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Am J Psychiatry. 1997 Sep;154(9):1243-7.

Time to clozapine response in a standardized trial.

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  • 1Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, USA.



The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia.


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.


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).


In this study, all patients who responded to clozapine did so within 8 weeks of a change in dose. Thus, there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen.

[PubMed - indexed for MEDLINE]
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