Rationale: Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials.
Objectives: To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology.
Methods: We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia.
Results: Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047).
Conclusions: Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.