The Burden of Inappropriate Polypharmacy: Approaches to Improve Medication Safety

Polypharmacy, defined as the concurrent use of multiple medications, has become an increasingly common feature of modern healthcare, particularly among aging populations with complex multimorbidity. While the use of multiple drugs may be clinically justified in many circumstances, the growing prevalence of medication regimens that expose patients to unnecessary risk has raised significant clinical, economic, and regulatory concerns. Adverse drug events, prescribing cascades, drug–drug interactions, and the underrecognized contribution of herb-drug interactions collectively underscore the challenges associated with contemporary pharmacotherapy. This chapter situates polypharmacy within the broader context of healthcare system pressures and evolving therapeutic paradigms, highlighting the conditions under which medication use transitions from rational complexity to avoidable harm. Established clinical practices, including pharmacotherapy vigilance, interprofessional medication review, and deprescribing frameworks, are discussed alongside emerging pharmaceutical strategies designed to streamline treatment regimens. In parallel, advances in artificial intelligence-supported clinical decision systems are considered for their potential to enhance the individualized risk assessment and support safer medication management. By integrating clinical stewardship with pharmaceutical and technological innovation, the chapter provides a cohesive perspective on addressing medication-related complexity in chronic disease management, with particular attention to minimizing preventable harm while preserving the therapeutic efficacy.