Time to clozapine response in a standardized trial

Objective: The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia. Method: Antipsychotic response to a clozapine trial was examined in 50 treatment- refractory schizophrenic inpatients. Subjects were treated with clozapine for at least 12 months, regardless of response status, according to a standardized, increasing dose protocol. Behavioral changes were measured through monthly assessments with the Brief Psychiatric Rating Scale. Results: Thirty-four subjects (68%) met clinical response criteria by the end of the trial. Response was achieved at a mean dose of 468 mg/day (SD= 168). The dose of 30 (88%) of the responding patients was 600 mg/day or less. The mean time to response was 82 days (SD=100, range= 10-401). It took an average of 60 days (SD=87) for subjects to reach the dose at which clozapine response was achieved. Once this dose was reached, the average response time was 17 days (SD= 14, range=2-56). All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation. No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks (SD=50). Conclusions: In this study, all patients who responded to clozapine did so within 8 weeks of a change in dose. Thus, there appears to he little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen.