Haloperidol Doubles Risk of Death in Nursing Home Residents

Abstract

C with risperidone, haloperidol appeared to double the risk of death among elderly nursing home patients, while quetiapine was associated with a 20% decreased risk and some other antipsychotics appeared uniformly safe, Krista F. Huybrechts, Ph.D., and her colleagues wrote in BMJ (2012;344:e977). “The evidence accumulated so far implies that use of haloperidol in this vulnerable population cannot be justified because of the excess harm,” wrote Dr. Huybrechts of Brigham and Women’s Hospital, Boston. “If the clinician faces a situation in which the use of these drugs seem inevitable, our findings underscore the importance of always prescribing the lowest possible dose and of closely monitoring patients, especially shortly after the start of treatment.” Dr. Huybrechts and her coauthors reviewed medication and mortality data on 75,445 nursing home residents who were aged 65 or older and new users of antipsychotic medications from 2001– 2005. About 60% of the group had some form of dementia. Other psychiatric diagnoses included depression, anxiety, delirium, and psychotic disorders. The study examined the use of haloperidol, aripiprazole, olanzapine, risperidone, and ziprasidone. Other medications, like thioridazine and chlorpromazine, were excluded from the analysis because they were infrequently prescribed in the group. There were 6,598 deaths (9% of the study cohort) during the first 180 days. In a regression analysis, those taking haloperidol were twice as likely to die from any cause as those taking risperidone. The risk was strongest in the first 40 days of treatment (hazard ratio 2.34) and declined thereafter. Conversely, patients taking quetiapine were significantly less likely to die (HR, 0.81), and that risk remained fairly constant throughout the 180-day study period. No significant or clinically meaningful mortality trend was associated with the use of aripiprazole, olanzapine, risperidone, or ziprasidone. The investigators found no tie between the drug administered and the cause of death. “The increased risk of death with haloperidol and the decreased risk with quetiapine were observed for all causes examined,” they said. Every drug except quetiapine showed a dose-response relationship with allcause mortality. The relationship was most pronounced for haloperidol, with an 84% increased risk in those taking a high dose, and a 40% increased risk for those taking a medium dose, compared with those taking a low dose. The study emphasizes the need to use alternative behavioral management tools for as long as possible in nursing home patients, the authors said. “Guidelines universally agree that the first-line treatment for behavioral and psychological symptoms in dementia should be non–drug based, [but also] recommend the careful use of antipsychotics in the treatment of agitation, aggression, or psychosis that fails to respond to other measures and that reaches various severity thresholds, typically severe distress or serious risk to self or others,” Dr. Jenny McCleery said in an accompanying editorial (BMJ 2012;344:e1093). She is a consulting psychiatrist for the Oxford (England) Health National Health Systems Foundation Trust. Despite recommendations to limit the drugs’ use, however, antipsychotics are still widely prescribed for elderly patients with dementia or those who are institutionalized. “Few clinical problems place doctors in as tangled a web of clinical evidence, social policy, and ethical concerns as how to manage behavioral problems in patients with dementia,” Dr. McCleery wrote. Studies hint that doctors feel pressured to prescribe anything that might help and that they believe alternative therapies are hard to implement, she added. “The Food and Drug Administration, and the Agency for Healthcare Research and Quality funded the study. None of the authors reported any financial conflict of interest. Dr. McCleery said she has acted as a local investigator for Eli Lilly. CfA