Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. Clozapine and risperidone in chronic schizophrenia: effects on symptoms, parkinsonian side effects, and neuroendocrine response. Risperidone versus clozapine in treatment-resistant chronic schizophrenia: a randomized double-blind study. The Risperidone Study Group.
Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage. Clozapine and risperidone were the first two "second-generation" antipsychotic drugs approved for schizophrenia. There is currently little information about their comparative efficacy from head-to-head clinical trials. The purpose of this study was to examine the comparative efficacy of clozapine and risperidone for positive and negative symptoms, depression, parkinsonian side effects, and indexes of neuroendocrine function in schizophrenic patients who met a priori criteria for partial response to traditional neuroleptic agents.
                After a baseline fluphenazine treatment period, 29 patients participated in a 6-week, double-blind, parallel-group comparison of the effects of these agents.
                Clozapine was superior to risperidone for positive symptoms and parkinsonian side effects, but there were no significant differences between the drugs on two measures of negative symptoms, Brief Psychiatric Rating Scale total scores, and depression scores. The clozapine patients, but not the risperidone patients, demonstrated significant reductions from the fluphenazine baseline in positive symptoms, total symptoms, and depression. In addition, clozapine produced fewer effects on plasma prolactin than risperidone or fluphenazine. The mean daily doses during week 6 of the trial were 403.6 mg of clozapine and 5.9 mg of risperidone.
                The findings from this study indicate that these drugs have both important differences and similarities in their comparative efficacy in chronically ill, partially responsive patients with schizophrenia. Further research on second-generation antipsychotic drugs in this patient population that addresses key methodological issues, such as optimal dose and treatment duration, are needed. The purpose of this study was to compare the short-term efficacy and safety of risperidone and clozapine in treatment-resistant chronic schizophrenic patients.
                In a controlled double-blind, multicenter study, 86 inpatients with chronic schizophrenia (DSM-III-R), who were resistant to or intolerant of conventional neuroleptics, were randomly assigned to receive risperidone or clozapine for 8 weeks after a 7-day washout period. After a 1-week dose-titration phase, doses were fixed at 6 mg/day of risperidone and 300 mg/day of clozapine for 1 week and then adjusted according to each patient's response. The final mean doses were 6.4 mg/day of risperidone and 291.2 mg/day of clozapine. Treatment efficacy and safety were evaluated with several well-known rating scales.
                Both risperidone and clozapine significantly reduced the severity of psychotic symptoms (scores on the Positive and Negative Syndrome Scale and the Clinical Global Impression scale) from baseline, with no significant between-group differences. At endpoint, 67% of the risperidone group and 65% of the clozapine group were clinically improved (reduction of 20% or more in total Positive and Negative Syndrome Scale score). Risperidone appeared to have a faster onset of action. In both groups extrapyramidal symptoms and other adverse events were few, and their severity was generally mild. Neither group showed evidence of a relation between drug plasma concentrations and clinical effectiveness.
                Risperidone was well tolerated and as effective as medium doses of clozapine in patients with chronic schizophrenia who had been resistant to or intolerant of conventional neuroleptics.
The equivalence of clozapine and risperidone for treatment resistant schizophrenia cannot yet be assumed and there seems to be little to chose between risperidone and both olanzapine and amisulpiride. The research is limited in many respects, and longer term studies measuring clinically important outcomes, including service use and quality of life are needed to judge the comparative value of the various atypical drugs.