Frailty Risks of Prescription Analgesics and Sedatives across Frailty Models: the Health and Retirement Study

Introduction Limited evidence for incident frailty risks associated with prescription analgesics and sedatives in older (>= 65 years) community-living adults prompted a more comprehensive investigation. Methods We used data from older Health and Retirement Study respondents and three frailty models (frailty index, functional domain, frailty phenotype with 8803, 10,470, and 6850 non-frail individuals, respectively) and estimated sub-hazard ratios of regular prescription drug use (co-use, analgesic use, and sedative use), by frailty model. We addressed confounding with covariate adjustment and propensity score matching approaches. Results The baseline prevalence of analgesic and sedative co-use, analgesic use, and sedative use among non-frail respondents was 1.8%, 12.8%, and 4.7% for the frailty index model, 4.2%, 16.2%, and 5.3% for the functional domain model, and 4.3%, 15.4%, and 6.1% for the frailty phenotype model, respectively. Cumulative frailty incidence over 10 years was 39.3%, 36.1%, and 14.2% for frailty index, functional domain, and frailty phenotype models, respectively; covariate-adjusted sub-hazard ratio estimates were 2.00 (1.63-2.45), 1.83 (1.57-2.13), and 1.68 (1.21-2.33) for co-use; 1.72 (1.56-1.89), 1.38 (1.27-1.51), and 1.51 (1.27-1.79) for analgesic use; and 1.46 (1.24-1.72), 1.25 (1.07-1.46), and 1.31 (0.97-1.76) for sedative use. Frailty risk ranking (co-use > analgesic use > sedative use) persisted across all model sensitivity analyses. Discussion Consistently significant frailty risk estimates of regular prescription analgesic and sedative co-use and of prescription analgesic use support existing clinical, public health, and regulatory guidance on opioid and benzodiazepine co-prescription, on opioid prescription, and on NSAID prescription. Frailty phenotype measurement administration limited power to detect significant frailty risks. Research into specific pharmaceutical exposures and comparison of results across cohorts will be required to contribute to the deprescribing evidence base.