Neurocognitive effectiveness of quetiapine, olanzapine, risperidone, and ziprasidone: a pragmatic, randomized trial

Cognitive effects of second generation antipsychotics (SGAs) are indicated in efficacy studies but the generalizability of the results may be limited by rigid designs and selected samples. The aim of this naturalistic, industry-independent study is to investigate whether differential neurocognitive effectiveness can be found among olanzapine, quetiapine, risperidone, and ziprasidone in a clinically relevant sample with psychosis.

Adult patients acutely admitted to an emergency ward for psychosis were randomized to risperidone, olanzapine, quetiapine or ziprasidone and followed for up to 2 years. Participants were assessed repeatedly using the Positive and Negative Syndrome Scale and a repeatable neurocognitive test battery.

A total of 226 patients were included and 171 patients underwent neurocognitive assessments. The sample had a global cognitive performance score at baseline about one standard deviation below that of the general population. The ziprasidone group had the fastest increase in global functioning which was significantly superior to that of the olanzapine group for the entire follow-up period. Before 90 days, the quetiapine group had the fastest increase which was statistically superior to the olanzapine group.

Ziprasidone and quetiapine demonstrated superiority to olanzapine in increasing global neurocognitive performance in this naturalistic sample.