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Antipsychotic Drug Use and Mortality in Older Adults with Dementia
Abstract
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.
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“A similar black box warning for conventional antipsychotics, based on two observational studies that showed increased risk of mortality in older adults using conventional versus atypical antipsychotics, was announced in 2008.117 118 119”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [118]
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“As a result, it announced a black box warning for the use of atypical antipsychotics for behavioral and psychological symptoms of dementia.”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [118]
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“In 2005, the FDA announced that, based on a re-analysis of 17 placebo controlled trials (several of which were unpublished), atypical antipsychotics were associated with a 1.7-fold increase in mortality compared with placebo.117 118”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [118]
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“A meta-analysis found an odds ratio for mortality with these drugs of 1.54 (1.06 to 2.23; Z=2.28; P=0.02), with pooled events of 3.5% mortality for the drug versus 2.3% for placebo.”
From Assessment and management of behavioral and psychological symptoms of dementia (2015) · cites this paper as [118]
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“Some studies have shown that nonpharmacological treatments pose fewer side effects, which render them as safer options [20].”
From Nonpharmacological Interventions to Reduce Behavioral and Psychological Symptoms of Dementia: A Systematic Review (2015) · cites this paper as [20]
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Metadata
- Authors
- Gill, S. S., Bronskill, S. E., Normand, S.-L. T., Anderson, G. M., Sykora, K., Lam, K., Bell, C. M., Lee, P. E., Fischer, H. D., Herrmann, N., Gurwitz, J. H., & Rochon, P. A.
- Affiliations
- Harvard University (US)
- 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.
- ORCID
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2007-06-05
- Volume
- 146
- Issue
- 11
- Pages
- 775-786
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W2144855317
- Cited by
- 624
- References
- 66
- Citations by year
- 2026: 12 · 2025: 24 · 2024: 17 · 2023: 22 · 2022: 30 · 2021: 18 · 2020: 27 · 2019: 31 · 2018: 38 · 2017: 36 · 2016: 45 · 2015: 42 · 2014: 30 · 2013: 37 · 2012: 35
- FWCI
- 26.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- antipsychotic drugs, atypical antipsychotics, typical antipsychotics, dementia, all-cause mortality, older adults, behavioral and psychological symptoms of dementia, long-term care, community-dwelling older adults, drug safety
- MeSH terms
- Aged, Aged, 80 and over, Dementia, Female, Humans, Male, Ontario, Sensitivity and Specificity, Time Factors, Antipsychotic Agents, Matched-Pair Analysis, Risk Assessment
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