Starting Dose of Clozapine in Adults with Schizophrenia
Begin clozapine at 12.5 mg once or twice daily on day 1, then increase by 25-50 mg increments added to the total daily dose no more than once or twice per week. 1
Initial Dosing Strategy
Start with 12.5 mg once or twice daily on the first day to minimize risks of orthostatic hypotension, bradycardia, and syncope 1
Increase the dose by 25-50 mg increments added to the total daily dose, with increases occurring no more than once or twice per week 1
Never increase doses more rapidly than 25-50 mg per week, even in severely ill patients, as rapid dose escalation significantly increases seizure risk, particularly in the first weeks of treatment 1
Special Considerations for Early Psychosis
For patients within their first year of psychosis onset, an even slower titration approach may be warranted, as these patients can achieve sustained response at remarkably low maintenance doses (mean dose of 81 mg/day) 2
Slow titration in early psychosis leads to better tolerability and acceptance of clozapine treatment while maintaining clinical efficacy 2
Target Dosing and Therapeutic Levels
The typical target dose range is 200-400 mg/day, which usually corresponds to therapeutic plasma trough levels of 350-550 ng/mL 1, 3
Measure trough plasma clozapine levels (12 hours post-dose) on at least two occasions separated by one week at a stable dose to ensure therapeutic levels are achieved 1, 4
Target a trough plasma clozapine level of 350-550 ng/mL for optimal efficacy 1
Critical Safety Monitoring During Titration
Obtain weekly WBC and ANC for the first 6 months to monitor for agranulocytosis 1
Monitor closely for orthostatic hypotension, bradycardia, and syncope during the initial titration phase 1
Seizure risk is particularly elevated during rapid titration and at plasma levels >550 ng/mL 1
Common Pitfalls to Avoid
Do not titrate faster than recommended even if the patient appears severely ill, as this dramatically increases seizure risk 1
Do not assume adequate trial without measuring plasma levels—some patients, especially young male smokers, may require doses higher than 900 mg/day to achieve therapeutic levels 5
Smoking status dramatically affects clozapine metabolism through CYP1A2 induction, requiring dose adjustments and close monitoring 1