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Am J Psychiatry 1991; 148:231-235
Copyright © 1991 by American Psychiatric Association
Clozapine and norclozapine plasma concentrations and clinical response of treatment-refractory schizophrenic patients [published erratum appears in Am J Psychiatry 1991 Oct;148(10):1427]
PJ Perry, DD Miller, SV Arndt and RJ Cadoret
Department of Psychiatry, College of Medicine, University of Iowa, Iowa City.
OBJECTIVE: Clozapine, an atypical antipsychotic, has been estimated to be
effective in 30% of treatment-refractory schizophrenic patients. The
authors hypothesized that if a dose-response relationship was obvious for
this drug, the response rate could be significantly amplified. METHOD:
Following an 8-24-day dose titration phase, 29 inpatients with
treatment-resistant schizophrenia diagnosed according to DSM-III-R were
given a clozapine dose of approximately 400 mg/day for 4 weeks; blood
samples were obtained weekly during this period. RESULTS: A receiver
operator curve demonstrated that the threshold clozapine plasma
concentration for therapeutic response was 350 ng/ml. Sixty-four percent of
the patients with clozapine plasma concentrations greater than 350 ng/ml
responded, whereas only 22% of the patients with concentrations less than
350 ng/ml responded. CONCLUSIONS: Use of clozapine blood levels as a
predictor for treatment response in treatment-refractory schizophrenic
patients appears worthwhile, since the measurement's sensitivity for
response was 64% and the specificity for nonresponse was 78%.
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