chlorpromazine

General Information

Chlorpromazine is a low-potency FGA (phenothiazine) used for schizophrenia and other psychotic disorders. It is also labeled for several non-psychiatric indications such as nausea/vomiting and intractable hiccups (label-dependent).

Compared with high-potency FGAs, chlorpromazine is typically less “motor-heavy” (lower EPS burden at comparable antipsychotic effect) but more “body-heavy”: sedation, orthostatic hypotension, and anticholinergic side effects are common practical limitations (label/clinical).

Low-potency phenothiazines can still cause tardive dyskinesia and neuroleptic malignant syndrome, so the risk conversation is not simply about drowsiness; periodic movement-disorder screening remains part of routine use (label/clinical).

The chlorpromazine compare view, evidence feed, and print page support side-by-side trade-off discussions.

Chlorpromazine is an older, inexpensive antipsychotic with broad label indications. In contemporary practice it is often used selectively when sedation/antiemetic goals or prior response are important, but its orthostasis and anticholinergic burden can be function-limiting compared with many newer options (AHRQ/clinical).

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Dopamine D2 receptor antagonism is the primary antipsychotic mechanism.

H1 antagonism contributes to sedation and weight/appetite effects.

Muscarinic antagonism contributes to anticholinergic effects (dry mouth, constipation, urinary retention, delirium risk).

α1 antagonism contributes to orthostatic hypotension and dizziness.

• D2 receptor antagonism (antipsychotic effect).
• H1 antagonism (sedation).
• Antimuscarinic activity (anticholinergic effects).
• α1 antagonism (orthostasis).

Metabolism and Pharmacokinetics

• Chlorpromazine undergoes hepatic metabolism and has variable clinical exposure across patients; titration is generally guided by response and tolerability rather than serum levels (label/clinical).
• Because chlorpromazine is frequently used alongside other sedatives in medically ill patients (e.g., as an antiemetic), total CNS depressant burden is a practical pharmacodynamic consideration (clinical).

Dosing and Administration

• Dosing is individualized by indication and setting. The label emphasizes gradual titration until symptoms are controlled, then step-down to the lowest effective maintenance dose (label).
• Psychotic disorders: label examples include outpatient starts such as 10 mg three or four times daily or 25 mg two or three times daily; more severe cases may be titrated upward in semi-weekly intervals (label).
• Hospitalized acute schizophrenia or mania: the label notes 500 mg/day is generally sufficient, with gradual increases up to 2,000 mg/day sometimes necessary; it suggests limited gain from >1,000 mg/day for extended periods (label).
• Non-psychiatric label examples include nausea/vomiting dosing of 10–25 mg every 4–6 hours as needed and intractable hiccups dosing of 25–50 mg three or four times daily (label).
• Older adults and medically frail patients are typically started at lower doses and titrated more gradually because hypotension and neuromuscular reactions may be more prominent (label/clinical).

Monitoring & Labs

• Sedation and functional impairment (falls risk, driving safety).
• Orthostatic symptoms and blood pressure (especially early titration).
• Anticholinergic effects (bowel/urinary symptoms, delirium risk).
• Movement symptoms (akathisia, rigidity, tremor; tardive dyskinesia screening).
• Weight and cardiometabolic risk factors over time.

Adverse Effects

Interactions

• Additive CNS depression with alcohol, opioids, benzodiazepines, sedating antihistamines, and other sedatives (clinical).
• Additive anticholinergic burden with TCAs, bladder antimuscarinics, and other anticholinergics can increase delirium and urinary retention risk (clinical).
• QT-prolonging combinations and electrolyte abnormalities can increase arrhythmia risk; ECG monitoring is commonly considered when multiple risk factors exist (clinical).

Other Useful Information

• For schizophrenia, modern care pathways often compare oral FGAs vs SGAs and consider LAI options early when adherence is uncertain (APA).
• When chlorpromazine is used for non-psychiatric indications in complex inpatients, documenting the short-term goal and stop plan helps prevent open-ended sedative stacking (clinical).

References

1. Chlorpromazine hydrochloride tablets prescribing information — DailyMed (2025)
2. First Generation Versus Second Generation Antipsychotics IN Adults: Comparative Effectiveness — Agency for Healthcare Research and Quality (NCBI Bookshelf) (2012)
3. The American Psychiatric Association Practice Guideline for the Treatment of Patients With Schizophrenia — American Psychiatric Association (2020)
4. AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology — Pharmacopsychiatry (2018)