Chlorpromazine (Thorazine)

Class

First-generation (typical) antipsychotic; phenothiazine derivative

Mechanism

Dopamine D2 receptor antagonist; also blocks histamine, cholinergic, and alpha-adrenergic receptors

FDA-Approved Use

Schizophrenia, psychotic disorders, severe behavioral problems in children, nausea/vomiting, intractable hiccups

Off-Label Use

Agitation and aggression in neurodevelopmental disabilities (higher adverse risk)

Formulation

Oral tablets, intramuscular injection, suppository

Titration

25–50 mg p.o. BID, titrated gradually

Dose Range

100–800 mg/day

Kinetics

Hepatic metabolism; half-life ~30 hours

Common AEs

Sedation, orthostatic hypotension, anticholinergic effects, weight gain

Serious/Rare AEs

Tardive dyskinesia, neuroleptic malignant syndrome, cholestatic jaundice, prolonged QT interval

Monitoring

Monitor for EPS (e.g., AIMS every 6–12 months), weight and metabolic parameters periodically, and ECG if cardiac risk factors or polypharmacy. Consider prolactin or liver enzymes if symptomatic.

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis

Considerations

Chlorpromazine carries higher risk of sedation, hypotension, and EPS in neurodevelopmental disabilities; reserve for severe cases when other agents fail. Use with caution in elderly and those with cardiovascular disease.