Abstract and Introduction
Abstract
Objectives: To compare the risk of major medical events in nursing home residents newly initiated on conventional or atypical antipsychotic medications (APMs).
Design: Cohort study, using linked Medicaid, Medicare, Minimum Data Set, and Online Survey Certification and Reporting data. Propensity score-adjusted proportional hazards models were used to compare risks for medical events at a class and individual drug level.
Setting: Nursing homes in 45 U.S. states.
Participants: Eighty-three thousand nine hundred fifty-nine Medicaid-eligible residents aged 65 and older who initiated APM treatment after nursing home admission in 2001 to 2005.
Measurements: Hospitalization for myocardial infarction, cerebrovascular events, serious bacterial infections, and hip fracture within 180 days of treatment initiation.
Results: Risks of bacterial infections (hazard ratio (HR) = 1.25, 95% confidence interval (CI) = 1.05–1.49) and possibly myocardial infarction (HR = 1.23, 95% CI = 0.81–1.86) and hip fracture (HR = 1.29, 95% CI = 0.95–1.76) were higher, and risks of cerebrovascular events (HR = 0.82, 95% CI = 0.65–1.02) were lower in participants initiating conventional APMs than in those initiating atypical APMs. Little variation existed between individual atypical APMs, except for a somewhat lower risk of cerebrovascular events with olanzapine (HR = 0.91, 95% CI = 0.81–1.02) and quetiapine (HR = 0.89, 95% CI = 0.79–1.02) and a lower risk of bacterial infections (HR = 0.83, 95% CI = 0.73–0.94) and possibly a higher risk of hip fracture (HR = 1.17, 95% CI = 0.96–1.43) with quetiapine than with risperidone. Dose-response relationships were observed for all events (HR = 1.12, 95% CI = 1.05–1.19 for high vs low dose for all events combined).
Conclusion: These associations underscore the importance of carefully selecting the specific APM and dose and monitoring their safety, especially in nursing home residents who have an array of medical illnesses and are undergoing complex medication regimens.
Introduction
Antipsychotic medication (APM) use is widespread in nursing homes (NHs), especially in residents with behavioral disturbances. Up to one-third of all NH residents receive APMs, mostly for the treatment of dementia-related behavioral disturbances, but serious safety concerns surround use of APMs in older adults with dementia-related psychoses. Based on randomized trials, the Food and Drug Administration (FDA) issued warnings of risks of stroke and transient ischemic events for risperidone (2003) followed by olanzapine and aripiprazole (2004). In 2005, the FDA issued warnings of excess mortality associated with the use of atypical APMs in older adults with dementia. Moreover, a National Institutes of Health-sponsored clinical trial concluded that the adverse effects of atypical APMs offset their efficacy advantage in individuals with Alzheimer's disease and that worsening of cognitive function is an additional risk of treatment with atypical APMs. In June 2008, the FDA requested a similar boxed warning for conventional APMs based on nonrandomized studies that used healthcare utilization databases. The proposed mechanisms for the higher mortality remain speculative and include metabolic dysregulation; cardiac conduction disturbances; changes in blood pressure or heart rate, which may exacerbate preexisting heart failure; and sedation leading to aspiration with secondary pneumonia. Gait and movement disorders, confusion, delirium, excessive sedation, and orthostatic hypotension have also been associated with APM use and are well-established risk factors for falls and hip fractures.
An important next step in assessing the comparative safety of APMs is to examine the risk of these potential mediating cardiac and cerebrovascular events, infections, and hip fractures and to examine the extent to which these risks differ between classes and between individual APMs. These questions were addressed in a cohort of NH residents, who represent the most vulnerable and most widely treated segment of the elderly population