A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia

Objective: This prospective, double-blind, multicenter, parallel-group stud y compared the efficacy and safety of therapeutic doses of clozapine and ri speridone in patients with severe chronic schizophrenia and poor previous t reatment response. Method: Male or female patients aged 18-65 years who met DSM-IV criteria fo r schizophrenia and study requirements for poor previous treatment response (N= 273) were randomly assigned to double-blind treatment with either cloz apine or risperidone administered over 12 weeks in increasing increments. T he primary efficacy measures were the magnitude of improvement in Brief Psy chiatric Rating Scale (BPRS) and Clinical Global impression (CGI) scores. A dverse events were recorded throughout the study. Results. The magnitude of improvement in mean BPRS and CGI scores from base -line to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in fav or of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile w as similar for both treatment groups, with a lower risk of extrapyramidal s ymptoms in the clozapine group. Conclusions: Clozapine showed superior efficacy over risperidone in this pa tient population. Both treatments were equally well tolerated as demonstrat ed through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.