Safety of Long-Term PPI Use: A Clinical Assessment

Appropriate Indications for Long-Term PPI Use

The American Gastroenterological Association recommends long-term PPI use for patients with Barrett's esophagus, as it reduces the risk of esophageal adenocarcinoma 1, 2
The American Gastroenterological Association recommends long-term PPI use for patients with severe erosive esophagitis (Los Angeles Classification grade C/D) 3, 4
The American Gastroenterological Association recommends long-term PPI use for gastroprotection in high-risk NSAID/aspirin users 3
The American Gastroenterological Association recommends long-term PPI use for secondary prevention of gastric/duodenal ulcers 3
The American Gastroenterological Association conditionally recommends long-term PPI use for PPI-responsive endoscopy-negative reflux disease with symptom recurrence after discontinuation 3, 4
The American Gastroenterological Association conditionally recommends long-term PPI use for esophageal strictures from GERD 3
The American Gastroenterological Association conditionally recommends long-term PPI use for prevention of idiopathic pulmonary fibrosis progression 3, 1

The American Gastroenterological Association recommends regular indication review for patients on long-term PPI use, with documentation of ongoing indication 3, 5
The American Gastroenterological Association recommends consideration of de-prescribing for patients without a definitive indication for long-term PPI use 3, 5, 1
The American Gastroenterological Association recommends dose optimization, with step-down to once-daily dosing for patients on twice-daily dosing 6
The American Gastroenterological Association recommends against discontinuation of PPIs in high-risk patients, including those with complicated GERD, Barrett's esophagus, eosinophilic esophagitis, or idiopathic pulmonary fibrosis 5, 2, 7

Randomized controlled trials have not confirmed increased adverse events with long-term PPI use, despite observational associations 5
The American Gastroenterological Association notes that rebound acid hypersecretion is common after discontinuation of long-term PPI therapy, and patients should be warned about potential transient upper GI symptoms 7
The American Gastroenterological Association recommends either dose tapering or abrupt discontinuation when de-prescribing PPIs 7

The American Gastroenterological Association recommends not discontinuing PPIs solely due to concern about potential adverse events, including dementia, when a valid indication exists 8
Patients with valid indications for PPI use, such as severe erosive esophagitis, history of esophageal ulcer or peptic stricture, eosinophilic esophagitis with PPI response, high-risk NSAID/aspirin users requiring gastroprotection, secondary prevention of gastric/duodenal ulcers, and history of upper GI bleeding, should continue therapy 9

For patients without a clear indication for chronic PPI use, a trial of de-prescribing should be considered, with either dose tapering or abrupt discontinuation being acceptable 8
The American Gastroenterological Association explicitly states that all studies reporting associations between PPIs and dementia have been observational and cannot establish causality, while randomized controlled trials comparing PPIs with placebo have consistently shown no higher rate of any adverse events among PPI users 8

In geriatric patients with gastrointestinal issues requiring antiplatelet therapy or NSAIDs, the substantial risk reduction from PPIs for GI bleeding outweighs any theoretical dementia risk from observational studies 10
For patients requiring long-term therapy, the lowest effective dose should be used, with step down from twice-daily to once-daily dosing when appropriate 8