Objective: To assess the cognitive effects of sertindole augmentation in clozapine-treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial.
Method: A 12-week, double-blinded, randomized, placebo-controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine.
Results: Participants displayed substantial cognitive deficits, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative Syndrome (PANSS) subscales, Global Assessment of Functioning subscale (GAF-F) and Clinical Global Impression (CGI) with 20 neurocognitive indices was conducted, but no significant correlations were found. Second, we tested change from baseline to endpoint for the PANSS, GAF-F, and CGI, vs. the concomitant changes in cognitive test performance, and found no significant correlations.
Conclusion: The clozapine-treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect on cognition of augmenting clozapine treatment with another antipsychotic drug.
Trial registration: ClinicalTrials.gov NCT00345982.
© 2012 John Wiley & Sons A/S.