Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study
BMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e977 (Published 23 February 2012) Cite this as: BMJ 2012;344:e977
- K F Huybrechts, instructor in medicine1,
- T Gerhard, assistant professor2,
- S Crystal, board of governors professor2,
- M Olfson, professor of clinical psychiatry3,
- J Avorn, professor of medicine1,
- R Levin, programmer1,
- J A Lucas, assistant research professor4,
- S Schneeweiss, associate professor of medicine1
- 1Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston 02120, MA, United States
- 2Ernest Mario School of Pharmacy, Rutgers University, New Brunswick, NJ 08901
- 3Columbia University, New York, NY 10032
- 4Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ 08901
- Correspondence to: K F Huybrechts khuybrechts{at}partners.org
- Accepted 29 December 2011
Abstract
Objective To assess risks of mortality associated with use of individual antipsychotic drugs in elderly residents in nursing homes.
Design Population based cohort study with linked data from Medicaid, Medicare, the Minimum Data Set, the National Death Index, and a national assessment of nursing home quality.
Setting Nursing homes in the United States.
Participants 75 445 new users of antipsychotic drugs (haloperidol, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone). All participants were aged ≥65, were eligible for Medicaid, and lived in a nursing home in 2001-5.
Main outcome measures Cox proportional hazards models were used to compare 180 day risks of all cause and cause specific mortality by individual drug, with propensity score adjustment to control for potential confounders.
Results Compared with risperidone, users of haloperidol had an increased risk of mortality (hazard ratio 2.07, 95% confidence interval 1.89 to 2.26) and users of quetiapine a decreased risk (0.81, 0.75 to 0.88). The effects were strongest shortly after the start of treatment, remained after adjustment for dose, and were seen for all causes of death examined. No clinically meaningful differences were observed for the other drugs. There was no evidence that the effect measure modification in those with dementia or behavioural disturbances. There was a dose-response relation for all drugs except quetiapine.
Conclusions Though these findings cannot prove causality, and we cannot rule out the possibility of residual confounding, they provide more evidence of the risk of using these drugs in older patients, reinforcing the concept that they should not be used in the absence of clear need. The data suggest that the risk of mortality with these drugs is generally increased with higher doses and seems to be highest for haloperidol and least for quetiapine.
Footnotes
Contributors: All authors were responsible for study concept and design. SC and SS acquired the data, which were analysed and interpreted by all authors. KFH drafted the manuscript, which was critically revised for important intellectual content by all authors. KFH, TG, RL, and SS did the statistical analysis. SC, JA, and SS gave administrative, technical, or material support. SS was the study supervisor, and KFH is guarantor.
Funding: This study was supported by AHRQ/FDA Award HS017918 and AHRQ Award HS016097. KFH and SS were partially funded by National Institute of Mental Health R01-MH078708. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.
Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Ethical approval: This study was approved by the Institutional Review Board of the Brigham and Women’s Hospital, the Partners Human Research Committee.
Data sharing: No additional data available.
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