Drugs & Aging · Oct 26, 2026

Comparative Impact of Anticholinergic Exposure, Potentially Inappropriate Medications, and Polypharmacy on Clinical Outcomes: A Nationwide Claims Database Study in Japan

By Uematsu T, Nojiri S, Fujikawa H et al.

BACKGROUND: In Japan, polypharmacy has become a major clinical issue as the population continues to age. Although anticholinergic drugs and potentially inappropriate medications (PIMs) have been associated with adverse outcomes, the utility of and differences among medication-related indicators, including the Japanese Anticholinergic Risk Scale, remain unclear. OBJECTIVES: This study aimed to compare the associations between different medication-related indicators and major clinical outcomes. METHODS: Using a large-scale administrative claims database, we conducted a population-based matched case-control study to evaluate the associations between medication-related indicators, including the number of anticholinergic drugs, total anticholinergic burden, number of potentially inappropriate medications, and total number of medications, and specific clinical outcomes, as well as their associations across predefined categories. RESULTS: The number of anticholinergic drugs and total anticholinergic burden were significantly associated with hip fracture and dementia. In contrast, for constipation and urinary retention, the total number of medications showed associations comparable to those of anticholinergic exposure. Overall, the strengths of the associations for the number of anticholinergic drugs and total anticholinergic burden were broadly similar. Comparisons of the number of anticholinergic drugs, total number of potentially inappropriate medications, and total number of medications revealed stronger associations of anticholinergic drugs and PIMs with hip fracture and dementia, whereas all three indexes showed comparable associations with constipation and urinary retention. CONCLUSIONS: These findings suggest that comprehensive exposure assessments that account for disease characteristics and temporal factors are crucial for appropriately evaluating medication-related risks.

doi.org/10.1007/s40266-026-01344-3PubMed 42931882Populations