Cognitive change and antipsychotic medications: Results from a pragmatic rater-blind RCT

Cognitive impairment is a core aspect of psychotic disorders and difficult to treat. Atypical antipsychotics (AAs) might have differential effects on cognitive impairment, but rigid study designs and selective sampling limit the generalizability of existing findings. This pragmatic, semi-randomized, industry-independent study aimed to investigate and compare the effect of amisulpride, aripiprazole and olanzapine on cognitive performance in psychosis over a 12-month period controlling for diagnostic group. This sub study of the BeSt InTro study recruited adults with ongoing psychosis in the schizophrenia spectrum of disorders (ICD-10 diagnoses F20-F23, F25, F28 or F29; n = 104) from Bergen and Stavanger, Norway; and Innsbruck, Austria. Participants were randomized to amisulpride, aripiprazole, or olanzapine and they completed neuropsychological assessments at baseline, 6 weeks, 6 and 12 months. The test battery targeted working memory, verbal ability, and processing speed. We used Longitudinal mixed effect (LME) models to assess cognitive change for intention to treat (ITT) and per protocol (PP) medication groups, as well as comparing cognitive performance between F20 and non-F20 participants. The sample baseline global cognitive performance t-score was 42.20. Global performance improved significantly to every follow-up, including for the F20 group. There were however no significant differences in cognitive change over time between neither ITT nor PP medication groups.