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Atypical antipsychotic drugs and risk of ischaemic stroke: population based retrospective cohort study

BMJ 2005; 330 doi: (Published 24 February 2005) Cite this as: BMJ 2005;330:445
  1. Sudeep S Gill (gills{at}, adjunct scientist1,
  2. Paula A Rochon, assistant director2,
  3. Nathan Herrmann, head3,
  4. Philip E Lee, geriatrician6,
  5. Kathy Sykora, senior biostatistician1,
  6. Nadia Gunraj, biostatistician1,
  7. Sharon-Lise T Normand, professor of biostatistics7,
  8. Jerry H Gurwitz, professor8,
  9. Connie Marras, neurologist4,
  10. Walter P Wodchis, scientist5,
  11. Muhammad Mamdani, scientist1
  1. 1Institute for Clinical Evaluative Sciences, 2075 Bayview Avenue, Toronto, ON, Canada
  2. 2Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Toronto
  3. 3 Division of Geriatric Psychiatry, Department of Psychiatry, Sunnybrook and Women's College Health Sciences Centre, Toronto,
  4. 4Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto
  5. 5 Toronto Rehabilitation Institute, Toronto,
  6. 6Division of Geriatric Medicine, University of British Columbia, Vancouver, BC, Canada
  7. 7 Department of Health Care Policy, Harvard Medical School and Harvard School of Public Health, Boston, MA, USA,
  8. 8 Meyers Primary Care Institute, University of Massachusetts Medical School, Worcester, MA
  1. Correspondence to: S S Gill, Room 1-152, Chapel Wing, St Mary's of the Lake Hospital, 340 Union Street, Kingston, ON, Canada K7L 5A2
  • Accepted 1 December 2004


Objective To compare the incidence of admissions to hospital for stroke among older adults with dementia receiving atypical or typical antipsychotics.

Design Population based retrospective cohort study.

Setting Ontario, Canada.

Patients 32 710 older adults (≤ 65 years) with dementia (17 845 dispensed an atypical antipsychotic and 14 865 dispensed a typical antipsychotic).

Main outcome measures Admission to hospital with the most responsible diagnosis (single most important condition responsible for the patient's admission) of ischaemic stroke. Observation of patients until they were either admitted to hospital with ischaemic stroke, stopped taking antipsychotics, died, or the study ended.

Results After adjustment for potential confounders, participants receiving atypical antipsychotics showed no significant increase in risk of ischaemic stroke compared with those receiving typical antipsychotics (adjusted hazard ratio 1.01, 95% confidence interval 0.81 to 1.26). This finding was consistent in a series of subgroup analyses, including ones of individual atypical antipsychotic drugs (risperidone, olanzapine, and quetiapine) and selected subpopulations of the main cohorts.

Conclusion Older adults with dementia who take atypical antipsychotics have a similar risk of ischaemic stroke to those taking typical antipsychotics.


  • Contributors SSG, PAR, NH, PEL, and MM conceived the study. All authors contributed to the study design. KS, NG, and SSG performed the data analysis. SSG wrote the initial draft, and all authors critically revised the manuscript. PAR and MM were overseers of the research network. SSG will act as guarantor for the paper.

  • Funding SSG was supported by a Canadian Institutes of Health Research postdoctoral fellowship and the Annie Kirshenblatt Memorial scholarship. PAR is supported by a Canadian Institutes of Health Research Investigator Award. Eli Lilly Canada partly supported PEL's behavioural neurology fellowship. This work was supported by a Canadian Institutes of Health Research Chronic Disease New Emerging Team programme grant (NET 54010). The NET programme receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada, and the Canadian Institutes of Health Research Institutes of Nutrition, Metabolism, and Diabetes, and Circulatory and Respiratory Health. MM was supported in part by a New Investigator Award through the NET programme.

  • Conflict of interest NH has received research support and speaker's honoraria from Janssen-Ortho, Eli Lilly, Novartis, Pfizer, and Astra Zeneca, manufacturers of atypical antipsychotics.

  • Ethical approval This study was approved by the ethics review board of Sunnybrook and Women's College Health Sciences Centre.

  • Accepted 1 December 2004
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