Among 4,110 community-dwelling Colombian adults aged 60+ followed for a mean of 79 months, polypharmacy (5–9 concurrent medications) raised all-cause mortality risk by 17% (HR 1.17; 95% CI 1.02–1.31), while excessive polypharmacy (≥10 medications) nearly doubled it (HR 1.82; 95% CI 1.34–2.47). These hazard ratios held after adjusting for multimorbidity, functional dependency, and sociodemographic factors — with 1,092 deaths recorded (26.6% of the cohort). The non-linear jump at the 10-drug threshold is particularly striking.
This preprint — not yet peer-reviewed — adds important longitudinal data from Latin America, a region historically underrepresented in aging pharmacology research. The magnitude of risk at the excessive polypharmacy threshold aligns with European and North American cohort studies, suggesting the danger of high medication burden transcends healthcare system type. Crucially, the authors adjusted for multimorbidity, partially addressing the core confounding problem in polypharmacy research: sicker patients take more drugs and die more often regardless. Yet residual confounding remains a legitimate concern, and causal direction cannot be established from observational data alone. The ~79-month follow-up is a genuine strength, extending beyond most comparable studies. Practically, these findings reinforce structured deprescribing as a priority intervention — particularly relevant in resource-constrained systems where medication reviews are inconsistent. For clinicians and older adults alike, the 10-drug threshold emerges as a meaningful clinical alarm point warranting urgent medication reconciliation.