Clinical—Alimentary TractProton-Pump Inhibitor Therapy Induces Acid-Related Symptoms in Healthy Volunteers After Withdrawal of Therapy
Section snippets
Participants
A randomized, double-blind, placebo-controlled trial was conducted between September 2007 and March 2008 at Køge University Hospital, Denmark. Healthy volunteers without acid-related disease or symptoms were chosen as our study population to establish that the symptoms observed were actually symptoms caused by the acid rebound phenomenon and not relapse of symptoms of underlying disease after discontinuation of treatment.
We advertised for healthy volunteers in student papers, on a student web
Results
Supplementary Figure 1 shows the trial profile. Table 1 shows study participants' baseline demographic and other characteristics. The PPI group was comparable to the placebo group in terms of age, gender, body mass index, smoking, alcohol habits, GSRS and SF-36 scores, previous acid-related symptoms ever, P-gastrin, and P-CgA levels. A significantly higher proportion or participants (13% vs 2%; P = .02) in the placebo group was H pylori positive.
Compliance, defined as intake of >90% of
Discussion
The results of our study indicate and support the hypothesis that the RAHS is clinically significant. Treatment with a PPI (esomeprazole 40 mg once daily) for 8 weeks induces acid-related symptoms like heartburn, acid regurgitation, and dyspepsia once treatment is withdrawn. The symptoms observed in our trial caused mild to moderate discomfort and appeared for the majority of subjects in the first 2 weeks after withdrawal of PPI. The observation that >40% of healthy volunteers, who have never
Conclusion
Acid inhibition with a PPI for 8 weeks induces acid-related symptoms in a significant proportion of asymptomatic subjects when therapy is withdrawn. We find it highly likely that the symptoms observed in this trial are caused by RAHS and that this phenomenon is equally relevant in patients treated long term with PPIs. These results justify the speculation that PPI dependency could be 1 of the explanations for the rapidly and continuously increasing use of PPIs.
Acknowledgments
The authors thank Jane Lancaster for expert technical assistance on gastrin and CgA analyses.
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Conflicts of interest The authors disclose the following: Peter Bytzer has consulted for and received honoraria and research funding from manufacturers of proton-pump inhibitors (AstraZeneca, Wyeth, Nycomed, Eisai). Bo Søndergaard has received honoraria from Wyeth. The remaining authors disclose no conflicts.
Funding The study received funding through the Danish Medical Research Council, Københavns Amts Research Foundation and Region Sjællands Research Foundation. The medication and placebo was provided by AstraZeneca.