Purpose of Review
Proton pump inhibitors (PPIs) are effective for many conditions but are often overprescribed. Recent concerns about long-term risks have made patients re-evaluate their need to take PPIs chronically, though these population-based studies have methodological weaknesses. The goal of this review is to provide evidenced-based strategies for discontinuation of PPI therapy.
Given that some patients experience rebound symptoms when abruptly stopping continuous PPI therapy due to its effect on hypergastrinemia, strategies focus on avoiding rebound. Tapering the PPI and then initiating a “step-down” approach with the use of alternative medications may be effective. “On-demand therapy” provides patients with the option to take intermittent PPI courses, reducing overall use and cost while preserving patient satisfaction. It is important for providers to consider ambulatory pH or pH/impedance testing to rule out diagnoses that may require alternative medications like neuromodulators.
A number of studies reviewed here can provide guidance in counseling patients on PPI discontinuation. It is important for the provider to obtain a baseline needs assessment for PPI therapy and to elucidate predictors of difficulty in discontinuation prior to initiating a strategy.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336:2–3.
Gawron AJ, Feinglass J, Pandolfino JE, Tan BK, Bove MJ, Shintani-Smith S. Brand name and generic proton pump inhibitor prescriptions in the United States: insights from the national ambulatory medical care survey (2006-2010). Gastroenterol Res Pract. 2015;2015:689531.
Katz MH. Failing the acid test: benefits of proton pump inhibitors may not justify the risks for many users. Arch Intern Med. 2010;170:747–8.
Moayyedi P, Delaney BC, Vakil N, Forman D, Talley NJ. The efficacy of proton pump inhibitors in nonulcer dyspepsia: a systematic review and economic analysis. Gastroenterology. 2004;127:1329–37.
Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology. 2000;118:S9–31.
DeVault KR, Castell DO, American College of G. Updated guidelines for the diagnosis and treatment of gastroesophageal reflux disease. Am J Gastroenterol. 2005;100:190–200.
• Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152:706–15. Provides a critical review of studies suggesting PPI risks, allowing providers the ability to counsel patients effectively .
Heidelbaugh JJ, Goldberg KL, Inadomi JM. Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting. Am J Manag Care. 2010;16:e228–34.
Eid SM, Boueiz A, Paranji S, Mativo C, Landis R, Abougergi MS. Patterns and predictors of proton pump inhibitor overuse among academic and non-academic hospitalists. Intern Med. 2010;49:2561–8.
Lanas A. We are using too many PPIs, and we need to stop: a European perspective. Am J Gastroenterol. 2016;111:1085–6.
Mazer-Amirshahi M, Mullins PM, van den Anker J, Meltzer A, Pines JM. Rising rates of proton pump inhibitor prescribing in US emergency departments. Am J Emerg Med. 2014;32:618–22.
Zink DA, Pohlman M, Barnes M, Cannon ME. Long-term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21:1203–9.
Gomm W, von Holt K, Thome F, et al. Association of proton pump inhibitors with risk of dementia: a pharmacoepidemiological claims data analysis. JAMA Neurol. 2016;73:410–6.
Targownik LE, Leslie WD, Davison KS, et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: a population-based study [corrected] from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol. 2012;107:1361–9.
Furuya-Kanamori L, Stone JC, Clark J, et al. Comorbidities, exposure to medications, and the risk of community-acquired Clostridium difficile infection: a systematic review and meta-analysis. Infect Control Hosp Epidemiol. 2015;36:132–41.
Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One. 2015;10:e0128004.
Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310:2435–42.
Roman S, Gyawali CP, Savarino E, et al. Ambulatory reflux monitoring for diagnosis of gastro-esophageal reflux disease: update of the Porto consensus and recommendations from an international consensus group. Neurogastroenterol Motil. 2017;29:1–15.
Mainie I, Tutuian R, Shay S, et al. Acid and non-acid reflux in patients with persistent symptoms despite acid suppressive therapy: a multicentre study using combined ambulatory impedance-pH monitoring. Gut. 2006;55:1398–402.
Waldum HL, Arnestad JS, Brenna E, Eide I, Syversen U, Sandvik AK. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut. 1996;39:649–53.
•• Reimer C, Sondergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137:80–7. 87 e81. Provides a mechanism behind the phenomenon of rebound symptoms with PPI discontinuation.
Inadomi JM, Jamal R, Murata GH, et al. Step-down management of gastroesophageal reflux disease. Gastroenterology. 2001;121:1095–100.
•• 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;24:945–54. This randomized study found that certain factors like underlying diagnosis and gastrin level may affect ability for patients to discontinue PPI .
Pace F, Tonini M, Pallotta S, Molteni P, Porro GB. Systematic review: maintenance treatment of gastro-oesophageal reflux disease with proton pump inhibitors taken ‘on-demand’. Aliment Pharmacol Ther. 2007;26:195–204.
Bayerdorffer E, Bigard MA, Weiss W, et al. Randomized, multicenter study: on-demand versus continuous maintenance treatment with esomeprazole in patients with non-erosive gastroesophageal reflux disease. BMC Gastroenterol. 2016;16:48.
Hansen AN, Wahlqvist P, Jorgensen E, et al. Six-month management of patients following treatment for gastroesophageal reflux disease symptoms—a Norwegian randomized, prospective study comparing the costs and effectiveness of esomeprazole and ranitidine treatment strategies in a general medical practitioners setting. Int J Clin Pract. 2005;59:655–64.
Murie J, Allen J, Simmonds R, de Wet C. Glad you brought it up: a patient-centred programme to reduce proton-pump inhibitor prescribing in general medical practice. Qual Prim Care. 2012;20:141–8.
Leiman DA, Riff BP, Morgan S, et al. Alginate therapy is effective treatment for GERD symptoms: a systematic review and meta-analysis. Dis Esophagus. 2017;30:1–9.
Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016;150:1262–1279.e2.
Viazis N, Keyoglou A, Kanellopoulos AK, et al. Selective serotonin reuptake inhibitors for the treatment of hypersensitive esophagus: a randomized, double-blind, placebo-controlled study. Am J Gastroenterol. 2012;107:1662–7.
Nguyen TM, Eslick GD. Systematic review: the treatment of noncardiac chest pain with antidepressants. Aliment Pharmacol Ther. 2012;35:493–500.
Ligumsky M, Lysy J, Siguencia G, Friedlander Y. Effect of long-term, continuous versus alternate-day omeprazole therapy on serum gastrin in patients treated for reflux esophagitis. J Clin Gastroenterol. 2001;33:32–5.
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Esophagus
About this article
Cite this article
Kim, J., Blackett, J.W. & Jodorkovsky, D. Strategies for Effective Discontinuation of Proton Pump Inhibitors. Curr Gastroenterol Rep 20, 27 (2018). https://doi.org/10.1007/s11894-018-0632-y
- Proton pump inhibitors
- Step-down therapy
- On-demand therapy
- Reflux hypersensitivity