PPIs—An easy ‘hi’ but a difficult goodbye

“We simply stop the PPI (proton pump inhibitor).” My PharmD student was explaining her strategy for some of her assignments. When given a scenario, the student perceived that the easiest way to decrease medication burden was to discontinue the PPI, leading to deprescribing success.Without experience, we often underestimate the difficulty of a task. Deprescribing can appear straightforward on paper, with tools, guidelines and algorithms. And PPIs are often used for symptoms rather than event prevention, so they are perceived to be low hanging fruit when approaching a patient with polypharmacy. But are they so easy to discontinue? Is this a good first choice for deprescribing in a patient with a complex medication regimen?PPI use There are many opportunities to deprescribe a PPI. Almost one-third of seniors in Canada have tried a PPI and almost one-quarter use this type of medication chronically.1 This is the second most commonly used drug class in older adults after statins. Canadian data show that the prevalence of gastroesophageal reflux disease (GERD) is close to 10%,2 but may be as high as 20%.3PPIs have become very common, are accessible and have public funding for older adults, and can be prescribed once daily with relatively good tolerance in patients. There are few complaints from patients taking PPIs; most of the side effects are silent or develop over a long period of time. The ease of starting a PPI in a practice setting where gastrointestinal complaints are common can lead to overuse of PPIs.Patient values Research has found that patients on PPIs place a very high value on symptom control.4 A recent study of more than 1,300 older adults found that cardiovascular medications were identified as those they would most like to discontinue, with medications for gastric acidity (which includes PPIs) as only the tenth most common type of medication to deprescribe. The most common reason older adults did not want to deprescribe a medication was because they perceived it as beneficial.5This study highlights that PPIs, unlike diuretics for example, are perceived as being quite well tolerated and effective, and therefore there is little perception from patients that these medications should be discontinued. This is not only patient perception; there is sound evidence that PPIs are extremely effective at managing symptoms and improving healing in GERD. A network meta-analysis ranked PPIs as up to 95% effective for symptom relief versus only 37% for H2-receptor antagonists (H2RAs).6 For nonpharmacologic interventions, in contrast, a study of bariatric surgery to address obesity found complete resolution of GERD symptoms in 65% of patients,7 and smoking cessation led to improvement in GERD in 44% of patients.8PPI safety One of the largest prospective randomized controlled trials also found that PPIs are very safe, with an increase in enteric infections (e.g., Clostridioides difficile), but no increase in fractures, kidney disease, pneumonia, mortality or other monitored side effects.9 This contrasts with some earlier observational studies that raised alarms about many different complications; but overall, it appears that PPIs are extremely effective and well tolerated. Long-term complications from acid suppression may still include vitamin or mineral deficiencies.10Other considerations Despite the lack of patient drive to discontinue PPIs, there are drug stewardship considerations, climate impact of unnecessary medications, and overall medication burden and polypharmacy that can cause harm.11 There are directives from organizations such as the American Geriatrics Society through their Beers Criteria to use PPIs for only eight weeks unless the patient is high risk.12 Guidelines from 2025 recommend de-escalating PPIs if patients have used them chronically for more than six months for GERD.13The overuse of PPIs should prompt clinicians to review guideline recommendations for nonpharmacologic approaches, such as dietary changes, weight loss, smoking cessation, changes in positioning of the bed for sleep, or switching away from tight fitting clothing.14 These interventions are evidence-based and can reduce GERD symptoms. If nonpharmacologic steps have been bypassed and the patient is on a PPI, deprescribing while simultaneously implementing nondrug measures can be presented.Deprescribing Various tapering methods are evidence-based, and could include lowering the dose of the PPI if possible, or switching to daily from twice-daily dosing, then taking the medication every other day. Other approaches include a full switch to an H2RA, then eventually stopping, or trying on-demand PPI therapy.11,15Rebound symptoms It is important to inform patients that they are quite likely to experience some rebound symptoms when reducing the dose or discontinuing their PPI. Studies have found that more than 40% of PPI-treated patients have rebound symptoms.16,17 Acid-producing parietal and enterochromaffin-like cell hyperplasia occurs during PPI therapy. Regression of hyperplasia (with reduced acid production) is estimated to take two to six months after PPI discontinuation, so rapid PPI tapering is not recommended.18When a chronic PPI is discontinued, rebound symptoms are more likely to be managed or resolved in patients who taper their medication while using other symptomatic treatments (e.g., antacids). One of the first PPI deprescribing studies found that only 15% of patients were asymptomatic upon PPI discontinuation without other medication.19SummaryGiven the preference-sensitive decision for patients to stop PPIs, you can present the range of options, with reassurance that you will be periodically checking in and supporting the deprescribing process over the coming six months.Cheryl A Sadowski is a professor at the Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, a clinical pharmacist at the Geriatric Outpatient Clinic at the Misericordia Community Hospital in Edmonton, Alberta, and a member of the Canadian Medication Appropriateness and Deprescribing Network.References:Canadian Institute for Health Information. Drug use among seniors in Canada. (accessed March 24, 2025).Dirac MA, Safiri S, Tsoi D, et al. The global, regional, and national burden of gastro-oesophageal reflux disease in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2020;5(6):561-81.Fedorak RN, Veldhuyzen van Zanten S, Bridges R. Canadian Digestive Health Foundation Public Impact Series: gastroesophageal reflux disease in Canada: incidence, prevalence, and direct and indirect economic impact. Can J Gastroenterol 2010;24(7):431-4. doi: 10.1155/2010/296584.Thompson W, Black C, Welch V, et al. Patient values and preferences surrounding proton pump inhibitor use: a scoping review. Patient 2018;11(1):17-28.Vidonscky Lüthold R, Jungo KT, Weir KR, et al. Older adults’ attitudes toward deprescribing in 14 countries. JAMA Netw Open 2025;8(2):e2457498. doi:10.1001/jamanetworkopen.2024.57498.Zhang C, Kwong JS, Yuan RX, et al. Effectiveness and tolerability of different recommended doses of PPIs and H2RAs in GERD: network meta-analysis and GRADE system. Sci Rep 2017;7:41021. doi: 10.1038/srep41021.Singh M, Lee J, Gupta N, et al. Weight loss can lead to resolution of gastroesophageal reflux disease symptoms: a prospective intervention trial. Obesity 2013;21(2):284-90.Kohata Y, Fujiwara Y, Watanabe T, et al. Long-term benefits of smoking cessation on gastroesophageal reflux disease and health-related quality of life. PloS One 2016;11(2):e0147860.Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 2019;157(3):682-91.e2.Haastrup PF, Thompson W, Søndergaard J, et al. Side effects of long-term proton pump inhibitor use: a review. Basic Clin Pharmacol Toxicol 2018;123(2):114-21.Farrell B, Lass E, Moayyedi P, et al. Reduce unnecessary use of proton pump inhibitors. BMJ 2022;379:e069211.2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2023;71(7):2052-81. doi: 10.1111/jgs.18372.Desai M, Ruan W, Thosani NC, et al. American Society for Gastrointestinal Endoscopy guideline on the diagnosis and management of GERD: summary and recommendations. Gastrointest Endosc 2025;101(2):267-84.Yadlapati R, Gyawali CP, Pandolfino JE. AGA clinical practice update on the personalized approach to the evaluation and management of GERD: expert review. Clin Gastroenterol Hepatol 2022;20(5):984-94.e1.Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician 2017;63(5):354-64.Reimer C, Søndergaard B, Hilsted L, et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009;137(1):80-7.e1.Niklasson A, Lindström L, Simrén M, et al. 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.Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology 2022;162(4):1334-42.Inadomi JM, Jamal R, Murata GH, et al. Step-down management of gastroesophageal reflux disease. Gastroenterology 2001;121(5):1095-100.