A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia

Abstract

Cognitive impairment represents a core feature of schizophrenia and a major impediment to social and vocational rehabilitation. First generation antipsychotic (FGA) medications do not elicit robust cognitive changes, but over the past 15 years a number of studies have claimed benefits from various Second Generation Antipsychotics (SGAs). This contention was evaluated in two meta-analyses of the cognitive changes elicited by the SGA treatments clozapine, olanzapine, quetiapine, and risperidone. The first meta-analysis of twelve double blind, random assignment studies indicated that SGA treatments improved cognitive performance on tests of learning, processing speed, verbal fluency, and delayed recall to a greater extent than FGAs. The postulated cognitive benefits from SGAs, and a preliminary analysis of differential effects within the SGA class, were then assessed in a larger meta-analysis of forty-one studies that used experimental designs without random assignment to double-blind treatment, or did not include an FGA comparator. The second analysis confirmed the improvements observed in double blind, random assignment studies and further identified benefits in vigilance, working memory, cognitive flexibility and abstraction, visuospatial skills, and motor skills. Differences between SGAs were noted within the Vigilance and Verbal Fluency domains. After a consideration of the improvements expected from practice effects, significant improvements on tests of working memory, verbal fluency, motor skills, and delayed recall remained. Thus, the cognitive benefits of SGAs appear valid. Nonetheless, the magnitude of improvement is generally small, less than half a standard deviation, and their relevance to functional outcome remains debatable.