Previous research suggests that stopping treatment with proton-pump inhibitors (PPIs) causes rebound hypersecretion of acid. The presumed mechanism is a PPI-induced increase in serum gastrin, which exerts trophic effects on acid-producing gastric cells. When a PPI is withdrawn, these cells are poised to hypersecrete acid. To examine the clinical implications of this phenomenon, Danish researchers conducted a double-blind randomized trial that involved 120 healthy volunteers with no substantial histories of heartburn or dyspepsia; participants received either 12 weeks of placebo or 8 weeks of esomeprazole (40 mg daily) followed by 4 weeks of placebo.
For the initial 8 weeks, mean symptom scores were similar in the esomeprazole and placebo groups. Scores diverged after esomeprazole recipients were switched to placebo; between weeks 9 and 12, mean scores for heartburn, regurgitation, and dyspepsia became modestly but significantly higher in the original esomeprazole group than in the continuous placebo group. In addition, during weeks 9 to 12, more people in the original esomeprazole group than in the placebo group reported symptoms (44% vs. 15%).
Comment: This study demonstrates that some people develop symptoms consistent with rebound hyperacidity when PPIs are stopped after 2 months of use. The findings are particularly pertinent for the many patients who take PPIs unnecessarily or for unclear indications: When we advise such patients to stop their PPIs, we should warn them about possible rebound. This complication perhaps is best managed with antacids, as rebound has also been described after stopping histamine (H2)-blocker therapy.
— Allan S. Brett, MD
Published in Journal Watch General Medicine July 14, 2009
