Polypharmacy in the Geriatric Population: A Comprehensive Systematic Review of Epidemiology, Pathophysiology, Clinical Consequences, and Pharmacotherapy Optimization Strategies

Population aging has become a major demographic and public health challenge worldwide. Increased life expectancy and advances in healthcare have led to a growing number of older adults living with multiple chronic diseases. Consequently, multimorbidity and polypharmacy have become increasingly common in geriatric practice. Polypharmacy is commonly defined as the regular use of five or more medications, while excessive polypharmacy refers to the use of ten or more drugs. Modern geriatric medicine emphasizes that the appropriateness of treatment is more important than the number of medications alone. Therefore, a distinction should be made between appropriate and inappropriate polypharmacy. Appropriate polypharmacy refers to evidence-based pharmacotherapy in which multiple medications are clinically justified and optimized to improve patient outcomes. Inappropriate polypharmacy occurs when medications without clear indications are prescribed, when therapeutic duplication exists, or when treatment risks outweigh benefits. Older adults are particularly vulnerable to adverse drug reactions because of age-related physiological changes, frailty, cognitive impairment, and multiple comorbidities. An important mechanism contributing to inappropriate polypharmacy is the prescribing cascade, in which adverse drug reactions are misinterpreted as new medical conditions, leading to additional prescriptions. This process increases the risk of drug–drug interactions, hospitalization, functional decline, and reduced quality of life. Symptoms such as dizziness, fatigue, falls, constipation, or cognitive impairment may often result from medication-related toxicity rather than normal aging. This systematic review summarizes the epidemiology, mechanisms, clinical consequences, and evidence-based strategies for optimizing pharmacotherapy in older adults, including medication review, deprescribing, interdisciplinary collaboration, and individualized patient-centered care.