Introduction
Chlorpromazine is a first-generation (typical) phenothiazine antipsychotic medication that revolutionized psychiatric treatment following its introduction in the 1950s. It was the first drug specifically developed for psychiatric use and remains an important agent in clinical practice today. Chlorpromazine is primarily used for the management of psychotic disorders but also possesses significant antiemetic, antihistaminic, and anticholinergic properties.
Mechanism of Action
Chlorpromazine exerts its therapeutic effects primarily through antagonism of dopamine D2 receptors in the mesolimbic pathway of the brain. It also blocks:
- Alpha-1 adrenergic receptors (causing orthostatic hypotension)
- Histamine H1 receptors (causing sedation)
- Muscarinic cholinergic receptors (causing anticholinergic effects)
- Serotonin 5-HT2 receptors
The drug's antipsychotic effects are primarily attributed to its dopamine receptor blockade in the central nervous system, particularly in areas associated with psychosis and emotional regulation.
Indications
FDA-Approved Indications:- Treatment of schizophrenia
- Management of manic phase of bipolar disorder
- Severe behavioral problems in children
- Control of nausea and vomiting
- Preoperative apprehension and anxiety
- Acute intermittent porphyria
- Adjunct in treatment of tetanus
- Treatment of psychotic depression
- Management of agitation in dementia (with caution)
- Intractable hiccups
- Migraine headache prophylaxis
Dosage and Administration
Oral Administration:- Adults: Initial dose 10-25 mg PO 2-4 times daily, gradually increased to 200-800 mg/day in divided doses
- Elderly: Lower initial doses (10-25 mg 1-2 times daily) with gradual titration
- Children (>6 months): 0.25 mg/kg PO every 4-6 hours as needed
- IM: 25-50 mg initially, may repeat in 1 hour if needed
- IV: 25-50 mg diluted and administered slowly (reserved for severe cases)
- Hepatic impairment: Reduce dose by 30-50%
- Renal impairment: Use with caution; consider dose reduction
- Geriatric patients: Start with lowest possible dose
Pharmacokinetics
Absorption: Well absorbed from GI tract but undergoes significant first-pass metabolism (bioavailability 20-80%) Distribution: Widely distributed throughout body tissues; crosses blood-brain barrier and placenta Protein Binding: 90-95% bound to plasma proteins Metabolism: Extensive hepatic metabolism via cytochrome P450 system (primarily CYP2D6) Elimination: Half-life 16-30 hours; excreted in urine (as metabolites) and feces Time to Peak Effect: 2-4 hours orally; 15-30 minutes IMContraindications
- Hypersensitivity to chlorpromazine or other phenothiazines
- Comatose states or CNS depression from alcohol, barbiturates, or opioids
- Bone marrow suppression
- Severe cardiovascular disease
- Narrow-angle glaucoma
- Prostatic hypertrophy with urinary retention
Warnings and Precautions
Black Box Warning: Increased mortality in elderly patients with dementia-related psychosis- Extrapyramidal symptoms: Risk of tardive dyskinesia (may be irreversible)
- Neuroleptic malignant syndrome: Potentially fatal reaction requiring immediate discontinuation
- QT prolongation: May cause torsades de pointes
- Seizures: Lowers seizure threshold
- Agranulocytosis: Monitor blood counts regularly
- Hepatotoxicity: Periodic liver function tests recommended
- Orthostatic hypotension: Particularly with initial dosing
- Temperature dysregulation: Impaired thermoregulation
Drug Interactions
Major Interactions:- CNS depressants (alcohol, benzodiazepines, opioids): Enhanced sedation
- Anticholinergic agents: Increased anticholinergic effects
- Antihypertensives: Potentiated hypotension
- Levodopa: Decreased effectiveness
- QT-prolonging agents: Increased risk of cardiac arrhythmias
- CYP2D6 inhibitors (fluoxetine, paroxetine): Increased chlorpromazine levels
Adverse Effects
Common (≥10%):- Sedation/drowsiness
- Orthostatic hypotension
- Dry mouth
- Blurred vision
- Constipation
- Weight gain
- Tardive dyskinesia
- Neuroleptic malignant syndrome
- Agranulocytosis
- Seizures
- Jaundice
- Severe extrapyramidal symptoms
- Cardiac arrhythmias
Monitoring Parameters
- Baseline: CBC with differential, liver function tests, ECG, renal function
- Ongoing:
- Mental status and therapeutic response - Extrapyramidal symptoms assessment (AIMS scale) - Vital signs (especially blood pressure) - Weight and BMI - Periodic CBC and LFTs - ECG monitoring in high-risk patients
- Therapeutic Drug Monitoring: Not routinely required
Patient Education
- Take medication as prescribed; do not stop abruptly
- Avoid alcohol and other CNS depressants
- Rise slowly from sitting/lying position to prevent dizziness
- May cause drowsiness - use caution when driving or operating machinery
- Report any unusual movements, fever, muscle rigidity, or sore throat immediately
- Use sun protection as medication may increase photosensitivity
- Maintain adequate hydration
- Notify all healthcare providers of chlorpromazine use
- Use reliable contraception as medication may affect fetal development
References
1. American Psychiatric Association. (2020). Practice Guideline for the Treatment of Patients With Schizophrenia. 2. Lehne, R. A., et al. (2020). Pharmacology for Nursing Care. 10th edition. 3. Lexicomp Online. (2023). Chlorpromazine: Drug Information. 4. Stahl, S. M. (2021). Stahl's Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 5th edition. 5. FDA Prescribing Information: Chlorpromazine Hydrochloride Tablets. 6. Miller, D. D., & Caroff, S. N. (2020). Contemporary Use of First-Generation Antipsychotics. CNS Drugs, 34(5), 501-513. 7. Marder, S. R., & Cannon, T. D. (2019). Schizophrenia. New England Journal of Medicine, 381(18), 1753-1761.
This monograph is for educational purposes only. Always consult appropriate prescribing information and clinical guidelines before initiating therapy.