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Cited by 366Schizophrenia research and treatmentPharmaceutical Practices and Patient OutcomesDementia and Cognitive Impairment Research

Risk of death associated with the use of conventional versus atypical antipsychotic drugs among elderly patients

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Schneeweiss, S., Setoguchi, S., Brookhart, A., Dormuth, C., Wang, P. S.·2007·Canadian Medical Association Journal
DOI 10.1503/cmaj.061250PMC PMC1800321
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Abstract

BACKGROUND: Public health advisories have warned that the use of atypical antipsychotic medications increases the risk of death among elderly patients. We assessed the short-term mortality in a population-based cohort of elderly people in British Columbia who were prescribed conventional and atypical antipsychotic medications. METHODS: We used linked health care utilization data of all BC residents to identify a cohort of people aged 65 years and older who began taking antipsychotic medications between January 1996 and December 2004 and were free of cancer. We compared the 180-day all-cause mortality between residents taking conventional antipsychotic medications and those taking atypical antipsychotic medications. RESULTS: Of 37 241 elderly people in the study cohort, 12 882 were prescribed a conventional antipsychotic medication and 24 359 an atypical formulation. Within the first 180 days of use, 1822 patients (14.1%) in the conventional drug group died, compared with 2337 (9.6%) in the atypical drug group (mortality ratio 1.47, 95% confidence interval [CI] 1.39-1.56). Multivariable adjustment resulted in a 180-day mortality ratio of 1.32 (1.23-1.42). In comparison with risperidone, haloperidol was associated with the greatest increase in mortality (mortality ratio 2.14, 95% CI 1.86-2.45) and loxapine the lowest (mortality ratio 1.29, 95% CI 1.19-1.40). The greatest increase in mortality occurred among people taking higher (above median) doses of conventional antipsychotic medications (mortality ratio 1.67, 95% CI 1.50-1.86) and during the first 40 days after the start of drug therapy (mortality ratio 1.60, 95% CI 1.42-1.80). Results were confirmed in propensity score analyses and instrumental variable estimation, minimizing residual confounding. INTERPRETATION: Among elderly patients, the risk of death associated with conventional antipsychotic medications is comparable to and possibly greater than the risk of death associated with atypical antipsychotic medications. Until further evidence is available, physicians should consider all antipsychotic medications to be equally risky in elderly patients.

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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.

    “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 [119]

    The Results report higher 180-day mortality among elderly users of conventional versus atypical antipsychotics, and the Interpretation cites a similar earlier observational finding. The paper does not establish that a warning for conventional antipsychotics was announced in 2008; its Interpretation says the advisories at the time warned only about atypical drugs and recommends extending them. (LLM, conf=0.87)

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Authors
Schneeweiss, S., Setoguchi, S., Brookhart, A., Dormuth, C., & Wang, P. S.
Affiliations
  • Brigham and Women's Hospital (US)
  • University of British Columbia (CA)
  • National Institutes of Health (US)
ORCID
Venue
Canadian Medical Association Journal
Publisher
CMA Joule Inc.
Published
2007-02-07
Volume
176
Issue
5
Pages
627-632
ISSN
  • 0820-3946 (ISSN-L)
  • 1488-2329
DOI
10.1503/cmaj.061250
PMC
PMC1800321
OpenAlex
W2140295766
Cited by
366
References
0
Citations by year
2026: 4 · 2025: 9 · 2024: 7 · 2023: 5 · 2022: 12 · 2021: 8 · 2020: 21 · 2019: 12 · 2018: 16 · 2017: 20 · 2016: 26 · 2015: 22 · 2014: 24 · 2013: 32 · 2012: 22
FWCI
18.19
Type
journal article
Language
en
Open access
Locations
  • Canadian Medical Association Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Brigham and Women's Hospital
  • U.S. Public Health Service (29020050016I)
  • National Institute on Aging (R01AG021950)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
typical antipsychotics, elderly patients, all-cause mortality, drug safety, haloperidol, risperidone, loxapine, dose-response relationship, propensity score analysis, instrumental variable estimation
MeSH terms
Aged, British Columbia, Female, Humans, Male, Mortality, Risk Factors, Antipsychotic Agents, Multivariate Analysis, Proportional Hazards Models

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