Neurocognitive effects of first- and second-generation antipsychotic drugs in early-stage schizophrenia: a naturalistic 12-month follow-up study.

The study aimed to assess the cognitive effects of first- and second-generation antipsychotics on neurocognition under naturalistic treatment conditions. In a 12-month, open-label, multicenter study, 698 patients with early-stage schizophrenia (duration of illness ≤5 years) were prescribed chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, or aripiprazole monotherapy. A neuropsychological battery including tests of attention, processing speed, learning/memory, and executive functioning was administered at baseline, 6- and 12-months. The primary outcome was change in a cognitive composite score after 12-months of treatment. At 12 months, treatment resulted in mild to moderate neurocognitive improvements of z=0.32 for chlorpromazine, 0.33 for sulpiride, 0.43 for clozapine, 0.51 for risperidone, 0.69 for olanzapine, 0.64 for quetiapine and 0.46 for aripiprazole. However, the olanzapine and quetiapine groups demonstrated greater improvement in the composite score and processing speed than did the chlorpromazine and sulpiride groups. Both first- and second-generation antipsychotics may improve cognitive function in patients with early-stage schizophrenia. Given that some neurocognitive improvement is attributable to a practice effect, any improvement is likely to be in the range of a small effect size.