Effect of adjunctive treatment with aripiprazole to atypical antipsychotics on cognitive function in schizophrenia patients

Second-generation antipsychotics yield only a modest improvement in cognitive benefit compared to first-generation antipsychotics. Aripiprazole, which is a partial dopamine D2 receptor agonist, may have an impact on cognitive dysfunction in patients with schizophrenia. This study administered aripiprazole or placebo to 36 outpatients with schizophrenia also receiving risperidone or olanzapine for 12 weeks in a double-blind, randomized, placebo-controlled study. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia (BACS) just prior to drug administration as well as 12 weeks after. The PANSS and UKU side effect rating scales were used to evaluate the clinical response to additional treatment with aripiprazole. In a primary analyses, ANCOVA showed that there was an interaction between the treatment group and time for verbal fluency (p < 0.05), but not for any domain in BACS, PANSS or UKU side effect rating scales. Upon secondary analysis, however, the ameliorative change in motor speed as assessed by the BACS (p < 0.05) for those receiving aripiprazole was greater than that for the placebo group, whereas deterioration in verbal fluency (p < 0.01) and executive function (p < 0.01) in those receiving aripiprazole was significantly greater than in the placebo group. These results suggest that adjunctive treatment with aripiprazole improves motor speed but worsens some cognitive functions. It is likely that these effects are due to the dopamine D2 antagonistic effect of aripiprazole.