Proton-Pump Inhibitor Therapy Induces Acid-Related Symptoms in Healthy Volunteers After Withdrawal of Therapy

Received 4 February 2009; accepted 31 March 2009. published online 13 April 2009.

Refers to article:

Evidence That Proton-Pump Inhibitor Therapy Induces the Symptoms it Is Used to Treat , 01 June 2009
Kenneth E.L. McColl, Derek Gillen
Gastroenterology
July 2009 (Vol. 137, Issue 1, Pages 20-22)
Full Text | Full-Text PDF (487 KB)

Background & Aims

Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). If RAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications.

Methods

A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom.

Results

There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPI group at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported ≥1 relevant, acid-related symptom in weeks 9–12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPI group was 13 of 59 (22%) at week 10, 13 of 59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001).

Conclusions

PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

Abbreviations used in this paper: CgA, chromogranin, PPI, proton-pump inhibitor, RAHS, rebound acid hypersecretion

⁎ Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark

‡ Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark

Reprint requests Peter Bytzer, MD, PhD, AGAF, Professor of Medicine, Copenhagen University, Køge University Hospital, Department of Medicine, Lykkebækvej 1, DK-4600 Køge, Denmark. fax: +45 5663 1552

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.

PII: S0016-5085(09)00522-8

doi:10.1053/j.gastro.2009.03.058

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