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. 2012 Feb 23:344:e977.
doi: 10.1136/bmj.e977.

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study

K F Huybrechts  1 , T Gerhard, S Crystal, M Olfson, J Avorn, R Levin, J A Lucas, S Schneeweiss
Affiliations

Differential risk of death in older residents in nursing homes prescribed specific antipsychotic drugs: population based cohort study

K F Huybrechts et al. BMJ. .

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.

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Conflict of interest statement

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.

Figures

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Fig 1 Assembly of study cohort of patients in nursing homes starting treatment with antipsychotic drugs (ICD-9=international classification of diseases, ninth revision; MDS=Minimum Data Set; OSCAR=Online Survey Certification and Reporting)
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Fig 2 Adjusted Kaplan-Meier plots for death from causes other than cancer. Each participant is weighed by inverse of his or her probability for treatment as estimated in multivariate propensity score analysis
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Fig 3 Hazard ratios (adjusted for propensity score) for death from causes other than cancer by dose of various antipsychotic drugs compared with similar dose of risperidone (restricted to users of tablets or caplets). Results for aripiprazole and ziprasidone not presented because of small numbers of events in some dose groups
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Fig 4 Hazard ratios (adjusted propensity score) for death from causes other than cancer by dose of various antipsychotic drugs with low dose group of each drug as reference. Results for aripiprazole and ziprasidone not presented because of small numbers of events in some dose groups
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