An open comparison of clozapine and risperidone in treatment-resistant schizophrenia

Background: Clozapine and risperidone are used in treatment-resistant schizophrenia. At present, there are few reported comparisons of these drugs in this population. We report on a consecutive series of treatment-resistant schizophrenics given either clozapine or risperidone in open clinical trials. Method: Subjects were treated with clozapine (n=57) or risperidone (n=29). Pretreatment GAF, CGI, and PANSS scores did not differ between the groups, nor did demographic variables including age, age at first hospitalization, years ill, number of previous hospitalizations, or gender. The mean treatment trial was 12.1 weeks, with mean doses of clozapine 420 mg, and risperidone 7.75 mg. The length of the trial did not differ significantly between the groups. Response was taken to be a 20% decrease in the PANSS score. Results: Using repeated measures ANOVA, PANSS total scores (F=5.3, p=0.02) and positive subscore (F=7.4, p=0.008) showed greater improvement in the clozapine group than the risperidone group, while other PANSS subscores showed a trend toward greater improvement with clozapine. The PANSS-derived factors of excitement (F=6.7, p=0.01), psychosocial withdrawal (F=3.8, p=0.05), and psychomotor retardation (F=3.9, p=0.05) improved more in the group treated with clozapine. The GAF (F=10.9, p=0.0014), CGI (F=11.5, p=0.0011), and CGI improvement (p=0.0001) scores also improved more in the clozapine group. Of the clozapine group, 25 (44%) responded, while 8 (28%) of the risperidone group responded to treatment. Discussion: Clozapine had better efficacy in subjects with treatment-resistant schizophrenia compared to risperidone, although risperidone appears to yield better response rates than those previously reported for typical antipsychotics. Double-blind, controlled trials of risperidone are needed to establish its efficacy in treatment-resistant schizophrenia.