Clinician Article

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

  • Huybrechts KF
  • Gerhard T
  • Crystal S
  • Olfson M
  • Avorn J
  • Levin R, et al.
BMJ. 2012 Feb 23;344:e977. doi: 10.1136/bmj.e977. (Original)
PMID: 22362541
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  • Psychiatry
    Relevance - 7/7
    Newsworthiness - 5/7
  • Geriatrics
    Relevance - 7/7
    Newsworthiness - 4/7


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.

Clinical Comments


I find this type of research very disturbing. It provides more `proof` that haloperidol is more toxic (higher mortality) than risperidone in nursing home patients based on a review of a large database, except that the patients in the database who got haloperidol were more likely to have CHF, were functionally more dependent, were less likely to be on an antidepressant or an acetylcholinesterase inhibitor, and more likely to be on sedative hypnotics. Stating that nursing home patients in the study who receive haloperidol are likely to be sicker and to be medicated differently in many respects BECAUSE they are sicker than patients in the study who receive risperidone would be more accurate.


Reinforces the known harms of both typical and atypical antipsychotics in older institutionalized patients. We also know these agents are of limited efficacy. What is needed is data on why the drugs continue to be prescribed and how this practice can be altered.


Despite warnings since 2004 about an increased mortality risk associated with the use of typical and atypical antipsychotics in patients with dementia, they are still frequently prescribed. This article provides additional corroboration of the increased mortality risk and shows a dose-response relationship for some, but not all, of the drugs studied. A direct comparison of the relative risks associated with individual agents is new and clinically important information. The paper is methodologically strong, and the risks are based on the NEW use of the antipsychotic. The reason(s) for prescription are unknown, and it is interesting that fewer than 2/3 of the patients had a diagnosis of dementia, and only about 1/4 had non-aggressive behavioral problems, which begs the question, Why were these medications prescribed in the first place? A review should emphasize how poorly behavioral problems in dementia are evaluated. There is a good accompanying editorial: BMJ 2012;344:e1093.

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