Changes in cognitive functioning with risperidone and olanzapine treatment: A large-scale, double-blind, randomized study

Objective: The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a randomized, double-blind trial. Method: Three hundred and seventy-seven patients were randomly assigned to receive 2-6 mg/day of risperidone or 5-20 mg/day of olanzapine for 8 weeks. Cognitive function was assessed with a focused cognitive assessment battery; in addition, extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale (ESRS), and the positive and negative syndrome scale (PANSS) was rated for all patients. Results: Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test, the trail-making test, the California verbal learning test, the continuous performance test, and some aspects of verbal fluency and spatial working memory. No differences in the effects of the drugs on any of the cognitive tests were noted. Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects. Conclusions: Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning. Previous reports of greater benefits of olanzapine over risperidone in a small-sample pilot study were not substantiated. These results are not due in general to changes in clinical symptoms or movement disorders, suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia.