Ziprasidone and Cognition: The Evolving Story

Cognitive impairment, a central characteristic of schizophrenia, can profoundly limit patients’ ability to acquire or maintain skills needed for adequate functioning. Thus, research on the efficacy ofantipsychotic medications is increasingly focusing on the possible benefits of these agents on cognitivefunction. Although data are limited, it appears that atypical antipsychotics consistently improvecognitive function to a greater extent than do older, conventional agents. This review focuses on theatypical agent ziprasidone and its effects on cognitive function. The most recent data on the cognitiveeffects of ziprasidone come from a comparative trial with olanzapine (40-80 mg b.i.d. and 5-15 mgq.d., respectively) and from 3 studies in which patients were switched to ziprasidone (40-160 mg/day)because of suboptimal efficacy or tolerability with other antipsychotics. In general, ziprasidonetreatedpatients demonstrated significant improvements in multiple cognitive domains—such as episodicmemory, attention/vigilance, executive function, and visuomotor speed—that are generally associatedwith improved functional outcome. In the switching studies, path analysis indicated thatimprovement on the Positive and Negative Syndrome Scale (PANSS) cognitive subscale directly affectedchanges on the PANSS anxiety-depression cluster and a PANSS “prosocial” subscale composedof items related to social engagement. Improvement in cognitive function observed with ziprasidonemay have implications for long-term patient outcomes.