A randomized, placebo-controlled, double-blind trial of augmentation of clozapine with risperidone

Incomplete or partial improvement of symptoms following treatment with clozapine is not infrequent in chronic schizophrenia. Commonly, patients are prescribed an additional antipsychotic medication, although there is little evidence from controlled studies of the efficacy of this practice. We performed a placebo controlled study of risperidone augmentation of partial response to clozapine in schizophrenia. Subjects were required to be treated with clozapine at a stable dose of 400 mg or more for at least 12 weeks prior to screening. Concurrent psychotropic medications were discontinued at least 2 weeks prior to study entry. At baseline (on clozapine), the total PANSS score was 97.1 (n=69), and following one week of placebo augmentation run-in the total PANSS score was 99.6. Subjects were randomized to continuation of clozapine+placebo, or to clozapine+risperidone 3.0 mg for 8 weeks. Clozapine doses were unchanged. The study completion rate was 94% (n=65). Using a last observation carried forward approach, the total PANSS score at the end of the double blind phase was 87.7- there were no statistically significant differences between the placebo- and the risperidone augmentation groups. According to a 20% decline in total PANSS score approach to categorize subjects as responders, the rates of response were 26% (n=9/35) in the placebo augmentation group, and 18% (6/34) in the risperidone augmentation group. Addition of the requirement of a CGI score of 3 or less to define treatment response resulted in a rate of 11% (4/35) in the placebo augmentation group, and 3% (1/34) in the risperidone augmentation group. Addition of risperidone to clozapine does not appear to offer significant advantages in reducing the symptoms of schizophrenia in patients with poor or incomplete response to clozapine alone. Supported by the Stanley Medical Research Institute.