implicated and world-
wide are responsible for 70% to 80% of DIP. The Risk Factors
prevalence of parkinsonism associated with conven-
tional neuroleptics ranges from 20% to 66%.19,78 The Risk factors for the development of DIP are listed
prevalence of parkinsonism associated with atypical in Table 11 and include patients who are EPS vul-
antipsychotics is much lower. In one study, the nerable (eg, advanced age, dementia, or preexisting
prevalence of parkinsonian rigidity associated with parkinsonism), female, and use central DRBAs.
clozapine, risperidone, and conventional neurolep- Patients with acquired immune deficiency syndrome
tics was 4.9%, 17.4%, and 35.7%, respectively.27 (AIDS) appear to be very susceptible to developing

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 DRUG-INDUCED MOVEMENT DISORDERS

Table 11 DIMDs can be categorized by onset of symptoms: acute

Risks Factors for Drug-Induced Parkinsonism reactions occurring hours to days after exposure, sub-
Acquired immune deficiency syndrome acute DIMDs appearing within weeks, and tardive
Advanced age occurring months to years after drug exposure. For
Dementia many of these disorders, treatment inconsistently pro-
Female
vides benefit, and therefore, primary prevention is
essential. Knowledge of DIMDs should allow health-
care professionals to better identify patients with
DIMDs, or those at risk, and implement prevention
DIP. In one study, the likelihood of developing EPS and treatment plans.
was 2.4 times higher among patients with AIDS as
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