Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia - An observational 9-year follow-up study

Schizophr Res. 2014 Sep;158(1-3):134-41. doi: 10.1016/j.schres.2014.06.035. Epub 2014 Jul 15.


Background: The association between the course of cognition and long-term antipsychotic medication in schizophrenia remains unclear. We analysed the association between cumulative lifetime antipsychotic medication dose and change of verbal learning and memory during a 9-year follow-up.

Method: Forty schizophrenia subjects and 73 controls from the Northern Finland Birth Cohort 1966 were assessed by California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data on the lifetime antipsychotic doses in chlorpromazine equivalents were collected. The association between antipsychotic dose-years and baseline performance and change in CVLT was analysed, controlling for baseline performance, gender, age of onset and severity of illness.

Results: Higher antipsychotic dose-years by baseline were significantly associated with poorer baseline performance in several dimensions of verbal learning and memory, and with a larger decrease in short-delay free recall during the follow-up (p=0.031). Higher antipsychotic dose-years during the follow-up were associated with a larger decrease of immediate free recall of trials 1-5 during the follow-up (p=0.039). Compared to controls, decline was greater in some CVLT variables among those using high-doses, but not among those using low-doses.

Conclusion: This is the first report of an association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up. The use of high doses of antipsychotics may be associated with a decrease in verbal learning and memory in schizophrenia years after illness onset. The results do not support the view that antipsychotics in general prevent cognitive decline or promote cognitive recovery in schizophrenia.

Keywords: California Verbal Learning Test; Cognition; Follow-up; Longitudinal; Psychosis; Treatment.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / adverse effects*
  • Chlorpromazine / administration & dosage
  • Chlorpromazine / adverse effects
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Female
  • Finland
  • Follow-Up Studies
  • Humans
  • Male
  • Memory / drug effects*
  • Neuropsychological Tests
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology*
  • Speech Perception / drug effects*
  • Verbal Learning / drug effects*


  • Antipsychotic Agents
  • Chlorpromazine