Intended for healthcare professionals


Exposure to antipsychotics and risk of stroke: self controlled case series study

BMJ 2008; 337 doi: (Published 28 August 2008) Cite this as: BMJ 2008;337:a1227
  1. Ian J Douglas, research fellow,
  2. Liam Smeeth, professor of clinical epidemiology
  1. 1Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT
  1. Correspondence to: I Douglas ian.douglas{at}
  • Accepted 30 June 2008


Objectives To investigate the association between use of typical and atypical antipsychotic drugs and incidence of stroke in patients with and without dementia.

Design Self controlled case series.

Setting UK based electronic primary care records in the general practice research database (GPRD).

Participants All patients registered in the database with a recorded incident stroke and at least one prescription for any antipsychotic drug before the end of 2002: 6790 eligible participants were identified and included in the final analysis.

Main outcome measures Rate ratio for stroke in periods of time exposed to antipsychotics compared with unexposed periods.

Results Use of any antipsychotic drug was associated with a rate ratio for stroke of 1.73 (95% confidence interval 1.60 to 1.87): 1.69 (1.55 to 1.84) for typical antipsychotics and 2.32 (1.73 to 3.10) for atypical antipsychotics. In patients receiving any antipsychotic drug, the rate ratios were 3.50 (2.97 to 4.12) for those with dementia and 1.41 (1.29 to 1.55) for those without dementia.

Conclusions All antipsychotics are associated with an increased risk of stroke, and the risk might be higher in patients receiving atypical antipsychotics than those receiving typical antipsychotics. People with dementia seem to be at a higher risk of an associated stroke than people without dementia and use of antipsychotics should, when possible, be avoided in these patients.


  • Contributors: IJD and LS were the sole contributors and authors of this study. Both authors played a substantial role in developing the research question, obtaining the data, interpreting the results, and preparing the manuscript and are joint guarantors. IJD carried out the analysis.

  • Funding: LS is supported by a Wellcome Trust senior research fellowship in clinical science. Data from the general practice research database were made available through the access for UK academics via Medical Research Council agreement.

  • Competing interests: None declared.

  • Ethical approval: Independent scientific advisory group of the general practice research database and the London School of Hygiene and Tropical Medicine ethics committee.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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