PMID: 8942454Dec 1, 1996Paper

Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges

The American Journal of Psychiatry
C VanderZwaagT Cooper

Abstract

This study sought to determine the relationships between serum clozapine levels and therapeutic response. Fifty-six inpatients who met the DSM-III-R criteria for chronic schizophrenia and who had not responded to extended treatment with classical antipsychotics were randomly assigned to 12 weeks of double-blind treatment with clozapine at one of three serum level ranges: low (50-150 ng/ml), medium (200-300 ng/ml), or high (350-450 ng/ml). Baseline clinical assessments were completed before the patients' regular antipsychotic and anticholinergic drugs were discontinued. During clozapine treatment, serum levels were ascertained weekly to allow adjustment of clozapine doses so as to maintain each patient near the midpoint of his or her assigned serum level range. Clinical assessments were completed after 6 and 12 weeks of treatment. The analyses of the results of treatment supported the superior efficacy of the 200-300 ng/ml and 350-450 ng/ml serum clozapine level ranges over the 50-150 ng/ml range, with no advantage for 350-450 ng/ml over 200-300 ng/ml. Sleepiness increased with increasing serum levels. Serum clozapine levels per unit of daily dose were at the lower end of the range noted in previous reports, possibly reflecting ...Continue Reading

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