I read with interest the excellent review articles on gastroesophageal reflux disease (GERD) and functional dyspepsia in the March 2026 issue of the BCMJ [2026;68:62-68; 2026;68:69-75].

Considering the 4- to 8-week trials of proton-pump inhibitors frequently recommended and what are otherwise thoroughly comprehensive reviews, I note with concern the avoidance in both articles of even mentioning rebound acid hypersecretion as a side effect of proton-pump inhibitors.

This is a well-documented ubiquitous phenomenon, shown to exist in the 1980s (including with proof-of-concept physiological studies). It was proven clinically by placebo-controlled studies over 15 years ago (over 40% of previously asymptomatic volunteers suffered GERD symptoms following discontinuation of proton-pump inhibitors after 8 weeks of use). Worryingly, recent review articles cite multiple methodologically challenged studies and the need for better studies to risk stratify at patient populations, better identify clinically relevant outcomes, and develop efficacious withdrawal protocols.

While some of the indications for proton-pump inhibitors require long-term treatment, others do not.

A 4- to 8-week trial of therapy has a high likelihood of resulting in rebound acid hypersecretion.

Symptom relief after commencing proton-pump inhibitors occurs within a few days in most uncomplicated GERD patients (although mucosal healing will take longer).

In uncomplicated GERD patients, would it not be wiser to do a much shorter trial (less than 2 weeks) and assess symptomatic response within that time?

Considering the number of patients on long-term proton-pump inhibitor therapy and the unanswered rebound acid hypersecretion question, I hope for robust debate of the topic and look forward to a future article.
—Roger Seldon, MBChB, MD, CCFP
Campbell River

This letter was submitted in response to “Gastroesophageal reflux disease: Diagnosis and management in a primary care setting” and “Functional dyspepsia: Diagnosis and management in a primary care setting.” Read the authors’ response in “Re: Gastroesophageal reflux disease and functional dyspepsia. Authors reply.”

Additional reading

Ahmed A, Clarke JO. Proton pump inhibitors (PPI). StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2026. www.ncbi.nlm.nih.gov/books/NBK557385/.

Barraquer Comes A, Roy Millán P. Proton pump inhibitor deprescription prospective study in patients without indication: Are there differences in proportion of restarts according to withdrawal strategy? J Pharm Technol 2023;39:224-230. https://doi.org/10.1177/87551225231195216.

Namikawa K, Björnsson ES. Rebound acid hypersecretion after withdrawal of long-term proton pump inhibitor (PPI) treatment—Are PPIs addictive? Int J Mol Sci 2024;25:5459. https://doi.org/10.3390/ijms25105459.

Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009;137:80-87. https://doi.org/10.1053/j.gastro.2009.03.058.