Dyspeptic symptom development after discontinuation of a proton pump inhibitor: a double-blind placebo-controlled trial

Am J Gastroenterol. 2010 Jul;105(7):1531-7. doi: 10.1038/ajg.2010.81. Epub 2010 Mar 23.


Objectives: Conflicting data exist on whether discontinuation of proton pump inhibitors (PPIs) is associated with rebound secretion of gastric acid.

Methods: A total of 48 healthy Helicobacter pylori-negative volunteers (24 females) were randomized in a double-blinded manner to treatment with either pantoprazole 40 mg or placebo once daily for 28 days. Dyspeptic symptoms were registered daily using the Glasgow dyspepsia score (GDS) 2 weeks before, during, and 6 weeks after treatment. Plasma levels of gastrin and serum levels of chromogranin-A levels were measured before, during, and after treatment.

Results: During the 2 weeks before treatment, the placebo group had a mean GDS of 0.20 + or - 0.7 compared with the pantoprazole group score of 0.54 + or - 1.3 (NS). No significant differences between the symptom severity scores of the two groups were shown during the treatment period. During the first week after discontinuation of treatment, the pantoprazole group had a mean symptom score of 5.7 + or - 11.7 vs. 0.74 + or - 2.6 in the placebo group (P<0.01). A total of 11 out of 25 (44%) subjects in the pantoprazole group developed dyspepsia compared with 2 out of 23 (9%) in the placebo group (P<0.01). During the second week of follow-up, the pantoprazole group had a mean symptom score of 1.6 + or - 3.4 compared with 0 + or - 0 in the placebo group (P<0.05). There were no significant differences in the mean symptom score for the pantoprazole group (1.1 + or - 0.6) compared with the placebo group (0.4 + or - 0.3) during the third week of follow-up. Symptom scores during the first week after treatment correlated with basal (P<0.01) and meal-stimulated (P<0.01) gastrin levels at the end of treatment.

Conclusions: A 4-week course of pantoprazole seems to induce dyspeptic symptoms in previously asymptomatic healthy H. pylori-negative subjects. The correlation between symptom score and gastrin levels suggests that these symptoms are due to acid rebound hypersecretion and seem to be related to the degree of acid inhibition.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • 2-Pyridinylmethylsulfinylbenzimidazoles / administration & dosage*
  • 2-Pyridinylmethylsulfinylbenzimidazoles / adverse effects
  • Adult
  • Aged
  • Chromogranin A / blood
  • Double-Blind Method
  • Dyspepsia / drug therapy
  • Dyspepsia / epidemiology*
  • Female
  • Gastric Acid / metabolism*
  • Gastrins / blood
  • Humans
  • Male
  • Middle Aged
  • Pantoprazole
  • Placebos
  • Proton Pump Inhibitors / administration & dosage*
  • Proton Pump Inhibitors / adverse effects
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Surveys and Questionnaires
  • Sweden / epidemiology


  • 2-Pyridinylmethylsulfinylbenzimidazoles
  • Chromogranin A
  • Gastrins
  • Placebos
  • Proton Pump Inhibitors
  • Pantoprazole