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

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

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

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

Conclusion: Both clozapine and risperidone were comparably effectiveacross a wide spectrum of psychopathologic measures. While the efficacy of clozapine wasonly numerically superior to that of risperidone, it was associated with fewerextrapyramidal side effects and with progressive improvement over the 12-week treatmentperiod, suggesting that in longer trials clozapine may prove to be superior to risperidonein neuroleptic-refractory patients.