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New guidance from the American Gastroenterological Association recommends that physicians consider de-prescribing proton pump inhibitors (PPIs) for any patient on chronic PPIs without a clear indication, and step-down dosing for those on twice-daily treatment.

The expert review focuses on three domains: documentation of an indication for PPI usage, identification of suitable candidates for whom de-prescribing may be appropriate, and how to successfully go about de-prescribing.

"The decisions about PPI discontinuation are complex and nuanced, and consequences for inappropriate or poorly considered discontinuation can be significant," wrote Laura Targownik, MD, of the University of Toronto, and colleagues in . "Conversely, the unchecked use of PPIs in situations when indications are absent or murky is a major contributor to health care costs, and even a small risk of medical harm is significant in the complete absence of benefit."

In their list of "best practices," de-prescribing is not recommended for patients with complicated cases of gastroesophageal reflux disease (GERD), eosinophilic esophagitis, idiopathic pulmonary fibrosis, or Barrett's esophagus, as well as for those with a high risk of upper gastrointestinal (GI) bleeding.

For cases where de-prescribing is trialed, abrupt or tapered dosing may be considered, as the one trial comparing the two approaches found in the odds of patients being off PPIs and symptom-free at 6 months (31% with dose tapering over 3 weeks vs 22% with abrupt discontinuation).

"In health care settings with the infrastructure to review medication use, misuse, or overuse more broadly, a pharmacist- or nurse-specialist-centered multidisciplinary approach may facilitate systematic identification of inappropriate PPI use and de-prescribing," the authors wrote.

The 10 best practice recommendations are as follows:

1. For all patients on PPIs, primary care physicians should conduct a regular review of ongoing indications for use and document any indication for continued use
2. De-prescribing should be considered for any patients on chronic PPIs without a definitive indication
3. The majority of patients on twice-daily PPI dosing should be considered for once-daily step-down dosing
4. PPIs should not be discontinued for those with complicated GERD, including patients who have a prior history of severe peptic structure, esophageal ulcers, or erosive esophagitis
5. A trial of PPI de-prescribing should also not be considered for those with eosinophilic esophagitis, idiopathic pulmonary fibrosis, or Barrett's esophagus, where it has been shown to lower the risk of
6. Physicians should use an evidence-based strategy assessing the risk of upper GI bleeding before a trial of de-prescribing -- patients at risk may include those with a history of such bleeds and those on multiple antithrombotics, among others
7. If patients are at high risk for upper GI bleeds, such as those with the rare Zollinger-Ellison syndrome, PPIs should not be discontinued
8. Due to rebound acid hypersecretion, physicians should advise those discontinuing long-term (over 8 weeks) PPIs of the risk of transient upper GI symptoms
9. Abrupt discontinuation or dose tapering can be used to de-prescribe PPIs
10. De-prescribing decisions should be solely based on the absence of a PPI use indication -- not because of concerns over potential PPI-associated adverse events

Targownik and colleagues noted that the use of PPIs has been increasing over time in both the U.S. and worldwide -- roughly 7% to 15% of individuals have received the acid suppressors for some duration of time, which increases to 40% for those ages 70 and older. Potential risks of long-term use may include dementia, chronic kidney disease, and fractures, according to observational studies, though randomized trials have not shown such risks.

"Nonetheless, this body of literature has raised concerns among prescribers and patients about the long-term safety of PPIs. This concern may promote inappropriate discontinuation of PPIs when a strong indication for use exists," the authors cautioned.

About 40% of patients have attempted to discontinue PPIs due to the risk of treatment-related complications, and most did so without their physician's advice, they noted.

Regarding twice-daily dosing, the authors noted that the FDA has not approved such usage -- nor has it been studied in randomized trials -- and that higher doses may put patients at greater risk for complications. In one study in taking higher doses, 80% were able to step down to standard dosing without a significant change in symptoms.

In those who experience upper GI symptoms due to rebound acid hypersecretion following withdrawal, the group suggested "as-needed H2-receptor antagonists and/or contact antacids." Symptoms severely persisting for over 2 months post-discontinuation suggest a continued indication for PPI therapy, they noted.

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