¹Department of Psychiatry, University of Bonn, Bonn, Germany

Correspondence: Dr Michael Wagner, Department of Psychiatry, University of Bonn, Sigmund Freud-Strasse 25, 53105 Bonn, Germany. Tel: +49 228 287 6377; Fax +49 228 287 6097; E-mail: Michael.Wagner@ukb.uni-bonn.de

Received 30 July 2004; Revised 15 October 2004; Accepted 21 October 2004; Published online 1 December 2004.

Abstract

Combined serotonin-2A (5-HT_2A) and dopamine-2 (D₂) receptor blockade has been proposed as a candidate mechanism by which second-generation antipsychotics (SGAs) improve both cognition and negative symptoms in schizophrenic patients, in contrast to antipsychotics of the first generation. The SGA amisulpride, however, only binds to D₂/D₃ receptors, which makes it an interesting tool to test this assumption. In a randomized controlled trial, 52 schizophrenic patients were allocated to treatment with either olanzapine (10–20 mg/day) or amisulpride (400–800 mg/day). A comprehensive neuropsychological test battery and clinical ratings were used to assess participants at inclusion and after 4 and 8 weeks. Cognitive improvements of moderate size were observed, with effect sizes similar to those obtained in previous studies on the cognitive effects of SGAs. Importantly, amisulpride was not inferior to olanzapine for any cognitive domain. Combined 5-HT_2A/D₂ receptor blockade is probably not necessary for cognitive improvement by SGAs.