Mediators of First- Versus Second-generation Antipsychotic-related Mortality in Older Adults
Year: 2015
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Observational studies of older adults showed higher mortality for first-generation antipsychotics than their second- generation counterparts, which led to US Food and Drug Administration warnings, but the actual mechanisms involved remain unclear. METHODS: A cohort of 9,060 initiators of first-generation antipsychotics and 17,137 of second-generation antipsychotics enrolled in New Jersey and Pennsylvania Medicare were followed for 180 days. Medical events were assessed using diagnostic and procedure codes on inpatient billing claims. For the individual and joint set of medical events (mediators), we estimated the total, direct, and indirect effects of antipsychotic type (first versus second generation) on mortality on the risk ratio scale and the proportion mediated on the risk difference scale, obtaining 95% confidence intervals through bootstrapping. We performed bias analyses for false-negative mediator misclassification in claims data, with sensitivity ranging from 0.25 to 0.75. RESULTS: There were 3,199 deaths (outcomes), 862 cardiovascular events, 675 infectious events, and 491 hip fractures (potential mediators). Mortality was higher for first- than second-generation antipsychotic initiators (adjusted risk ratio: 1.14; 95% confidence interval: 1.06, 1.22). In naïve analyses, that ignored potential misclassification, less than 4% of this difference was explained by any particular medical event. In bias analyses, the proportion mediated ranged from 6% to 16% for stroke, 3% to 9% for ventricular arrhythmia, 3% to 11% for myocardial infarction, 0% venous thromboembolism, 3% to 9% for pneumonia, 0% to 1% for other bacterial infection, and 1% to 3% for hip fracture. CONCLUSIONS: Acute cardiovascular events and pneumonia may explain part of the mortality difference between first- and second-generation antipsychotic initiators in this analysis.
Source: Epidemiology
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Risk factors for asymptomatic diverticulosis, Intestinal Microbiota, Diet and Risk of Colorectal Adenomas, Training Program in Psychiatric Genetics and Translational Research, NC Colorectal Cancer Care Outcomes Research Study, Theory and methods for sufficient cause interactions, Implementing Systemic Interventions to Close the Discovery-Delivery Gap, G5438098262, INFLAMMATION, OBESITY AND RISK OF COLORECTAL ADENOMAS, Massachusetts Alzheimer's Disease Research Center, Propensity Scores and Preventive Drug Use in the Elderly, Center for Gastrointestinal Biology and Disease
OpenAlex ID: W560053054