Olanzapine has better efficacy compared to risperidone for treatment of negative symptoms in schizophrenia

Objective: The safety and efficacy profile of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice. Methods: Subjects (n = 71) who met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for schizophrenia were randomly assigned to receive 2-8 mg/day of risperidone (mean modal dose = 5.5 mg/day) or 5-20 mg/day of olanzapine (mean modal dose = 14.4 mg/day) for 1 year. Results: The two study groups were similar at baseline in all aspects. Seventy-four percent of the participants completed the trial, with no between-differences in the proportion of dropouts. Olanzapine group showed significantly greater improvement in negative symptoms in assessments at 3rd, 6th, 9th, and 12th months (P = 0.05, 0.00, 0.00, and 0.00, respectively). Clinical global impression of severity (CGI-S) scores were consistently lower in the olanzapine group at 3rd, 6th, and 9th months (P = 0.01, 0.03, and 0.05, respectively) as measured by positive and negative symptom scale (PANSS). Total scores on PANSS, positive symptoms, general psychopathology, and CGI improvement showed comparable improvement at 3rd, 6th, 9th, and 12th months of follow-up (all subjects, including dropouts). Severity of extrapyramidal symptoms was low in both groups, with no between-group differences. Mean change in body weight, fasting blood sugar, and fasting cholesterol was comparable in both groups. Risperidone group had significant hyperprolactinemia after one year (P = 0.03). Conclusions: Both treatments were well-tolerated and efficacious. Greater reductions in severity of the illness and negative symptoms were seen with olanzapine consistently through 1 year. The frequency and severity of extrapyramidal symptoms were negligible and similar in the two treatment groups. Weight gain, hyperlipidemia, and hyperglycemia were comparable in both groups. Risperidone produced significant hyperprolactinemia.