title: Comparison of cognitive performances during a placebo period and an atypical antipsychotic treatment period in schizophrenia: critical examination of confounds.
abstract: Although previous studies report cognitive improvement following atypical antipsychotic administration in schizophrenia (SC), few placebo-controlled within-subject studies with examination of confounds (symptom reduction, cooperation, learning, and outliers) have been reported. The present study examines the effects of atypicals and confounds upon cognition in SC. The hypothesis tested was that relative to placebo, atypicals as a general class of medication would elicit cognitive improvement in SC. In all, 19 patients with SC (15 males) completed the double-blind, counterbalanced, randomized within-subject study of the effects of atypical antipsychotics (risperidone, clozapine, olanzapine, or quetiapine) vs placebo administration upon cognitive performance in the domains of executive function, attention, memory, language, visual perception, and general intellect. Significant cognitive improvement during atypical antipsychotic administration relative to placebo withdrawal occurred in most cognitive domains with robust improvements in intelligence (p=0.001), memory (p=0.0009), and fluency (p <0.002) even after outliers and unmotivated performances were excluded. These findings suggest that relative to placebo withdrawal, atypicals improve cognitive performance in SC. However, this finding may not be specific to atypicals, since analogous studies of typicals have not been performed.
authors.affiliation: Clinical Brain Disorders Branch, National Institute of Mental Health/NIH, Building 10 Room 4N202, MSC 1379, Bethesda, MD 20892, USA. weickert@intra.nimh.nih.gov
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Weickert
authors.forename: Terry E
authors.initials: TE
authors.lastname: Goldberg
authors.forename: Stefano
authors.initials: S
authors.lastname: Marenco
authors.forename: Llewellyn B
authors.initials: LB
authors.lastname: Bigelow
authors.forename: Michael F
authors.initials: MF
authors.lastname: Egan
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011618:Psychotic Disorders / Q000188:drug therapy; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology
chemical_list: D014150:Antipsychotic Agents