chlorpromazine

Phenothiazine antipsychotic· Brands: Largactil, ThorazineIMIVPO

Mechanism of action

Chlorpromazine is a phenothiazine antipsychotic that blocks dopamine D2 receptors in the central nervous system, particularly in the mesolimbic and mesocortical pathways. It also antagonises alpha-adrenergic, histamine H1, and muscarinic receptors, which accounts for its sedative, hypotensive, and anticholinergic effects.

Pharmacokinetics

Chlorpromazine is well absorbed after oral administration but undergoes extensive first-pass metabolism, resulting in variable bioavailability (approximately 30-50%). It is highly protein bound and widely distributed, including across the blood-brain barrier. Metabolism is predominantly hepatic via CYP2D6 and other isoenzymes, and the elimination half-life is around 30 hours. Excretion is mainly in urine as metabolites, with some in faeces.

Indications & dosing

Schizophrenia and other psychoses

Start at the low end and titrate gradually; higher doses may be used under specialist care.

adult · PO: 25–100 mg 3 times daily · Start at the low end and titrate gradually; higher doses may be used under specialist care.

Acute agitation or psychosis

IV route not recommended; monitor blood pressure and sedation.

adult · IM: 25–50 mg every 2-4h PRN · IV route not recommended; monitor blood pressure and sedation.

Nausea and vomiting

An alternative is intramuscular injection if oral not possible.

adult · PO: 10–25 mg every 4-6 hours · An alternative is intramuscular injection if oral not possible.

Intractable hiccupsoff-label

Stop if no response after 2-3 days.

adult · PO: 25–50 mg 3 times daily · Stop if no response after 2-3 days.

Severe anxiety (short term)

Short-term use only; avoid in elderly with dementia.

adult · PO: 10–25 mg 3 times daily · Short-term use only; avoid in elderly with dementia.

Contraindications & precautions

Hypersensitivity to chlorpromazine or other phenothiazines · Cross-sensitivity may occur among phenothiazines.
Coma or severe central nervous system depression · Including that induced by alcohol, barbiturates, or opioids.
Bone marrow depression or history of blood dyscrasias · Chlorpromazine can further suppress haematopoiesis.
Phaeochromocytoma · Risk of precipitating hypertensive crisis.
Use with caution in epilepsy, as chlorpromazine may lower seizure threshold.
Use with caution in patients with hepatic or renal impairment, as drug accumulation may occur.
Use with caution in cardiovascular disease, including bradycardia and hypokalaemia, due to risk of QT prolongation.
Use with caution in elderly patients with dementia, since antipsychotics increase mortality risk in this population.
Use with caution in Parkinson's disease, as dopamine blockade may worsen symptoms.
Avoid abrupt withdrawal; taper dose gradually to minimize risk of rebound symptoms or withdrawal dyskinesia.

Adverse effects

Sedation
Anticholinergic effects (dry mouth, blurred vision, constipation)
Postural hypotension
Extrapyramidal symptoms (acute dystonia, akathisia, parkinsonism)
Tardive dyskinesiaserious
Neuroleptic malignant syndromeserious
QT interval prolongation and ventricular arrhythmiasserious
Agranulocytosisserious

Renal & hepatic adjustment

eGFR 0–30: Use with caution; plasma levels may be increased in severe renal impairment. No specific dose adjustment usually required, but monitor for adverse effects.
Hepatic impairment (mild): No specific adjustment required, but monitor liver function tests and observe for signs of hepatic toxicity.
Hepatic impairment (moderate): Reduce dose and monitor liver function; consider alternative if hepatic dysfunction worsens.
Hepatic impairment (severe): Avoid; contraindicated in severe hepatic impairment due to risk of accumulation and toxicity. (avoid)

Monitoring, pregnancy & toxicity

Blood pressure · Baseline and periodically during dose titration, especially in elderly
ECG (QT interval) · Before treatment and periodic follow-up in patients with cardiac risk factors or on other QT-prolonging drugs
Liver function tests · Baseline and periodically during treatment
Full blood count · Baseline and monitor for signs of infection, as agranulocytosis can occur
Extrapyramidal symptoms · Regularly assess for parkinsonism, akathisia, and tardive dyskinesia
Pregnancy: Use only if clearly needed and benefits outweigh risks. Avoid during first trimester and near term if possible. Neonatal sedation and withdrawal symptoms have been reported.
Toxicity: CNS depression: drowsiness, coma, respiratory depression · Supportive care; ensure airway and breathing, monitor vital signs, consider activated charcoal if within 1 hour of ingestion.
Toxicity: Hypotension and cardiac arrhythmias (prolonged QT, ventricular arrhythmias) · Fluid resuscitation, vasopressors (e.g., norepinephrine) if needed; avoid adrenaline (epinephrine) as it may cause paradoxical hypotension. Continuous ECG monitoring.
Toxicity: Extrapyramidal symptoms: acute dystonia, oculogyric crisis, parkinsonism · Administer anticholinergic like procyclidine or benztropine.
Toxicity: Anticholinergic and hypothermic effects: dry mouth, hyperthermia or hypothermia, seizures · Supportive measures, temperature management, benzodiazepines for seizures.

Clinical notes

Chlorpromazine is used for schizophrenia, other psychoses, and in the management of mania, agitation, and behavioural disturbances. It is also used for intractable hiccoughs and as an antiemetic. Common adverse effects include sedation, postural hypotension, dry mouth, constipation, and extrapyramidal symptoms (parkinsonism, akathisia, tardive dyskinesia). Neuroleptic malignant syndrome is a rare but serious complication. Use with caution in epilepsy, cardiovascular disease, and in the elderly. Avoid in Parkinson's disease. Dose reduction may be necessary in hepatic insufficiency.

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BNF; local formulary