Background: The occurrence and the clinical relevance of rebound acid hypersecretion after discontinuation of proton pump inhibitors is unclear. Aim: To perform a systematic review of rebound acid hypersecretion after discontinuation of proton pump inhibitors. Methods: PubMed, Embase and Central were searched up to October 2005 with indexed terms. Results: Eight studies were included, sample size was 6-32. The studies used both basal and stimulated acid output as parameters to study rebound acid hypersecretion and assessed these at different time points and with variable methods. Five studies (including four randomized studies) did not find any evidence for rebound acid hypersecretion after proton pump inhibitor therapy. Of the remaining three studies, the duration of proton pump inhibitor therapy was the longest and two of these studies were the only to assess Helicobacter pylori status of their study subjects. These two studies suggested that rebound acid hypersecretion may occur in H. pylori-negatives after 8 weeks of proton pump inhibitors. Conclusions: Studies that have investigated rebound acid hypersecretion after cessation of proton pump inhibitor treatment are heterogenic in design, methods and outcome. There is some evidence from uncontrolled trials for an increased capacity to secrete acid in H. pylori-negative subjects after 8 weeks of treatment. There is no strong evidence for a clinically relevant increased acid production after withdrawal of proton pump inhibitor therapy.,
Alimentary Pharmacology and Therapeutics
Erasmus MC: University Medical Center Rotterdam

Hunfeld, N.G.M, Geus, W.P, & Kuipers, E.J. (2007). Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors. Alimentary Pharmacology and Therapeutics, 25(1), 39–46. doi:10.1111/j.1365-2036.2006.03171.x