Ziprasidone and Cognition: The Evolving Story

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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 of antipsychotic medications is increasingly focusing on the possible benefits of these agents on cognitive function. Although data are limited, it appears that atypical antipsychotics consistently improve cognitive function to a greater extent than do older, conventional agents. This review focuses on the atypical agent ziprasidone and its effects on cognitive function. The most recent data on the cognitive effects of ziprasidone come from a comparative trial with olanzapine (40–80 mg b.i.d. and 5–15 mg q.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, ziprasidonetreated patients demonstrated significant improvements in multiple cognitive domains—such as episodic memory, attention/vigilance, executive function, and visuomotor speed—that are generally associated with improved functional outcome. In the switching studies, path analysis indicated that improvement on the Positive and Negative Syndrome Scale (PANSS) cognitive subscale directly affected changes on the PANSS anxiety–depression cluster and a PANSS "prosocial" subscale composed of items related to social engagement. Improvement in cognitive function observed with ziprasidone may have implications for long-term patient outcomes.

J Clin Psychiatry 2003;64(suppl 19):33-39