Gastroenterology
Volume 137, Issue 1 , Pages 80-87.e1 , July 2009

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

  • Christina Reimer

      Affiliations

    • Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark
  • ,
  • Bo Søndergaard

      Affiliations

    • Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark
  • ,
  • Linda Hilsted

      Affiliations

    • Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
  • ,
  • Peter Bytzer

      Affiliations

    • Department of Medical Gastroenterology, Køge University Hospital, Copenhagen University, Copenhagen, Denmark
    • Corresponding Author InformationReprint 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

Received 4 February 2009 ,Accepted 31 March 2009.

References 

  1. Danish Medicines Agency. Medicinal product statistics in Denmark 2007. Copenhagen: Danish Medicines Agency; 2008;
  2. Lassen A, Hallas J, Schaffalitzky de Muckadell OB. Use of anti-secretory medication: a population-based cohort study. Aliment Pharmacol Ther. 2004;20:577–583
  3. National Institute for Clinical Excellence (NICE). NICE clinical guideline 17 (Dyspepsia-management of dyspepsia in adults in primary care). London: NICE; 2004;
  4. Talley NJ, Vakil N. Guidelines for the management of dyspepsia. Am J Gastroenterol. 2005;100:2324–2337
  5. National Institute for Clinical Excellence (NICE). 2000/022 NICE issues guidance on proton pump inhibitors for dyspepsia. 2000;London, UK
  6. Raghunath AS, O'Morain C, McLoughlin RC. Review article: the long-term use of proton-pump inhibitors. Aliment Pharmacol Ther. 2005;22(Suppl 1):55–63
  7. Van Soest EM, Siersema PD, Dieleman JP, et al. Persistence and adherence to proton pump inhibitors in daily clinical practice. Aliment Pharmacol Ther. 2006;24:377–385
  8. Martin RM, Lim AG, Kerry SM, et al. Trends in prescribing H2-receptor antagonists and proton pump inhibitors in primary care. Aliment Pharmacol Ther. 1998;12:797–805
  9. Pollock K, Grime J. The cost and cost-effectiveness of PPIs—GP perspectives and responses to a prescribing dilemma and their implications for the development of patient-centred healthcare. Eur J Gen Pract. 2003;9:126–133
  10. Gillen D, Wirz AA, Ardill JE, et al. Rebound hypersecretion after omeprazole and its relation to on-treatment acid suppression and Helicobacter pylori status. Gastroenterology. 1999;116:239–247
  11. Waldum HL, Arnestad JS, Brenna E, et al. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut. 1996;39:649–653
  12. Hunfeld NG, Geus WP, Kuipers EJ. Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors. Aliment Pharmacol Ther. 2007;25:39–46
  13. US Food and Drug Administration. Rebound of gastric acid secretion. http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3650b1a_11.pdf2000;Accessed March 17, 2009
  14. Laine L, Ahnen D, McClain C, et al. Review article: potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2000;14:651–668
  15. Sanduleanu S, Stridsberg M, Jonkers D, et al. Serum gastrin and chromogranin A during medium- and long-term acid suppressive therapy: a case-control study. Aliment Pharmacol Ther. 1999;13:145–153
  16. Waldum HL, Sandvik AK, Syversen U, et al. The enterochromaffin-like (ECL) cell (Physiological and pathophysiological role). Acta Oncol. 1993;32:141–147
  17. Revicki DA, Wood M, Wiklund I, et al. Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease. Qual Life Res. 1998;7:75–83
  18. Dimenas E, Glise H, Hallerback B, et al. Well-being and gastrointestinal symptoms among patients referred to endoscopy owing to suspected duodenal ulcer. Scand J Gastroenterol. 1995;30:1046–1052
  19. Kulich KR, Madisch A, Pacini F, et al. Reliability and validity of the Gastrointestinal Symptom Rating Scale (GSRS) and Quality of Life in Reflux and Dyspepsia (QOLRAD) questionnaire in dyspepsia: a six-country study. Health Qual Life Outcomes. 2008;6:12
  20. Ware JE. Physical and mental health summary scales: a user's manual. Boston: The Health Institute, New England Medical Center; 2008;
  21. Borglum T, Rehfeld JF, Drivsholm LB, et al. Processing-independent quantitation of chromogranin a in plasma from patients with neuroendocrine tumors and small-cell lung carcinomas. Clin Chem. 2007;53:438–446
  22. Hilsted L, Rehfeld JF. Measurement of precursors for alpha-amidated hormones by radioimmunoassay of glycine-extended peptides after trypsin-carboxypeptidase B cleavage. Anal Biochem. 1986;152:119–126
  23. Lindberg G, Vieri J. Dyspepsia after withdrawal of omeprazole in healthy volunteers. Gastroenterology. 2003;124(Suppl 1):A-225
  24. Sharma BK, Walt RP, Pounder RE, et al. Optimal dose of oral omeprazole for maximal 24 hour decrease of intragastric acidity. Gut. 1984;25:957–964
  25. Bell N, Karol MD, Sachs G, et al. Duration of effect of lansoprazole on gastric pH and acid secretion in normal male volunteers. Aliment Pharmacol Ther. 2001;15:105–113
  26. Sharma B, Axelson M, Pounder RP, et al. Acid secretory capacity and plasma gastrin concentration after administration of omeprazole to normal subjects. Aliment Pharmacol Ther. 1987;1:67–76
  27. Niklasson A, Lindström L, Simren M, et al. Dyspeptic symptom development after discontinuation of a proton pump inhibitor: clinical importance of acid-rebound. Gastroenterology. 2008;134(Suppl 1):
  28. Gillen D, Wirz AA, Neithercut WD, et al. Helicobacter pylori infection potentiates the inhibition of gastric acid secretion by omeprazole. Gut. 1999;44:468–475
  29. Hunfeld NG, Geus WP, Kuipers EJ. Systematic review: Rebound acid hypersecretion after therapy with proton pump inhibitors. Aliment Pharmacol Ther. 2007;25:39–46
  30. Sanduleanu S, De Bruine A, Stridsberg M, et al. Serum chromogranin A as a screening test for gastric enterochromaffin-like cell hyperplasia during acid-suppressive therapy. Eur J Clin Invest. 2001;31:802–811
  31. D'Adda T, Pilato FP, Lazzaroni M, et al. Ultrastructural morphometry of gastric endocrine cells before and after omeprazole (A study in the oxyntic mucosa of duodenal ulcer patients). Gastroenterology. 1991;100:1563–1570
  32. Smith AD, Gillen D, Cochran KM, et al. Dyspepsia on withdrawal of ranitidine in previously asymptomatic volunteers. Am J Gastroenterol. 1999;94:1209–1213
  33. Qvigstad G, Arnestad JS, Brenna E, et al. Treatment with proton pump inhibitors induces tolerance to histamine-2 receptor antagonists in Helicobacter pylori-negative patients. Scand J Gastroenterol. 1998;33:1244–1248
  34. Bjornsson E, Abrahamsson H, Simren M, et al. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006;24:945–954
  35. Raghunath AS, Hungin AP, Mason J, et al. Helicobacter pylori eradication in long-term proton pump inhibitor users in primary care: a randomized controlled trial. Aliment Pharmacol Ther. 2007;25:585–592
  36. Wiklund I, Carlsson J, Vakil N. Gastroesophageal reflux symptoms and well-being in a random sample of the general population of a Swedish community. Am J Gastroenterol. 2006;101:18–28
  37. Wiklund IK, Junghard O, Grace E, et al. Quality of life in reflux and dyspepsia patients (Psychometric documentation of a new disease-specific questionnaire (QOLRAD)). Eur J Surg Suppl. 1998;41–49
  38. Naunton M, Peterson GM, Bleasel MD. Overuse of proton pump inhibitors. J Clin Pharm Ther. 2000;25:333–340
  39. Fossmark R, Johnsen G, Johanessen E, et al. Rebound acid hypersecretion after long-term inhibition of gastric acid secretion. Aliment Pharmacol Ther. 2005;21:149–154

 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

Gastroenterology
Volume 137, Issue 1 , Pages 80-87.e1 , July 2009