What is the dosage and usage of Chlorpromazine for a patient with schizophrenia or acute psychosis?

Chlorpromazine Dosing for Schizophrenia and Acute Psychosis

For acute schizophrenia or psychosis, start with 25 mg three times daily and gradually increase to 400-800 mg/day in divided doses, as doses above 600 mg/day show minimal additional benefit while significantly increasing adverse effects. 1, 2

Initial Dosing Strategy

Outpatient Management

• Start with 10 mg three to four times daily, or 25 mg two to three times daily for less acutely disturbed patients 1
• For more severe outpatient cases, begin with 25 mg three times daily, then increase by 20-50 mg at semi-weekly intervals until the patient becomes calm and cooperative 1
• The usual effective dose is 400 mg daily 1

Hospitalized Patients with Acute Psychosis

• For acute schizophrenic or manic states, initial treatment with intramuscular chlorpromazine is recommended until the patient is controlled, typically within 24-48 hours 1
• Once stabilized, switch to oral dosing and increase gradually until the patient is calm 1
• 500 mg daily is generally sufficient, with little therapeutic gain achieved by exceeding 1000 mg daily for extended periods 1
• While gradual increases to 2000 mg daily may be necessary in rare cases, doses of 800 mg daily are not uncommon in discharged mental patients 1

Therapeutic Dose Range and Evidence

Optimal Dosing Window

• A minimum dose equivalent to 600 mg/day of chlorpromazine is considered therapeutic for treatment-resistant schizophrenia 3
• Doses ≤ 400 mg/day (low dose) versus 401-800 mg/day (medium dose) show no clear benefit of higher dosing for global or mental state outcomes 2
• When comparing low dose (≤ 400 mg/day) to high dose (> 800 mg/day), the high-dose group showed more people improving but at the cost of significantly more people leaving the study due to adverse effects 2

Duration of Treatment Trial

• Antipsychotic therapy must be implemented for at least 4-6 weeks using adequate dosages before efficacy can be determined 3
• If no results are apparent after 4-6 weeks, or if side effects are unmanageable, switch to a different antipsychotic 3
• Continue optimum dosage for 2 weeks after maximum improvement, then gradually reduce to the lowest effective maintenance level 1
• Additional improvement may occur over 6-12 months following the acute presentation 3

Dose Titration and Monitoring

Gradual Escalation Protocol

• Increase dosage gradually until symptoms are controlled, with maximum improvement potentially taking weeks to months 1
• Dosage should be increased more gradually in debilitated, emaciated, or elderly patients who are more susceptible to hypotension and neuromuscular reactions 1
• After symptoms are controlled for a reasonable period, gradually reduce dosage to the lowest effective maintenance level 1

Baseline and Ongoing Monitoring Requirements

• Before starting chlorpromazine, obtain baseline measurements including BMI, waist circumference, blood pressure, HbA1c or fasting glucose, lipid panel, prolactin, liver function tests, urea and electrolytes, full blood count, and ECG 3
• Recheck fasting glucose at 4 weeks 3
• Monitor BMI, waist circumference, and blood pressure weekly for 6 weeks 3
• Repeat all baseline measures annually 3

Adverse Effects and Safety Considerations

Cardiovascular Risks

• Chlorpromazine carries significant cardiovascular risks, particularly at higher doses, with QTc prolongation and increased risk of ventricular arrhythmias (adjusted OR 1.45,95% CI 0.93 to 2.27) 3
• Orthostatic hypotension is common, especially in elderly and debilitated patients 3
• Intravenous chlorpromazine should only be used in bed-bound patients due to its hypotensive side effects 4

Extrapyramidal Symptoms

• Medium doses (401-800 mg/day) cause significantly more extrapyramidal symptoms compared to low doses (≤ 400 mg/day) (2 RCTs, n=108, RR 0.47,95% CI 0.30 to 0.74) 2
• High doses (> 800 mg/day) cause markedly more extrapyramidal symptoms in general (RR 0.43,95% CI 0.32 to 0.59) 2
• For akathisia, consider dose reduction, switch to quetiapine or olanzapine, or add propranolol 10-30 mg two to three times daily 3

Other Common Adverse Effects

• Chlorpromazine is clearly sedating (n=1404,19 RCTs, RR 2.63,95% CI 2.1 to 3.3, NNH 5) 5
• Causes considerable weight gain (n=165,5 RCTs, RR 4.92,95% CI 2.3 to 10.4, NNH 2) 5
• Causes lowering of blood pressure with accompanying dizziness (n=1394,16 RCTs, RR 2.37,95% CI 1.7 to 3.2, NNH 11) 5
• Consider prophylactic metformin when starting chlorpromazine, beginning at 500 mg once daily and increasing to 1 g twice daily maximum, after assessing renal function 3

Treatment-Resistant Cases

When to Switch Medications

• If a patient fails to respond after 4-6 weeks at therapeutic doses, undertake a trial of a different antipsychotic 3
• 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 3
• Clozapine is the only antipsychotic with sufficient research documenting its superiority in efficacy for treatment-resistant cases 3

Special Populations

Elderly Patients

• In general, dosages in the lower range are sufficient for most elderly patients 1
• Observe closely as elderly patients are more susceptible to hypotension and neuromuscular reactions 1
• Tailor dosage to the individual, monitor response carefully, and adjust accordingly 1

Pediatric Patients (6 months to 12 years)

• Chlorpromazine should generally not be used in pediatric patients under 6 months of age except where potentially lifesaving 1
• For severe behavioral problems in outpatients: ¼ mg/lb body weight every 4-6 hours as needed (e.g., for a 40 lb child, 10 mg every 4-6 hours) 1
• For hospitalized patients with severe behavior disorders, higher dosages (50-100 mg daily, and in older children 200 mg daily or more) may be necessary 1
• There is little evidence that behavior improvement in severely disturbed mentally retarded patients is further enhanced by doses beyond 500 mg per day 1

Critical Clinical Pitfalls

• Avoid exceeding 1000 mg daily for extended periods, as there is little therapeutic gain and substantially increased adverse effects 1, 2
• Do not use benzodiazepines as initial treatment for delirium in patients not already taking them 4
• Review and minimize anticholinergic burden, as chlorpromazine has high central anticholinergic activity 3
• Monthly physician contact is recommended to adequately monitor symptom course, side effects, and compliance 3