What is the dosage and usage of Chlorpromazine (chlorpromazine) for treating schizophrenia and other psychoses?

Chlorpromazine Dosage and Usage for Schizophrenia and Psychoses

Initial Dosing Strategy

For acute schizophrenia or manic states in hospitalized patients, start with 25 mg three times daily and increase gradually by 20-50 mg at semi-weekly intervals until symptoms are controlled, typically reaching 400-500 mg daily, though doses up to 1,000 mg daily may be needed in some cases. 1

Hospitalized Patients with Acute Symptoms

• Acute schizophrenic or manic states: Begin with 25 mg three times daily, then increase every few days until the patient becomes calm and cooperative 1
• Most patients respond adequately to 500 mg daily, though gradual increases to 2,000 mg daily may be necessary in severe cases 1
• There is usually little therapeutic gain beyond 1,000 mg daily for extended periods 1
• For prompt control of severe symptoms, intramuscular administration may be used initially, followed by oral doses of 25-50 mg three times daily 1

Outpatients and Less Acutely Disturbed Patients

• Outpatients: Start with 10 mg three to four times daily, or 25 mg two to three times daily 1
• Less acutely disturbed hospitalized patients: Begin with 25 mg three times daily and increase gradually until effective dose is reached, usually 400 mg daily 1
• More severe outpatient cases: Start with 25 mg three times daily, then increase by 20-50 mg at semi-weekly intervals 1

Therapeutic Dose Requirements

A minimum dose equivalent to 600 mg/day of chlorpromazine is considered therapeutic for treatment-resistant schizophrenia. 2

• Daily dosages of 200 mg are not unusual in standard practice 1
• Some patients, particularly discharged mental patients, may require higher dosages (e.g., 800 mg daily is not uncommon) 1
• The evidence shows no clear superiority of medium doses (401-800 mg/day) over low doses (≤400 mg/day) for global and mental state outcomes 3
• However, high doses (>800 mg/day) showed better global state improvement compared to low doses, though at the cost of significantly more extrapyramidal symptoms 3

Treatment Duration and Response Assessment

Antipsychotic therapy must be implemented for at least 4-6 weeks using adequate dosages before efficacy can be determined. 2

• Continue optimum dosage for 2 weeks after maximum improvement is achieved 1
• Maximum improvement may not be seen for weeks or even months 1
• Additional improvement may occur over 6-12 months following the acute presentation, so medication should be maintained during this period 2
• Early response at 48 hours can predict eventual treatment outcome 4

Maintenance and Dose Reduction

After symptoms are controlled for a reasonable period, gradually reduce dosage to the lowest effective maintenance level. 1

• Gradual dose reduction may be indicated to decrease side effects, including negative symptoms, while carefully monitoring for relapse 2
• Monthly physician contact is recommended to adequately monitor symptom course, side effects, and compliance 2

Treatment-Resistant Cases

If no results are apparent after 4-6 weeks at adequate doses, or if side effects are unmanageable, trial a different antipsychotic. 2

• If a patient fails to respond to two adequate trials of different antipsychotics (at least 4 weeks each at therapeutic doses), clozapine should be considered 2
• Clozapine is the only antipsychotic with sufficient research documenting its superiority in efficacy for treatment-resistant cases 2
• For clozapine, aim for plasma levels of at least 350 ng/mL, with doses potentially increased to achieve concentrations up to 550 ng/mL if response is inadequate 2, 5

Special Populations

Elderly and Debilitated Patients

Dosages in the lower range are sufficient for most elderly patients, as they are more susceptible to hypotension and neuromuscular reactions. 1

• Increase dosage more gradually in elderly and debilitated patients 1
• In general, dosage levels should be lower in the elderly, emaciated, and debilitated 1
• Orthostatic hypotension is particularly common in elderly patients 2

Pediatric Patients (6 months to 12 years)

• Chlorpromazine should generally not be used in children under 6 months except where potentially lifesaving 1
• Oral dosing: ¼ mg/lb body weight every 4-6 hours as needed (e.g., 10 mg every 4-6 hours for a 40 lb child) 1
• In severe behavior disorders, higher dosages (50-100 mg daily, and in older children up to 200 mg daily or more) may be necessary 1
• There is little evidence that doses beyond 500 mg per day further enhance behavior improvement in severely disturbed mentally retarded patients 1
• Depot formulations are not recommended for children with very early-onset schizophrenia 2

Cardiovascular and Safety Considerations

Chlorpromazine carries significant cardiovascular risks, particularly QTc prolongation and increased risk of ventricular arrhythmias, with an adjusted odds ratio of 1.45 for ventricular arrhythmia/sudden cardiac death. 2

• Orthostatic hypotension is common, especially in elderly and debilitated patients 2
• Hypotension occurs more frequently with chlorpromazine compared to haloperidol (NNH 7) 6
• Observe patients closely for hypotension and neuromuscular reactions 1

Adverse Effects Profile

Movement Disorders

• Chlorpromazine causes fewer extrapyramidal symptoms compared to haloperidol 6
• However, medium doses (401-800 mg/day) cause significantly more extrapyramidal symptoms than low doses (≤400 mg/day) 3
• High doses (>800 mg/day) substantially increase the risk of extrapyramidal symptoms compared to low doses 3

Other Common Side Effects

• Sedation: Chlorpromazine is clearly sedating (NNH 6) 7
• Weight gain: Considerable increases in weight occur (NNH 3) 7
• Seizures: Risk may increase with chlorpromazine, though data are limited 7

Efficacy Evidence

Chlorpromazine reduces relapse over 6 months to 2 years (NNT 3) and promotes global improvement in symptoms and functioning (NNT 7). 7

• The placebo response is also considerable, but chlorpromazine demonstrates clear superiority 7
• Fewer people allocated to chlorpromazine leave trials early, though this difference is not always statistically significant 7
• Chlorpromazine's global position as a 'benchmark' treatment for psychoses remains unchallenged by current evidence 7