Randomised controlled trialindependent cross-checkabstract checked★ key study I-PPI-104 in-depth review
Stopping an acid blocker caused short-lived indigestion in healthy people
Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial.
Overview
Niklasson A et al.. Am J Gastroenterol 2010 · PMID 20332770 · DOI 10.1038/ajg.2010.81
After 4 weeks of pantoprazole, 44% of healthy volunteers developed indigestion when they stopped, compared with 9% after placebo; it faded within 3 weeks.
Does the study support the specific claim? Yes · Methodological quality: high
Plain-language summary
Study explained simply
- What did the researchers want to find out?
Test for rebound after stopping a PPI.
- How was the study done?
Double-blind RCT.
- How many people, animals or samples were studied?
48 healthy volunteers.
- What was actually found?
44% vs 9% developed indigestion; gone by week 3.
- How large was the observed effect?
RR about 5; NNH about 3.
- What do the results mean in everyday life?
Expect a few weeks of symptoms after stopping; it does not mean you need the drug.
- What are the study's limitations?
Small; short treatment.
- What does it say about Elawady's specific claim?
Supports rebound claim; limits 'dependence' claim.
- Do the results apply to Germany and Europe?
Applicable.
- What can explicitly not be concluded from this study?
Cannot show permanent dependence.
Scientific in-depth review
1. Full reference
- Authors
- Niklasson A et al.
- Journal
- Am J Gastroenterol
- Year
- 2010
- Identifier
- PMID 20332770 DOI 10.1038/ajg.2010.81
- Verification
- verified – PubMed efetch 2026-10-26 + Crossref 2026-10-26
- Retracted
- no
- Corrections
- none
- Extent checked
- abstract only
- Conflicts of interest and funding
Not stated in abstract
2. Research question
Does stopping a 4-week course of pantoprazole cause dyspeptic symptoms in healthy people?
3. Study design and population
- Study design
- Randomised controlled trial – Double-blind, placebo-controlled randomised trial in healthy volunteers
- Population
48 healthy H. pylori-negative volunteers (24 women)
- Country
Sweden
- Period
Published 2010
- Sample size
48 (25 pantoprazole, 23 placebo)
- Inclusion and exclusion criteria
Healthy, H. pylori-negative
4. Methods and endpoints
- Exposure / intervention
Pantoprazole 40 mg daily for 28 days, then stop
- Comparator
Placebo
- Endpoints
Glasgow dyspepsia score for 6 weeks after stopping; gastrin, chromogranin A
- Statistical methods
Group comparisons; correlation with gastrin
5. Actual results
- Results
Week 1 after stopping: mean score 5.7 +/- 11.7 vs 0.74 +/- 2.6 (P<0.01); 11/25 (44%) vs 2/23 (9%) developed dyspepsia (P<0.01); week 2: 1.6 vs 0 (P<0.05); no difference in week 3. Symptoms correlated with end-of-treatment gastrin.
- Absolute risks
44% vs 9% developed dyspepsia
- Authors' conclusion
A 4-week course of pantoprazole seems to induce dyspeptic symptoms in previously asymptomatic people, probably via rebound acid hypersecretion.
6. Strengths
- Double-blind placebo control
- Healthy participants avoid disease relapse confounding
7. Weaknesses
- Small
- Short treatment
- Transient effect
8. Risk of bias
- Orienting tool
- RoB 2
- Type of assessment
- simplified assessment (abstract only)
- Full formal assessment
- no
- Overall risk of bias
- low
- Rationale
Blinded; small sample.
9. Assessment of the statistical interpretation
Recomputed RR 5.06 (1.25-20.4), RD 35 points, NNH about 3 (stats/C-PPI-06_07_rebound_discontinuation.py); effect gone by week 3.
10. Relevance to the specific claim
Independent replication of Reimer 2009: stopping a PPI can cause new, short-lived symptoms in people who had none.
11. Independent contrary findings
Symptoms resolved by week 3.
12. Transferability to Germany and Europe
Applicable.
13. Overall methodological judgement
Confirms C-PPI-06; shows transience relevant to C-PPI-07.
| Multidimensional assessment | |
|---|---|
| Authenticity of the source | verified |
| Methodological quality | high |
| Risk of bias | low |
| Precision of results | low |
| Directness | direct |
| Reproducibility | replicated |
| Consistency with the overall evidence | consistent |
| Regional transferability | high |
| Adequacy of the interpretation (by the archive) | not applicable |
14. Open questions
Rebound after years of use.
15. Linked fact checks
- After stopping a PPI, rebound acid hypersecretion can cause new heartburn and reflux symptoms, even in people who had none before. – Studies supporting the claim
- PPIs create dependency: the drug 'manufactures the disease it claims to treat', so that a short course for a passing complaint turns into chronic dependence and one 'cannot stop'. – Studies with mixed or unclear results