What is the maximum dose of Thorazine (chlorpromazine)?

Maximum Dose of Thorazine (Chlorpromazine)

The maximum dose of chlorpromazine is 2,000 mg per day, though doses exceeding 1,000 mg per day rarely provide additional therapeutic benefit for extended periods. 1

FDA-Approved Dosing Guidelines

The FDA label provides clear guidance on maximum dosing based on clinical setting 1:

Hospitalized Patients with Acute Psychosis

• Initial treatment: Start with injectable chlorpromazine until the patient is controlled (typically 24-48 hours)
• Oral transition: 500 mg/day is generally sufficient once the patient becomes quiet and cooperative
• Maximum dose: While gradual increases to 2,000 mg/day or more may be necessary, there is usually little therapeutic gain achieved by exceeding 1,000 mg/day for extended periods 1
• Special populations: Lower doses should be used in elderly, emaciated, and debilitated patients 1

Outpatients and Less Severe Cases

• Standard dosing: 400 mg/day is the usual effective dose 1
• Discharged mental patients: 800 mg/day is not uncommon 1

Evidence-Based Dosing Considerations

Therapeutic Threshold for Treatment-Resistant Schizophrenia

• A minimum dose equivalent to 600 mg/day is considered therapeutic for treatment-resistant schizophrenia 2
• Treatment trials should last at least 4-6 weeks at adequate doses before determining efficacy 2

Dose-Response Relationship

Low-quality evidence from comparative trials suggests 3:

• Low dose: ≤ 400 mg/day
• Medium dose: 401-800 mg/day
• High dose: > 800 mg/day

When comparing low-dose (≤400 mg/day) to high-dose (>800 mg/day) chlorpromazine, the high-dose group showed significantly more people improving globally, but also experienced markedly more extrapyramidal symptoms (RR 0.43,95% CI 0.32 to 0.59) and had more people leaving studies early due to adverse effects 3

Critical Safety Considerations

Cardiovascular Risk

Chlorpromazine carries significant cardiovascular risks, particularly at higher doses 4:

• Associated with QTc prolongation and increased risk of ventricular arrhythmias
• Adjusted odds ratio of 1.45 (95% CI 0.93 to 2.27) for ventricular arrhythmia/sudden cardiac death 4
• Orthostatic hypotension is common, especially in elderly and debilitated patients 4

Extrapyramidal Symptoms

Higher doses (>800 mg/day) are associated with significantly more extrapyramidal adverse effects compared to lower doses 3, 5

Practical Dosing Algorithm

1. Start low: Begin with 25 mg TID or 10 mg QID for outpatients 1
2. Titrate gradually: Increase by 20-50 mg at semi-weekly intervals until symptoms are controlled 1
3. Target range: Aim for 400-800 mg/day for most patients 1, 3
4. Maximum ceiling: Do not exceed 1,000 mg/day for extended periods unless absolutely necessary 1
5. Absolute maximum: 2,000 mg/day should be considered the upper limit 1
6. Maintenance: After 2 weeks at optimum dosage, gradually reduce to the lowest effective maintenance level 1

When to Consider Alternative Treatment

If no response occurs after 4-6 weeks at therapeutic doses (≥600 mg/day), switch to a different antipsychotic rather than continuing to escalate chlorpromazine 2