Clinical and Neurocognitive Effects of Clozapine and Risperidone in Treatment-Refractory Schizophrenic Patients: A Prospective Study
J Clin Psychiatry 1998;59(10):521-527
© Copyright 2015 Physicians Postgraduate Press, Inc.
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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
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.