Optimizing Long-Term Proton Pump Inhibitor Therapy Through Deprescribing: A Critical Review of Current Evidence, Clinical Outcomes, and Future Perspectives

Background: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications worldwide for the management of acid-related disorders. However, prolonged use beyond evidence-based indications has become increasingly common, exposing patients to avoidable adverse effects and contributing to unnecessary healthcare expenditure. Objective: This review aims to critically evaluate current evidence regarding PPI deprescribing and de-escalation strategies, examine their clinical outcomes and safety profiles, and explore emerging stewardship approaches for optimizing long-term PPI therapy. Methods: Relevant original studies, randomized controlled trials, observational studies, pharmacovigilance analyses, and stewardship interventions published between 2010 and 2026 were reviewed using literature retrieved from PubMed, PubMed Central, and related databases. Results: Current evidence demonstrates that structured, patient-centered deprescribing interventions, including dose tapering, abrupt discontinuation, pharmacist-led stewardship programs, and multidisciplinary care models, can successfully reduce inappropriate long-term PPI use in a substantial proportion of patients. Although rebound acid hypersecretion remains a challenge, appropriate patient education, follow-up, and rescue therapy strategies improve deprescribing success. Emerging evidence also supports the cost-effectiveness and clinical benefits of structured PPI stewardship programs. Conclusion: PPI deprescribing represents an effective strategy for optimizing medication use while minimizing unnecessary exposure to long-term adverse effects. Future efforts should focus on individualized deprescribing approaches, clinical decision support systems, multidisciplinary stewardship programs, and implementation strategies that promote sustainable medication optimization.