Randomized, Double-Blind, Controlled Trial of Risperidone Versus Clozapine in Patients With Chronic Schizophrenia

Abstract

This study compares the antipsychotic efficacy and the tolerability of risperidone and clozapine in patients with schizophrenia. Patients were randomized to double-blind treatment with risperidone, 4 mg (N = 20), risperidone, 8 mg (N = 19), or clozapine, 400 mg (N = 20), daily for 28 days. Efficacy was assessed by improvement of psychotic symptoms, measured on the Brief Psychiatric Rating Scale, and Clinical Global Impression. The tolerability was assessed by the Simpson and Angus scale for extrapyramidal side effects (EPS), the Association for Methodology and Documentation in Psychiatry (AMDP) scale for somatic side effects, spontaneous reports of adverse events, clinical laboratory assessments, and vital signs. All treatments reduced psychotic symptoms. The global tolerability was significantly better in the risperidone than in the clozapine-treated patients (p < 0.01). There were no differences between treatments on the AMDP scale. The most frequent spontaneously reported adverse effects were dizziness, fatigue, accommodation disturbance, and EPS in all treatment groups and increased salivation, mainly in the clozapine-treated patients. Although there were no changes in vital signs during risperidone treatment, clozapine was associated with a mean reduction in heart rate of 10 beats/minute. Risperidone tolerability at endpoint was classified as "very good" by 60 and 47% of patients treated with risperidone, 4 and 8 mg daily, respectively; the corresponding figure in clozapine-treated patients was 30%. The results suggest that risperidone is at least as effective as an antipsychotic as clozapine, providing a valuable new approach for the treatment of schizophrenia.

Advances in psychopharmacology -- schizophrenia

“…Nonetheless, these do show clozapine to be an effective antipsychotic agent in this situation, though interestingly there is no more than a hint of better efficacy than a standard drug 14 -28 . The same conclusion of essentially comparable efficacy in acute situations can be drawn from a more recent comparison with risperidone 29 .…”

A systematic review of atypical antipsychotic drugs in schizophrenia

“…Removing studies with > 25% attrition from the analysis (Klieser 1996, 47%; 264 Anand 1998, 42%; 111 Wahlbeck 2000, 30% 113 ) made no substantial difference to the results.…”

“…In the original review, 23 studies were identified for inclusion: Blin 1996, 251 Borison 1991, 252 Bouchard 1998, 253 Ceskova 1993, 254 Chouinard 1993, 255 Claus 1991, 256 Emsley 1995, 257 Hoyberg 1993, 258 Huttunen 1995, 259 Mahmoud 1998, 260 Marder 1994, 116 Mesotten 1991, 261 Min 1993, 262 Peuskens 1995, 263 Fleurot 1997, 62 Bondolfi 1998, 110 Anand 1998, 111 Breier 1999, 112 Wahlbeck 2000, 113 Tran 1997, 171 Klieser 1996, 264 Jones 1998, 193 Gureje 1998. 186 Data extraction sheets for these studies are presented in appendix 3.…”

Risperidone: Refining the Tools to Treat Schizophrenia

“…Three studies have been conducted comparing the therapeutic effects of risperidone to clozapine in the treatment of psychotic symptoms (7,25,37). Each of these investigations concluded that the medications were equally effective, but these findings are tempered somewhat by significant limitations in study design, including a small number of enrolled subjects and brief duration of treatment.…”