Treatment with proton pump inhibitors (PPIs) for eight weeks induces acid-related symptoms such as heartburn, acid regurgitation, and dyspepsia after treatment is withdrawn in healthy individuals, according to a new study in Gastroenterology.
"The observation that more than 40 percent of healthy volunteers, who have never been bothered by heartburn, acid regurgitation or dyspepsia, develop such symptoms in the weeks after cessation of PPIs is remarkable and has potentially important clinical and economic implications," said Dr. Christina Reimer of Copenhagen University, lead author of the study. "This study indicates unrecognized aspects of PPI withdrawal and is a very strong indication of a clinically significant acid rebound phenomenon that needs to be investigated in proper patient populations."
The use of PPIs for acid-related symptoms and disorders escalating rapidly. Although the incidence of new patients being treated with PPIs remains stable, the prevalence of long-term treatment is rising, the reasons for which are not fully known.
Studies have shown that up to 33 percent of patients who initiate PPI treatment continue to refill their prescriptions without an obvious indication for maintenance therapy. Rebound acid hypersecretion, defined as an increase in gastric acid secretion above pre-treatment levels following antisecretory therapy, is observed within two weeks after withdrawal of treatment and could theoretically lead to acid-related symptoms such as heartburn, acid regurgitation or dyspepsia that might result in resumption of therapy.
Researchers aimed to determine the clinical relevance of rebound acid hypersecretion to establish whether long-term treatment with a PPI creates a need for continuous treatment. A total of 120 healthy participants were tested randomly in 12 weeks of placebo or eight weeks of esomeprazole (40 mg per day), followed by four weeks with placebo. The symptoms observed in this trial caused mild to moderate discomfort and appeared for the majority of subjects in the first two weeks after withdrawal of therapy.
"We find it highly likely that the symptoms observed in this trial are caused by rebound acid hypersecretion and that this phenomenon is equally relevant in patients treated long term with PPIs," Reimer said. "If rebound acid hypersecretion induces acid-related symptoms, this might lead to PPI dependency. Our results justify the speculation that PPI dependency could be one of the explanations for the rapidly and continuously increasing use of PPIs."
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