Antipsychotic Drug Use and Mortality in Older Adults with Dementia

5 June 2007 | Volume 146 Issue 11 | Pages 775-786

Background: Antipsychotic drugs are widely used to manage behavioral and psychological symptoms in dementia despite concerns about their safety.

Objective: To examine the association between treatment with antipsychotics (both conventional and atypical) and all-cause mortality.

Design: Population-based, retrospective cohort study.

Setting: Ontario, Canada.

Patients: Older adults with dementia who were followed between 1 April 1997 and 31 March 2003.

Measurements: The risk for death was determined at 30, 60, 120, and 180 days after the initial dispensing of antipsychotic medication. Two pairwise comparisons were made: atypical versus no antipsychotic use and conventional versus atypical antipsychotic use. Groups were stratified by place of residence (community or long-term care). Propensity score matching was used to adjust for differences in baseline health status.

Results: A total of 27 259 matched pairs were identified. New use of atypical antipsychotics was associated with a statistically significant increase in the risk for death at 30 days compared with nonuse in both the community-dwelling cohort (adjusted hazard ratio, 1.31 [95% CI, 1.02 to 1.70]; absolute risk difference, 0.2 percentage point) and the long-term care cohort (adjusted hazard ratio, 1.55 [CI, 1.15 to 2.07]; absolute risk difference, 1.2 percentage points). Excess risk seemed to persist to 180 days, but unequal rates of censoring over time may have affected these results. Relative to atypical antipsychotic use, conventional antipsychotic use was associated with a higher risk for death at all time points. Sensitivity analysis revealed that unmeasured confounders that increase the risk for death could diminish or eliminate the observed associations.

Limitations: Information on causes of death was not available. Many patients did not continue their initial treatments after 1 month of therapy. Unmeasured confounders could affect associations.

Conclusions: Atypical antipsychotic use is associated with an increased risk for death compared with nonuse among older adults with dementia. The risk for death may be greater with conventional antipsychotics than with atypical antipsychotics.

Editors' Notes Context Recent reports suggest that antipsychotics are associated with increased risk for death in patients with dementia. Contribution This large, population-based study from Canada assessed the risk for death after dispensation of antipsychotics in older adults with dementia. New use of antipsychotics compared with nonuse was associated with increased risk for death at 30 days. Conventional agents were associated with higher risks than were atypical agents. Caution Sensitivity analyses showed that unmeasured confounders might diminish or erase observed associations. Implication Both conventional and atypical antipsychotics may be associated with an increased risk for death in elderly persons with dementia. —The Editors

 

Author and Article Information

From Queen's University, Kingston, Ontario, Canada; Institute for Clinical Evaluative Sciences and University of Toronto, Toronto, Ontario, Canada; Harvard Medical School and Harvard School of Public Health, Boston, Massachusetts; University of British Columbia, Vancouver, British Columbia, Canada; and Meyers Primary Care Institute of the University of Massachusetts Medical School, Fallon Clinic Foundation, and Fallon Community Health Plan, Worcester, Massachusetts.

Grant Support: By a Canadian Institutes for Health Research operating grant (no. 53124) and a Chronic Disease New Emerging Team program grant (no. 54010). The New Emerging Team program receives joint sponsorship from the Canadian Diabetes Association, the Kidney Foundation of Canada, the Heart and Stroke Foundation of Canada and the Canadian Institutes for Health Research Institutes of Nutrition, Metabolism & Diabetes and Circulatory & Respiratory Health. Dr. Gill is supported by an Ontario Ministry of Health and Long-Term Care Career Scientist Award. Dr. Bronskill is supported by a New Investigator Award through the New Emerging Team program. Dr. Anderson is supported by a Chair in Health Management Strategies from the University of Toronto. Dr. Rochon is supported by a Canadian Institutes for Health Research Investigator Award. Dr. Lee is supported by a fellowship grant from Eli Lilly.

Potential Financial Conflicts of Interest: Consultancies: P.E. Lee (Pfizer Canada, Janssen-Ortho), N. Herrmann (Janssen, Novartis, Pfizer Inc.); Honoraria: P.E. Lee (Pfizer Inc., Janssen-Ortho, Novartis), N. Herrmann (Janssen, Eli Lilly, Novartis, AstraZeneca); Expert testimony: N. Herrmann (Janssen); Grants received: P.E. Lee (Eli Lilly), N. Herrmann (Janssen).

Requests for Single Reprints: Sudeep S. Gill, MD, MSc, St. Mary's of the Lake Hospital, 340 Union Street, Kingston, Ontario K7L 5A2, Canada.

Current Author Addresses: Dr. Gill: St. Mary's of the Lake Hospital, 340 Union Street, Kingston, Ontario K7L 5A2, Canada.

Drs. Bronskill, Anderson, Bell, Fischer, and Rochon; Ms. Sykora; and Mr. Lam: Institute for Clinical Evaluative Sciences, G Wing, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

Dr. Normand: Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue, Boston, MA 02115-5899.

Dr. Lee: St. Paul's Hospital, 1081 Burrard Street, 9th Floor, Providence Building, Vancouver, British Columbia V6T 2B5, Canada.

Dr. Herrmann: Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario M4N 3M5, Canada.

Dr. Gurwitz: Meyers Primary Care Institute, 630 Plantation Street, Worcester, MA 01605.

Author Contributions: Conception and design: S.S. Gill, S.E. Bronskill, S.-L.T. Normand, G.M. Anderson, C.M. Bell, P.E. Lee, N. Herrmann, J.H. Gurwitz, P.A. Rochon.

Analysis and interpretation of the data: S.S. Gill, S.E. Bronskill, S.-L.T. Normand, G.M. Anderson, K. Sykora, K. Lam, C.M. Bell, P.E. Lee, H.D. Fischer, N. Herrmann, J.H. Gurwitz, P.A. Rochon.

Drafting of the article: S.S. Gill, S.E. Bronskill.

Critical revision of the article for important intellectual content: S.S. Gill, S.E. Bronskill, G.M. Anderson, K. Sykora, K. Lam, C.M. Bell, P.E. Lee, H.D. Fischer, N. Herrmann, J.H. Gurwitz, P.A. Rochon.

Final approval of the article: S.S. Gill, C.M. Bell, N. Herrmann, J.H. Gurwitz, P.A. Rochon.

Statistical expertise: S.S. Gill, S.E. Bronskill, S.-L.T. Normand, K. Sykora, K. Lam.

Administrative, technical, or logistic support: K. Sykora, K. Lam, H.D. Fischer.

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