By Allan J. Wilke, MD

Professor and Chair, Family and Community Medicine, Western Michigan University Homer Stryker M.D. School of Medicine

Dr. Wilke reports no financial relationships relevant to this field of study.

SYNOPSIS: Researchers recently developed an evidence-based algorithm for reducing the use of proton pump inhibitors.

SOURCE: Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: Evidence-based clinical practice guideline. Can Fam Physician 2017;63:354-364.

Proton pump inhibitors (PPIs) are wonder drugs that have revolutionized our treatment of heartburn, esophagitis, gastric inflammation, and ulcer disease, making them among the most commonly prescribed medications in the United States. In 2015, esomeprazole (Nexium) was the fourth most commonly prescribed drug by number of monthly prescriptions with 15.2 million.1 A study from 2006 found that in the United States, more than $10 billion is spent annually on this class of medication,2 and it is safe to assume that we spend much more a decade later. The most common indications are heartburn and gastroesophageal reflux disease (GERD), and the recommended duration of treatment is four to eight weeks. A recommendation from the American Gastroenterological Association (AGA) states, “For pharmacological treatment of patients with [GERD], long-term acid suppression therapy ([PPIs] or histamine-2 receptor antagonists) should be titrated to the lowest effective dose needed to achieve therapeutic goals. The main identifiable risk associated with reducing or discontinuing acid suppression therapy is an increased symptom burden. It follows that the decision regarding the need for (and dosage of) maintenance therapy is driven by the impact of those residual symptoms on the patient’s quality of life rather than as a disease control measure.”3 Although generally considered safe, PPIs can produce many adverse side effects, including, but not limited to, fractures, hypomagnesemia, Clostridium difficile infection, diarrhea, vitamin B12 deficiency, pancreatitis, and blood dyscrasias. These adverse effects are worse in the elderly, who can experience difficulties metabolizing and eliminating medications.4 There are many reasons to stop PPIs beyond their possible adverse effects and expense. Polypharmacy, especially in the elderly, can lead to nonadherence, medication errors, and drug interactions. There is mounting evidence of their overuse.5 However, PPIs are notoriously difficult to stop once started.

An interdisciplinary group from Canada, comprised of family physicians, a gastroenterologist, pharmacists, a methodologist, pharmacy residents, project coordinators, a librarian, and a master’s student, described their method for devising a guideline to stop or reduce use of PPIs. The group chose to focus on adults taking PPIs for longer than 28 days to treat GERD or esophagitis; they excluded patients with Barrett’s esophagus, severe esophagitis, or a history of bleeding gastrointestinal ulcers. Using a previously published method for guideline development, they followed a checklist and reviewed the literature for articles that addressed stopping or reducing the dose of PPIs — or as they termed it, “deprescribing.”

Deprescribing can take several forms. First is “stopping,” either immediately or with a defined taper. Then there is “stepping down,” which is similar to stopping, except it is followed by a prescription for a histamine-2 receptor antagonist (H2RA). Finally, there is “reducing,” which includes either “on-demand use” (stopping use completely when symptoms resolve and then restarting, if symptoms return) and “lower dose” (reducing to a maintenance dose after symptoms resolve).

Their systematic review yielded several findings, which guided the decision tree. Asymptomatic patients who reduced their dose of a PPI were no more likely to relapse than patients who continued with the standard dose. On-demand use and stepping down increased the risk of relapse compared to lower dose, but had the benefit of a lower pill burden and cost.

Their algorithm, conveniently published in a flow chart, starts with a basic but important question: “Why is patient taking a PPI?” It includes exclusion criteria for patients who should continue PPIs, recommendations for monitoring and follow-up, and advice on nonpharmacological approaches to treat heartburn and GERD.


This article is important because, although the overuse of PPIs is well documented, we haven’t seen evidence-based advice on how to reverse it. As with every guideline, this one must be applied to the patient in front of you, and application should incorporate the patient’s goals of care. The Choosing Wisely campaign, an initiative created by the American Board of Internal Medicine Foundation, offers a patient handout developed by Consumer Reports and the American Gastroenterological Association to help clinicians educate patients about treating heartburn and GERD.6

As good as this is, it is not enough. Similar to the strategy for decreasing our country’s cesarean delivery rate, “don’t do the first one,” we need to think twice before we write the first PPI prescription. Have we recommended lifestyle changes (i.e., don’t eat two to three hours before bed, raise the head of the bed, lose weight, and avoid dietary triggers) as the first step? Patients and clinicians may view taking a pill as the path of least resistance, but once down that path, it is difficult to get back to where we once belonged.

The authors host a website devoted to deprescribing, naturally called It offers a page for healthcare professionals that contains algorithms for deprescribing benzodiazepines, antipsychotics, and antihyperglycemics, all drugs with especially adverse side effects in the elderly. 


  1. Brown T. The 10 Most-Prescribed and Top-Selling Medications. WebMD, May 8, 2015. Available at: Accessed June 19, 2017.
  2. Shaheen NJ, Hansen RA, Morgan DR, et al. The burden of gastrointestinal and liver diseases, 2006. Am J Gastroenterol 2006;101:2128-2138.
  3. Choosing Wisely. American Gastroenterological Association. Treating GERD, April 4, 2012. Available at: Accessed June 19, 2017.
  4. Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev 2009;41:67-76.
  5. Savarino V, Dulbecco P, de Bortoli N, et al. The appropriate use of proton pump inhibitors (PPIs): Need for a reappraisal. Eur J Intern Med 2017;37:19-24.
  6. Choosing Wisely. Treating Heartburn and GERD. Available at: Accessed June 19, 2017.