Effect of second-generation antipsychotics on cognition: Current issues and future challenges

S. Kristian Hill, Jeffrey R. Bishop, Donna Palumbo, John A. Sweeney

Research output: Contribution to journalReview articlepeer-review

177 Scopus citations


Generalized cognitive impairments are stable deficits linked to schizophrenia and key factors associated with functional disability in the disorder. Preclinical data suggest that second-generation antipsychotics could potentially reduce cognitive impairments; however, recent large clinical trials indicate only modest cognitive benefits relative to first-generation antipsychotics. This might reflect a limited drug effect in humans, a differential drug effect due to brain alterations associated with schizophrenia, or limited sensitivity of the neuropsychological tests for evaluating cognitive outcomes. New adjunctive procognitive drugs may be needed to achieve robust cognitive and functional improvement. Drug discovery may benefit from greater utilization of translational neurocognitive biomarkers to bridge preclinical and clinical proof-of-concept studies, to optimize assay sensitivity, enhance cost efficiency, and speed progress in drug development.

Original languageEnglish (US)
Pages (from-to)43-57
Number of pages15
JournalExpert review of neurotherapeutics
Issue number1
StatePublished - Jan 2010


  • Antipsychotic medication
  • Biomarker
  • Cognition
  • Neuropsychology
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Pharmacology (medical)


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