Cognitive improvement in schizophrenic patients does not require a serotonergic mechanism: randomized controlled trial of olanzapine vs amisulpride.
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.
Wagner
Michael
M
Department of Psychiatry, University of Bonn, Bonn, Germany. Michael.Wagner@ukb.uni-bonn.de
Quednow
Boris B
BB
Westheide
Jens
J
Schlaepfer
Thomas E
TE
Maier
Wolfgang
W
Kühn
Kai-Uwe
KU
D000293:Adolescent; D000328:Adult; D000368:Aged; D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001288:Attention / Q000187:drug effects; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects; D008875:Middle Aged; D009483:Neuropsychological Tests; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D012701:Serotonin / Q000502:physiology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013469:Sulpiride / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D014706:Verbal Learning / Q000187:drug effects
D000077582:Amisulpride; D014150:Antipsychotic Agents; D001569:Benzodiazepines; D000077152:Olanzapine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013469:Sulpiride