Frailty Status and Medication Use Among U.S. Older Adults: Evidence From NHANES , 1999–2020

BACKGROUND: Frailty and polypharmacy commonly coexist among older adults, yet population-level evidence on how the extent and therapeutic composition of medication use evolve across frailty stages remains limited. METHODS: We analyzed nationally representative data from the U.S. National Health and Nutrition Examination Survey spanning 1999 through March 2020. Of 14,962 community-dwelling adults aged ≥ 65 years, 12,766 had sufficient data to construct a frailty index (FI). Frailty was categorized as robust (FI < 0.25), mildly frail (FI 0.25-0.34), or moderate to severely frail (FI ≥ 0.35). Outcomes included the mean number of prescription medications overall and by therapeutic class. Temporal trends were evaluated across frailty groups accounting for the complex survey design. RESULTS: Medication use increased across all frailty groups from 1999-2000 to 2017-2020. The mean number of medications increased from 2.0 to 2.9 among robust individuals (p for trend < 0.001), from 3.9 to 5.5 among mildly frail individuals (p < 0.001), and from 6.0 to 7.8 among those with moderate to severe frailty (p = 0.001). Although cardiovascular agents consistently constituted the largest share of polypharmacy, their use remained stable. In contrast, metabolic and CNS/psychotherapeutic agents drove longitudinal increases in medication burden, with metabolic agents increasing across all frailty strata and CNS/psychotherapeutic agents increasing primarily among adults with moderate to severe frailty (p < 0.001). In 2017-2020, hyperpolypharmacy (≥ 10 medications) composition varied markedly by frailty status. Robust older adults predominantly used CNS/psychotherapeutic and topical agents, whereas frail adults primarily used cardiovascular and metabolic agents. CONCLUSION: Medication use among U.S. older adults increased substantially over two decades, with both the magnitude and composition of medication use pattern varying systematically by frailty status. These findings characterize the population-level landscape of frailty-stratified medication burden and provide clinical context for further research and efforts aimed at optimizing medication use across the frailty spectrum in older adults.