Polypharmacy and Deprescribing in Multimorbid Patients: Real-World Outcomes, Safety, and Prescribing Policy

Multimorbidity — the co-occurrence of two or more chronic conditions in a single patient — is now the norm rather than the exception in most healthcare systems. It is estimated that over half of adults aged 65 and above live with multimorbidity, and prevalence continues to rise with ageing populations and improved survival from previously fatal conditions. Because clinical guidelines are predominantly designed around single-disease management, multimorbid patients are frequently managed by accumulating recommendations across conditions, resulting in polypharmacy — commonly defined as the concurrent use of five or more medications, with excessive polypharmacy referring to ten or more.Polypharmacy is not inherently inappropriate: in many multimorbid patients, multiple medications are clinically justified. The challenge lies in distinguishing appropriate from inappropriate polypharmacy. Potentially inappropriate prescribing (PIP) — including medications that carry a risk disproportionate to their benefit in specific populations, prescribing cascades in which drug side effects are treated with further drugs, and omission of clinically indicated therapies — contributes substantially to adverse drug reactions (ADRs), drug–drug interactions (DDIs), drug–disease interactions, medication non-adherence, hospitalisation, falls, and functional decline. Tools such as the Beers Criteria, STOPP/START criteria, the Medication Appropriateness Index (MAI), and the FORTA classification provide structured frameworks for identifying and addressing PIP, though their uptake and comparative effectiveness in routine clinical practice remain incompletely characterised.Deprescribing — the systematic, patient-centred process of tapering, withdrawing, or substituting medications where the potential for harm outweighs benefit — has gained substantial momentum as a clinical and policy priority. Despite a growing body of evidence supporting deprescribing in specific drug classes (proton pump inhibitors, antihypertensives, antipsychotics, benzodiazepines, and statins in the context of limited life expectancy), the evidence base for deprescribing outcomes across broader multimorbid populations remains fragmented. Barriers to deprescribing are well described and include prescriber reluctance, patient and caregiver expectations, fear of symptom recurrence, lack of standardised protocols, and insufficient time in clinical encounters for structured medication review. Pharmacist-led and multidisciplinary medication review programmes have shown promise but have yet to be systematically integrated into prescribing policy at scale.Real-world evidence (RWE) — drawn from electronic health records (EHRs), national registries, claims databases, and pharmacovigilance systems — is critical for understanding polypharmacy and deprescribing outcomes beyond the controlled conditions of clinical trials. Multimorbid patients are routinely excluded from randomised controlled trials, meaning that trial-derived evidence frequently does not reflect their clinical reality. Observational studies, pragmatic trials, and prospective cohort analyses represent the primary evidence base for this population, alongside patient-reported outcome measures (PROMs) capturing quality of life, symptom burden, and treatment satisfaction. Pharmacoepidemiological approaches — including active surveillance, disproportionality analyses, and comparative effectiveness research — are essential for characterising the safety profile of complex medication regimens in routine care. While real-world evidence from pharmacovigilance systems is welcome, isolated retrospective data-mining studies using databases such as FAERS are not encouraged.At the policy level, prescribing in multimorbid patients represents a significant patient safety, economic, and public health challenge. Medication-related harms account for a substantial proportion of preventable hospital admissions globally, with polypharmacy-related ADRs disproportionately represented. Health technology assessment (HTA) frameworks and quality indicators for prescribing appropriateness are evolving but inconsistently applied across health systems. Digital decision-support tools, including clinical decision support systems (CDSS) and AI-assisted prescribing aids embedded in EHRs, offer scalable approaches to identifying and reducing potentially inappropriate prescribing, though their real-world implementation and impact on patient outcomes require rigorous evaluation.This Research Topic invites original research, systematic reviews, meta-analyses, narrative reviews, and policy analyses that advance the evidence base for polypharmacy management and deprescribing in multimorbid patients. Contributions representing diverse healthcare settings and regions, including low- and middle-income countries, are particularly welcome, to ensure the evidence base reflects the global burden of multimorbidity. The Topic focuses on:• Prevalence, patterns, and determinants of polypharmacy and potentially inappropriate prescribing across healthcare settings and patient populations• Real-world outcomes of polypharmacy, including ADRs, drug–drug interactions, hospitalisations, falls, cognitive impairment, and mortality• Effectiveness and safety of deprescribing interventions across specific drug classes and patient populations• Barriers and facilitators to deprescribing in clinical practice, including patient, prescriber, and system-level factors• Pharmacist-led, multidisciplinary, and technology-assisted medication review programmes and their impact on prescribing appropriateness• Application and comparative performance of prescribing appropriateness tools (Beers Criteria, STOPP/START, MAI, FORTA) in real-world settings• Patient-reported outcomes and quality of life following medication reduction or withdrawal• Pharmacoepidemiological methods applied to polypharmacy and deprescribing research, including the use of EHRs, claims data, and registries• Cost of illness and resource-use studies of polypharmacy management strategies and deprescribing programmes• Prescribing policy, clinical guidelines, and quality indicators for multimorbid populations• Digital health and AI-assisted clinical decision support for the identification and reduction of inappropriate polypharmacy• Special populations including older adults, patients with frailty, those with multimorbidity in low- and middle-income countries, and end-of-life care settingsStudies employing quantitative, qualitative, and mixed-methods approaches are all within scope. Topic editors: Seungwon Kwon, Ramesh Sharma Poudel, Tesfahun Eshetie, Wubshet Tesfaye Source: https://www.frontiersin.org/research-topics/83628/polypharmacy-and-deprescribing-in-multimorbid-patients-real-world-outcomes-safety-and-prescribing-policy