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Am J Psychiatry 1994; 151:1744-1752
Copyright © 1994 by American Psychiatric Association
Clinical effects of clozapine in chronic schizophrenia: response to treatment and predictors of outcome
JA Lieberman, AZ Safferman, S Pollack, S Szymanski, C Johns, A Howard, M Kronig, P Bookstein and JM Kane
Hillside Hospital, Long Island Jewish Medical Center, Glen Oaks, NY 11004.
OBJECTIVE: This study addressed the unique clinical properties attributed
to the atypical antipsychotic clozapine, including its efficacy in patients
with treatment-refractory psychosis and against negative symptoms, its lack
of acute extrapyramidal side effects, and the longer time course of its
therapeutic effects. METHOD: The clinical responses of 84 schizophrenic
inpatients (66 with treatment-refractory illness and 18 who were intolerant
of antipsychotic treatment) were examined. After all previous antipsychotic
medications had been withdrawn, the patients were treated with clozapine
according to a standardized titration and dosage schedule. Patients who
tolerated and responded to treatment were discharged and maintained on a
regimen of clozapine for up to 52 weeks. Patients were evaluated for
behavioral response and side effects after weeks 3, 6, 12, 26, 39, and 52
of treatment. RESULTS: Fifty percent of the patients with treatment-
refractory illness and 76% of the treatment-intolerant patients responded
to clozapine in up to 52 weeks. The optimal period for a trial of clozapine
appeared to be 12-24 weeks. Clozapine exhibited therapeutic effects on
negative symptoms, but these were not clearly independent of its effects on
positive symptoms and extrapyramidal side effects. Several variables,
including early age at onset of illness and female gender, were found to be
predictors of poor response to treatment. Predictors of good response
included the presence of extrapyramidal side effects during previous
treatment with classic neuroleptics and a diagnosis of paranoid
schizophrenia. CONCLUSIONS: These findings have important implications for
the use of clozapine and our understanding of the pathophysiology of
treatment-resistant schizophrenia.
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