Global prevalence, trends, and dose-response associations of polypharmacy in older adults

Polypharmacy is common in older adults with comorbidities. This study aims to estimate its global prevalence, temporal trends, and dose-response associations with adverse health outcomes. PubMed, Embase, The Cochrane Library, Web of Science, and Scopus were searched from inception to June 30, 2025. Random-effects meta-analyses were used to pool prevalence estimates of polypharmacy based on mixed thresholds and relative risks. Study quality was assessed using Hoy's method. Hazard ratios (HRs) from individual studies were synthesized using random-effects dose-response meta-analysis in studies that provided sufficient quantitative exposure information. A total of 545 studies, providing 565 prevalence estimates, were included, comprising 16 620 414 older adults from 56 countries worldwide. The pooled global prevalence of polypharmacy was 50.4% (95% confidence interval [CI]: 48.2%-52.7%; 95% prediction interval: 6.8%-93.5%). It demonstrated a significant increasing temporal trend in polypharmacy prevalence over calendar years. Compared with non-polypharmacy, polypharmacy was associated with a significantly higher risk of multiple adverse outcomes. Dose-response meta-analyses showed a monotonic increase in risk with each additional medication for mortality (HR: 1.05, 95% CI: 1.03-1.06, p < .001), emergency (HR: 1.02, 95% CI: 1.02-1.03, p < .001), and hospital admission (HR: 1.04, 95% CI: 1.02-1.07, p < .001). Outcome-specific thresholds ranged from 4.55 to 5.46 medications. A pooled estimate of approximately five medications was obtained as a descriptive summary across outcomes. Polypharmacy affects approximately half of older adults worldwide and has increased steadily over time. It is associated with an increased risk of multiple adverse health outcomes, with risks increasing progressively as medication burden rises.