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 ¼ 0.001), memory (p ¼ 0.0009), and fluency (po0.002) 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.

Effects of Antipsychotic Drugs on Neurogenesis in the Forebrain of the Adult Rat

“…We found that treatment with an atypical but not a typical APD increased the numbers and densities of newly generated cells in the PFC and striatum. The ability of olanzapine but not haloperidol to increase the generation of new cells in the cortex is consistent with the therapeutic profiles of these drugs: many but not all studies suggest that atypical APDs are more effective in reducing negative symptoms and improving cognitive function, both of which have been associated with PFC dysfunction (Meltzer and McGurk, 1999;Geddes et al, 2000;Wahlbeck et al, 2000;Bilder et al, 2002;Conley and Kelly, 2002;Bobes et al, 2003;Davis et al, 2003a, b;Gur et al, 2003;Leucht et al, 2003;Lieberman et al, 2003b;Moncrieff, 2003;Rosenheck et al, 2003;Weickert et al, 2003;Woerner et al, 2003).…”

Circumstances Under Which Practice Does Not Make Perfect: A Review of the Practice Effect Literature in Schizophrenia and Its Relevance to Clinical Treatment Studies

“…Crossover studies may be prone to complex carry-over effects, drug withdrawal effects, and time one-time two differences (Weickert et al, 2003).…”

Schizophrenic patients exhibit hyper-reflexivity in a semantic categorical priming task

“…We found no differences in performance between the typical, atypical, and unmedicated subjects, which we believe is simply due to a low number of subjects in the atypical and unmedicated groups. There is much evidence to support the idea that atypical antipsychotics help certain types of cognitive processes, including verbal fluency, verbal memory, general intelligence, continuous performance test, and spatial working memory, among others (Harvey, Green, McGurk, & Meltzer, 2003;Weickert et al, 2003). It has also been found that certain atypical medications (e.g., olanzapine, risperidone, and quetiapine) have a more advantageous effect than typical medications (e.g., haloperidol) on such cognitive processes as attention, motor function, visuospatial tasks, immediate recall tasks, verbal memory, and verbal fluency (Keefe et al, 2006;Purdon, Malla, Labelle, & Lit, 2001;Velligan et al, 2002).…”