Polypharmacy and mortality in hospitalized older adults: Systematic review with exploratory meta-analysis

Polypharmacy is common in hospitalized older adults, but its independent relationship with mortality remains uncertain. We conducted a PRISMA 2020 systematic review, prospectively registered in PROSPERO (CRD420261398125), of observational studies assessing polypharmacy, excessive polypharmacy, or potentially inappropriate medication and mortality in hospitalized older patients. PubMed/MEDLINE, Scopus, Web of Science, Embase, and LILACS were searched. Of 134 records, seven studies entered the qualitative synthesis and three the exploratory meta-analysis. The pooled estimate showed substantial statistical uncertainty and high heterogeneity (OR=2.23; 95%CI: 0.77-6.43; I²=87.2%). After excluding the COVID-19 study, the magnitude of the association decreased (OR=1.20; 95%CI: 0.77-1.88; I²=11.7%). Polypharmacy appears to function mainly as a marker of multimorbidity, frailty, and clinical severity. These findings are hypothesis-generating and do not support causal inference. Excessive polypharmacy and potentially inappropriate prescribing may discriminate risk better than the isolated five-medication threshold.