Deprescribing Fall Risk–Increasing Drugs in Older Adults: Implementation Challenges and a Conceptual Framework from the DeFRID Trial and Global Evidence

Background Deprescribing fall risk–increasing drugs (FRIDs) is essential for reducing polypharmacy and falls in older adults, yet randomized controlled trials (RCTs) face unique implementation challenges. The DeFRID study is an ongoing multi-center RCT evaluating an ARMOR-based deprescribing intervention versus usual care in adults aged ≥60 years prescribed FRIDs. The objectives of this review are threefold: (1) to describe practical challenges encountered during a multi-center deprescribing RCT in India; (2) to propose a conceptual framework for categorizing these barriers; and (3) to contextualize DeFRID's experience within the broader deprescribing research landscape. Methods We conducted a narrative review with systematic scoping elements, synthesizing global RCT evidence from PubMed, OpenAlex, and Google Scholar (inception–December 2025) with DeFRID process evaluation data. DeFRID barriers and facilitators were identified via mixed-methods (clinician KAP questionnaire and qualitative interviews), team meetings, retention logs, and Phase II RCT implementation data, thematically categorized, then compared with global RCT challenges. Results DeFRID implementation revealed four challenge categories: ethical–clinical difficulties establishing equipoise for FRID withdrawal; operational barriers to recruitment and retention; methodological complexities in fall outcome ascertainment; and context-specific constraints unique to the Indian LMIC setting—limited deprescribing guidelines, polypharmacy normalization, fragmented care coordination, and hierarchical decision-making. Global RCTs revealed substantial implementation challenges: low clinician adherence, short follow-up periods, restrictive eligibility excluding frail or cognitively impaired older adults, and resource-intensive interventions limiting scalability. Conclusions Deprescribing FRIDs in older adults is impeded by ethical, operational, methodological, and provider-patient challenges, necessitating multilevel strategies integrating training, shared decision-making, context-specific guidelines, and stakeholder engagement for scalable implementation.