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Clinical and Neurocognitive Effects of Clozapine and Risperidone in Treatment-Refractory Schizophrenic Patients: A Prospective Study

J Clin Psychiatry 1998;59(10):521-527

Background: Few controlled studies have compared the efficacy of clozapine and risperidone in treatment- refractory schizophrenic patients. The present study investigates the efficacy of both clozapine and risperidone on psychopathologic and neurocognitive measures in a prospective 12-week open-label trial in treatment-refractory schizophrenic patients from state psychiatric hospitals.

Method: Thirty-five DSM-IV schizophrenic patients with a documented history of nonresponse to typical neuroleptics were treated with either clozapine or risperidone. Response was assessed every 2 weeks by independent raters with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI) scale, neurologic rating scales, and plasma drug levels. Neurocognitive tests were administered at baseline and week 12.

Results: Both clozapine and risperidone brought about significant (p < .003) overall improvement in psychopathology. However, clozapine was numerically superior to risperidone on PANSS total scores and PANSS positive, negative, excitement, and cognitive factors. Extrapyramidal side effects were minimal for clozapine, whereas some were present for risperidone. Patients taking risperidone improved significantly in the beginning stages of the study and remained stable thereafter. Patients taking clozapine showed a gradual improvement that occurred over the entire length of the trial. Neurocognitive measures showed minimal improvement and did not differentiate between the 2 medication groups.

Conclusion: Both clozapine and risperidone were comparably effective across a wide spectrum of psychopathologic measures. While the efficacy of clozapine was only numerically superior to that of risperidone, it was associated with fewer extrapyramidal side effects and with progressive improvement over the 12-week treatment period, suggesting that in longer trials clozapine may prove to be superior to risperidone in neuroleptic-refractory patients.