Comparative Efficacy of Risperidone and Clozapine in the Treatment of Patients With Refractory Schizophrenia or Schizoaffective Disorder: A Retrospective Analysis

Background: Clozapine is effective in upto 60% of patients with refractory schizophrenia, whereas theefficacy of risperidone remains unknown. This retrospective studyexamined the relative efficacy of these drugs in chronicallyinstitutionalized patients refractory to conventionalantipsychotic agents.

Method: A total of 24 patients who atdifferent time periods had received adequate trials of bothclozapine and risperidone and met our inclusion criteria forminimum dose and duration of each trial were included; forclozapine, a minimum dose of 300 mg/day had to be maintained forat least 12 weeks, and for risperidone, a minimum dose of 6mg/day for at least 6 weeks. Information obtained from systematicretrospective chart review was blindly rated by 2 psychiatristsusing the 7-point Clinical Global Impressions-Improvement (CGI-I)scale on overall clinical state and along specific symptomdomains of positive symptoms, negative symptoms, and aggressivebehavior.

Results: The mean ± SD dose was 520 ±94 mg/day for clozapine and 7.5 ± 2.2 mg/day for risperidone.Fourteen patients (58%) were classified as responders toclozapine, while 6 (25%) responded to risperidone (CGI-I score of1 or 2); on specific symptom domains, response rates to clozapinewere 38% (9/24) on positive symptoms, 29% (7/24) on negativesymptoms, and 71% (12/17) on aggressive behavior. Forrisperidone, response rates were 17% (4/24) on positive symptoms,8% (2/24) on negative symptoms, and 41% (7/17) on aggressivebehavior.

Conclusion: The results of this studysupport the utility of first giving a risperidone trial in atreatment algorithm for refractory patients because of its betterrisk/benefit profile compared with clozapine. Clozapine, however,remains our gold standard in the management of these patients.