DOUBLE-BLIND COMPARISON OF OLANZAPINE VERSUS RISPERIDONE IN THE TREATMENT OF SCHIZOPHRENIA AND OTHER PSYCHOTIC DISORDERS

Olanzapine and risperidone, both second-generation antipsychotic agent s, represent two different pharmacologic strategies. Although they sha re some in vitro properties, they differ by virtue of their chemical s tructure, spectrum of receptor binding affinities, animal neuropharmac ology, pharmacokinetics, and in vivo neuroimaging profile. Based on su ch differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothes is, an international, multicenter, double-blind, parallel-group, 28-we ek prospective study was conducted with 339 patients who met DSM-TV cr iteria for schizophrenia, schizophreniform disorder, or schizoaffectiv e disorder. Results of the study indicated that both olanzapine and ri speridone were safe and effective in the management of psychotic sympt oms. However, olanzapine demonstrated significantly greater efficacy i n negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (greater than or equal to 40 % decrease in the Positive and Negative Syndrome Scale total score). F urthermore, a statistically significantly greater proportion of the ol anzapine-treated than risperidone-treated patients maintained their re sponse at 28 weeks based on Kaplan-Meier survival curves. The incidenc e of extrapyramidal side effects, hyperprolactinemia, and sexual dysfu nction was statistically significantly lower in olanzapine-treated tha n risperidone-treated patients. In addition, statistically significant ly fewer adverse events were reported by olanzapine-treated patients t han by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a control led, clinical investigation. Olanzapine seemed to have a risk-versus-b enefit advantage.