CHLORPROMAZINE

THERAPEUTICS If It Works
• Most often reduces positive symptoms in
Brands • Thorazine
schizophrenia but does not eliminate them
see index for additional brand names
• Most schizophrenic patients do not have a
Generic? Yes total remission of symptoms but rather a
reduction of symptoms by about a third
• Continue treatment in schizophrenia until
Class reaching a plateau of improvement
• Neuroscience-based Nomenclature: • After reaching a satisfactory plateau,
dopamine and serotonin receptor continue treatment for at least a year after
antagonist (DS-RAn) first episode of psychosis in schizophrenia
• Conventional antipsychotic (neuroleptic, • For second and subsequent episodes of
phenothiazine, dopamine 2 antagonist, psychosis in schizophrenia, treatment may
antiemetic) need to be indefinite
• Reduces symptoms of acute psychotic
Commonly Prescribed for mania but not proven as a mood stabilizer
(bold for FDA approved) or as an effective maintenance treatment in
• Schizophrenia bipolar disorder
• Nausea, vomiting • After reducing acute psychotic symptoms
• Restlessness and apprehension before in mania, switch to a mood stabilizer and/
surgery or an atypical antipsychotic for mood
• Acute intermittent porphyria stabilization and maintenance
• Manifestations of manic type of manic-
depressive illness
If It Doesn’t Work
• Tetanus (adjunct) • Consider trying one of the first-line atypical
• Intractable hiccups antipsychotics (risperidone, olanzapine,
• Combativeness and/or explosive quetiapine, ziprasidone, aripiprazole,
hyperexcitable behavior (in children) paliperidone, amisulpride, asenapine,
• Hyperactive children who show excessive iloperidone, lurasidone)
motor activity with accompanying conduct • Consider trying another conventional
disorders consisting of some or all of antipsychotic
the following symptoms: impulsivity, • If 2 or more antipsychotic monotherapies
difficulty sustaining attention, do not work, consider clozapine
aggressivity, mood lability, and poor Best Augmenting Combos
frustration tolerance for Partial Response or
• Psychosis Treatment Resistance
• Bipolar disorder
• Augmentation of conventional antipsychotics
has not been systematically studied
• Addition of a mood-stabilizing anticonvulsant
How the Drug Works such as valproate, carbamazepine,
• Blocks dopamine 2 receptors, reducing or lamotrigine may be helpful in both
positive symptoms of psychosis and schizophrenia and bipolar mania
improving other behaviors • Augmentation with lithium in bipolar mania
• Combination of dopamine D2, histamine may be helpful
H1, and cholinergic M1 blockade in the • Addition of a benzodiazepine, especially
vomiting center may reduce nausea and short-term for agitation
vomiting
Tests
How Long Until It Works ✽ Since conventional antipsychotics are
• Psychotic symptoms can improve within frequently associated with weight gain,
1 week, but it may take several weeks for before starting treatment, weigh all patients
full effect on behavior and determine if the patient is already
• Actions on nausea and vomiting are overweight (BMI 25.0–29.9) or obese
immediate (BMI ≥30)

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• Before giving a drug that can cause • Antihistaminic actions may cause sedation,
weight gain to an overweight or obese weight gain
patient, consider determining whether the • By blocking alpha 1 adrenergic receptors,
patient already has pre-diabetes (fasting it can cause dizziness, sedation, and
plasma glucose 100–125 mg/dL), diabetes hypotension
(fasting plasma glucose >126 mg/dL), or • Mechanism of weight gain and any
dyslipidemia (increased total cholesterol, possible increased incidence of diabetes
LDL cholesterol and triglycerides; or dyslipidemia with conventional
decreased HDL cholesterol), and treat or antipsychotics is unknown
refer such patients for treatment, including
nutrition and weight management, physical Notable Side Effects
activity counseling, smoking cessation, and ✽ Neuroleptic-induced deficit syndrome
medical management ✽ Akathisia
✽ Monitor weight and BMI during treatment ✽ Priapism
✽ Consider monitoring fasting triglycerides ✽ Extrapyramidal symptoms, parkinsonism,
monthly for several months in patients at tardive dyskinesia
high risk for metabolic complications and ✽ Galactorrhea, amenorrhea
when initiating or switching antipsychotics • Dizziness, sedation, impaired memory
✽ While giving a drug to a patient who • Dry mouth, constipation, urinary retention,
has gained >5% of initial weight, consider blurred vision
evaluating for the presence of pre-diabetes, • Decreased sweating
diabetes, or dyslipidemia, or consider • Sexual dysfunction
switching to a different antipsychotic • Hypotension, tachycardia, syncope
• Should check blood pressure in the elderly • Weight gain
before starting and for the first few weeks
of treatment
Life-Threatening or
• Monitoring elevated prolactin levels of
dubious clinical benefit
Dangerous Side Effects
• Phenothiazines may cause false positive • Rare neuroleptic malignant syndrome
phenylketonuria results • Rare jaundice, agranulocytosis
• Patients with low white blood cell count • Rare seizures
(WBC) or history of drug-induced • Increased risk of death and cerebrovascular
leucopenia/neutropenia should have events in elderly patients with dementia-
complete blood count (CBC) monitored related psychosis
frequently during the first few months and Weight Gain
chlorpromazine should be discontinued
at the first sign of decline of WBC in the
absence of other causative factors
• Many experience and/or can be significant
in amount
SIDE EFFECTS
Sedation
How Drug Causes Side Effects
• By blocking dopamine 2 receptors in the
striatum, it can cause motor side effects • Tolerance to sedation can develop over
• By blocking dopamine 2 receptors in the time
pituitary, it can cause elevations in prolactin
• By blocking dopamine 2 receptors What to Do About Side Effects
excessively in the mesocortical and • Wait
mesolimbic dopamine pathways, especially • Wait
at high doses, it can cause worsening • Wait
of negative and cognitive symptoms • For motor symptoms, add an
(neuroleptic-induced deficit syndrome) anticholinergic agent
• Anticholinergic actions may cause sedation, • Reduce the dose
blurred vision, constipation, dry mouth • For sedation, give at night

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• Switch to an atypical antipsychotic • One of the few antipsychotics available as

• Weight loss, exercise programs, and a suppository
medical management for high BMIs, • Treatment should be suspended if absolute
diabetes dyslipidemia neutrophil count falls below 1,000/mm3

Best Augmenting Agents for Side Overdose

Effects • Extrapyramidal symptoms, sedation,
• Benztropine or trihexyphenidyl for motor hypotension, coma, respiratory depression
side effects
• Sometimes amantadine can be helpful for Long-Term Use
motor side effects • Some side effects may be irreversible (e.g.,
• Benzodiazepines may be helpful for tardive dyskinesia)
akathisia
• Many side effects cannot be improved with Habit Forming
an augmenting agent • No

How to Stop
• Slow down-titration of oral formulation
DOSING AND USE (over 6–8 weeks), especially when
simultaneously beginning a new
Usual Dosage Range antipsychotic while switching (i.e., cross-
• 200–800 mg/day titration)
• Rapid oral discontinuation may lead to
Dosage Forms rebound psychosis and worsening of
• Tablet 10 mg, 25 mg, 50 mg, 100 mg, symptoms
200 mg • If antiparkinson agents are being used,
• Capsule 30 mg, 75 mg, 150 mg they should be continued for a few weeks
• Ampul 25 mg/mL; 1 mL, 2 mL after chlorpromazine is discontinued
• Vial 25 mg/mL; 10 mL
• Liquid 10 mg/5 mL Pharmacokinetics
• Suppository 25 mg, 100 mg • Half-life approximately 8–33 hours
How to Dose
• Psychosis: increase dose until symptoms
are controlled; after 2 weeks reduce to
Drug Interactions
lowest effective dose • May decrease the effects of levodopa,
• Psychosis (intramuscular): varies by dopamine agonists
severity of symptoms and inpatient/ • May increase the effects of antihypertensive
outpatient status drugs except for guanethidine, whose
antihypertensive actions chlorpromazine
may antagonize
• Additive effects may occur if used with
Dosing Tips CNS depressants
• Low doses may have more sedative actions • Some pressor agents (e.g., epinephrine)
than antipsychotic actions may interact with chlorpromazine to lower
• Low doses have been used to provide blood pressure
short-term relief of daytime agitation and • Alcohol and diuretics may increase the risk
anxiety and to enhance sedative hypnotic of hypotension
actions in nonpsychotic patients, but • Reduces effects of anticoagulants
other treatment options such as atypical • May reduce phenytoin metabolism and
antipsychotics are now preferred increase phenytoin levels
• Higher doses may induce or worsen • Plasma levels of chlorpromazine and
negative symptoms of schizophrenia propranolol may increase if used
• Ampuls and vials contain sulfites that may concomitantly
cause allergic reactions, particularly in • Some patients taking a neuroleptic and
patients with asthma lithium have developed an encephalopathic

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syndrome similar to neuroleptic malignant • Elderly patients with dementia-related

syndrome psychosis treated with antipsychotics are
at an increased risk of death compared to
placebo, and also have an increased risk of
Other Warnings/ cerebrovascular events
Precautions
• If signs of neuroleptic malignant syndrome
develop, treatment should be immediately
discontinued Children and Adolescents
• Use cautiously in patients with alcohol • Can be used cautiously in children or
withdrawal or convulsive disorders because adolescents over age 1 with severe
of possible lowering of seizure threshold behavioral problems
• Use with caution in patients with • Oral – 0.25 mg/lb every 4–6 hours as
respiratory disorders, glaucoma, or urinary needed; rectal – 0.5 mg/lb every 6–8 hours
retention as needed; IM – 0.25 mg/lb every 6–8
• Avoid extreme heat exposure hours as needed; maximum 40 mg/day
• Avoid undue exposure to sunlight (under 5), 75 mg/day (5–12)
• Antiemetic effect of chlorpromazine may • Do not use if patient shows signs of Reye’s
mask signs of other disorders or overdose; syndrome
suppression of cough reflex may cause • Generally consider second-line after
asphyxia atypical antipsychotics
• Use only with caution if at all in Parkinson’s
disease or Lewy body dementia

Do Not Use
• If patient is in a comatose state Pregnancy
• If patient is taking metrizamide or large • Effective June 30, 2015, the US FDA
doses of CNS depressants requires changes to the content and format
• If there is a proven allergy to chlorpromazine of pregnancy and lactation information
• If there is a known sensitivity to any in prescription drug labels, including
phenothiazine the elimination of the pregnancy letter
categories; the Pregnancy and Lactation
Labeling Rule (PLLR or final rule) applies
only to prescription drugs and will be
SPECIAL POPULATIONS phased in gradually for drugs approved on
Renal Impairment or after June 30, 2001
• Controlled studies have not been
• Use with caution
conducted in pregnant women
Hepatic Impairment • There is a risk of abnormal muscle
• Use with caution movements and withdrawal symptoms
in newborns whose mothers took an
Cardiac Impairment antipsychotic during the third trimester;
• Cardiovascular toxicity can occur, symptoms may include agitation,
especially orthostatic hypotension abnormally increased or decreased
muscle tone, tremor, sleepiness,
Elderly severe difficulty breathing, and difficulty
• Lower doses should be used and patient feeding
should be monitored closely • Reports of extrapyramidal symptoms,
• Often do not tolerate sedating actions of jaundice, hyperreflexia, hyporeflexia
chlorpromazine in infants whose mothers took a
• Although conventional antipsychotics phenothiazine during pregnancy
are commonly used for behavioral • Chlorpromazine should generally not be
disturbances in dementia, no agent has used during the first trimester
been approved for treatment of elderly • Chlorpromazine should be used during
patients with dementia-related psychosis pregnancy only if clearly needed

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• Psychotic symptoms may worsen during the availability of alternative treatments

pregnancy and some form of treatment make its utilization outside of psychosis a
may be necessary short-term and second-line treatment option
• Atypical antipsychotics may be preferable • Chlorpromazine is a low-potency
to conventional antipsychotics or phenothiazine
anticonvulsant mood stabilizers if treatment • Sedative actions of low-potency
is required during pregnancy phenothiazines are an important aspect of
their therapeutic actions in some patients
Breast Feeding and side effect profile in others
• Some drug is found in mother’s breast • Low-potency phenothiazines like
milk chlorpromazine have a greater risk of
• Effects on infant have been observed cardiovascular side effects
(dystonia, tardive dyskinesia, sedation) • Patients have very similar antipsychotic
✽ Recommended either to discontinue drug responses to any conventional
or bottle feed antipsychotic, which is different from
atypical antipsychotics where antipsychotic
responses of individual patients can
THE ART OF PSYCHOPHARMACOLOGY occasionally vary greatly from one atypical
antipsychotic to another
Potential Advantages • Patients with inadequate responses to
• Intramuscular formulation for emergency atypical antipsychotics may benefit
use from a trial of augmentation with a
• Patients who require sedation for conventional antipsychotic such as
behavioral control chlorpromazine or from switching to
a conventional antipsychotic such as
Potential Disadvantages chlorpromazine
• Patients with tardive dyskinesia • However, long-term polypharmacy
• Children with a combination of a conventional
• Elderly antipsychotic such as chlorpromazine
• Patients who wish to avoid sedation with an atypical antipsychotic may
combine their side effects without clearly
Primary Target Symptoms augmenting the efficacy of either
• Positive symptoms of psychosis • For treatment-resistant patients,
• Motor and autonomic hyperactivity especially those with impulsivity,
• Violent or aggressive behavior aggression, violence, and self-harm,
long-term polypharmacy with 2 atypical
antipsychotics or with 1 atypical
antipsychotic and 1 conventional
Pearls antipsychotic may be useful or even
• Chlorpromazine is one of the earliest necessary while closely monitoring
classical conventional antipsychotics • In such cases, it may be beneficial to
• Chlorpromazine has a broad spectrum of combine 1 depot antipsychotic with 1 oral
efficacy, but risk of tardive dyskinesia and antipsychotic

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Suggested Reading
Adams CE, Awad G, Rathbone J, Thornley people with schizophenia already stable on
B. Chlorpromazine versus placebo for chlorpromazine. Cochrane Database Syst Rev
schizophrenia. Cochrane Database Syst Rev 2007;24(1):CD006329.
2007;18(2):CD000284.
Leucht C, Kitzmantel M, Chua L, Kane J, Leucht
Ahmed U, Jones H, Adams CE. S. Haloperidol versus chlorpromazine for
Chlorpromazine for psychosis induced schizophrenia. Cochrane Database Syst Rev
aggression or agitation. Cochrane Database 2008;23(1):CD004278.
Syst Rev 2010;14(4):CD007445.
Liu X, De Haan S. Chlorpromazine dose for
Almerie MQ, Alkhateeb H, Essali A, Matar people with schizophrenia. Cochrane Database
HE, Rezk E. Cessation of medication for Syst Rev 2009;15(2):CD007778.

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