How to Start Chlorpromazine (Thorazine)
For outpatients with psychotic disorders, start chlorpromazine at 10 mg three times daily or 25 mg two to three times daily, with gradual dose increases every 1-2 days by 20-50 mg at semi-weekly intervals until the patient becomes calm and cooperative. 1
Initial Dosing Strategy by Clinical Setting
Outpatients with Less Acute Psychosis
- Start with 10 mg three times daily (TID) or four times daily (QID), or alternatively 25 mg twice daily (BID) or TID 1
- For more severe outpatient cases, begin with 25 mg TID 1
- After 1-2 days, increase daily dosage by 20-50 mg at semi-weekly intervals until symptoms are controlled 1
Hospitalized Patients with Acute Schizophrenia or Mania
- For acute presentations, initial treatment should be with intramuscular chlorpromazine until the patient is controlled (usually 24-48 hours) 1
- Once cooperative, switch to oral dosing at 25-50 mg TID, gradually increasing until the patient is calm 1
- 500 mg daily is generally sufficient for most hospitalized patients 1
- While doses can be gradually increased to 2,000 mg daily, there is usually little therapeutic gain beyond 1,000 mg daily for extended periods 1
Special Population Considerations
Elderly and Debilitated Patients
- Use lower starting doses and increase more gradually 1
- Elderly patients are more susceptible to hypotension and neuromuscular reactions and require close observation 1
- Dosages in the lower range are sufficient for most elderly patients 1
Pediatric Patients (6 months to 12 years)
- For severe behavioral problems in outpatients: 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
- Start with low doses and increase gradually 1
- In severe behavior disorders, higher dosages (50-100 mg daily, or 200 mg daily in older children) may be necessary 1
Dose Titration and Maintenance
Therapeutic Dosing Targets
- A minimum dose equivalent to 600 mg/day of chlorpromazine is considered therapeutic for treatment-resistant schizophrenia 2
- For most patients, 400 mg daily is typical, though some require higher doses (800 mg daily is not uncommon in discharged mental patients) 1
- Maximum improvement may not be seen for weeks or even months 1
Duration of Therapeutic Trial
- Antipsychotic therapy should be implemented for no less than 4-6 weeks using adequate dosages before efficacy can be determined 2
- 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 2
Critical Safety Considerations
Cardiovascular Monitoring
- Chlorpromazine carries significant cardiovascular risks, particularly QTc prolongation and increased risk of ventricular arrhythmias (adjusted OR 1.45) 2
- Orthostatic hypotension is common, especially in elderly and debilitated patients 2
Extrapyramidal Symptoms
- Higher doses (>400 mg/day) are associated with significantly more extrapyramidal symptoms compared to lower doses 3, 4
- When comparing 401-800 mg/day to ≤400 mg/day, the higher dose group had approximately twice the risk of extrapyramidal symptoms 3
When to Switch or Escalate Treatment
Treatment Failure Criteria
- If no results are apparent after 4-6 weeks, or if side effects are unmanageable, a trial of a different antipsychotic should be undertaken 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 superiority in treatment-resistant cases 2