Long-term proton pump inhibitor therapy in daily clinical practice – balancing benefits and potential risks: a narrative review

Abstract Background and Aim The introduction of proton pump inhibitors (PPIs) in the late 1980s revolutionized the management of acid-related diseases. However, their high efficacy and favorable safety profile have led to widespread overprescribing, with an estimated 30–50% of primary care patients taking them without clear clinical indications. This review aims to critically summarize the current state of medical knowledge regarding the clinical benefits, long-term multi-organ risks, and principles of safe PPI discontinuation based on contemporary clinical guidelines. Methods A comprehensive review of current medical literature and official guidelines from major scientific organizations (including the American Gastroenterological Association [AGA], and the American College of Gastroenterology [ACG] concerning indications, complications, and PPI deprescribing protocols was performed. Results Chronic PPI therapy is justified in severe gastroesophageal reflux disease (GERD grades C and D according to the Los Angeles classification), Barrett’s esophagus (for chemoprevention of high-grade dysplasia and adenocarcinoma), hypersecretory states (e.g., Zollinger-Ellison syndrome), and gastroprotection during NSAID or anticoagulant therapy in high-risk patients. Nonetheless, prolonged acid suppression (iatrogenic hypochlorhydria) is associated with significant systemic complications. These include nutritional deficiencies (vitamin B12, iron, magnesium, calcium), progressive bone demineralization (osteoporosis and low-energy fractures), increased susceptibility to infections (C. difficile, [SIBO], community-acquired pneumonia [CAP], subclinical renal injury (acute interstitial nephritis [AIN] leading to chronic kidney disease [CKD], fundic gland polyps [FGP], and drug-drug interactions (e.g., with clopidogrel or levothyroxine). The process of deprescribing is often hindered by Rebound Acid Hypersecretion [RAHS], which simulates a recurrence of the primary disease, prompts patients to resume medication, and establishes a clinical “vicious cycle”. Conclusions Modern clinical care for patients on long-term PPI therapy demands regular re-evaluation of treatment indications. If long-term therapy is no longer justified, a structured de-escalation plan consisting of gradual dose reduction (tapering), extension of dosing intervals, and transition to on-demand therapy is required to mitigate chronic risks and prevent RAHS symptoms.