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Am Fam Physician. 2018;98(3):152-153

Author disclosure: No relevant financial affiliations.

Clinical Question

Are proton pump inhibitors (PPIs) effective in reducing the symptoms of functional dyspepsia?

Evidence-Based Answer

There is moderate-quality evidence that PPIs are more effective than placebo at relieving overall symptoms in patients with functional dyspepsia (number needed to treat [NNT] = 11). Low-quality evidence suggests a small benefit of PPI therapy compared with prokinetics, and little to no benefit of PPI therapy vs. histamine H2 antagonists. Treatment effect was independent of dose or duration of therapy, and the combination of a PPI plus a prokinetic agent did not provide additional benefit.1 (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Functional dyspepsia is a highly prevalent but poorly understood condition, affecting 10% to 15% of the U.S. population and accounting for 3% to 5% of North American primary care visits.2 The definition of functional dyspepsia has evolved over time, most recently characterized in the Rome IV criteria as having one or more of the following: postprandial fullness, early satiety, epigastric pain, or epigastric burning without evidence of structural disease.3 Gastric acid suppression is the most common treatment option, with PPIs being the most widely used agents. Despite their widespread use, the underlying therapeutic mechanism of PPIs in functional dyspepsia remains unclear.4 Given the developing concerns about long-term use of PPIs, including Clostridium difficile infection, pneumonia, and fracture risk,5 the authors of this review sought evidence supporting their clinical application.

This Cochrane review included 25 randomized controlled trials and 8,453 adult patients who met criteria for a diagnosis of functional dyspepsia. Included trials compared treatment with an orally administered PPI of any type to treatment with placebo, H2 antagonists (e.g., cimetidine [Tagamet]), or prokinetics (e.g., metoclopramide [Reglan]). Treatment duration was two to eight weeks, and both low-dose PPIs (equivalent to 10 mg of omeprazole [Prilosec]) and standard-dose PPIs (equivalent to 20 mg of omeprazole) were evaluated. Combination therapies involving PPIs were also considered. The primary outcome of the review was absence of global symptoms of dyspepsia or epigastric pain/discomfort.

Moderate-quality evidence demonstrated that PPI therapy was more effective than placebo in reducing global symptoms of dyspepsia, with 31% of the PPI group reporting no or minimal symptoms compared with 26% of the placebo group (relative risk [RR] = 0.88; 95% confidence interval [CI], 0.82 to 0.94; NNT = 11 [95% CI, 8 to 23]). PPI therapy may be only slightly more beneficial than prokinetic therapy at relieving global dyspepsia symptoms (RR = 0.89; 95% CI, 0.81 to 0.99; NNT = 16 [95% CI, 11 to 202]), although the quality of evidence was low because of imprecision and bias risk concerns. When PPIs were compared with H2 antagonists, there was no difference in the primary outcome. Low-dose PPI therapy had similar effectiveness to standard-dose therapy, and the combination of a PPI plus a prokinetic agent showed no additional benefit over PPI monotherapy.

Despite the demonstrated reduction in dyspepsia symptoms, data from six placebo-controlled studies investigating the effect of PPI therapy on quality-of-life metrics did not demonstrate a consistent difference. The review noted marked heterogeneity between studies in defining functional dyspepsia, reflecting its poorly understood pathophysiology and the evolution of guideline criteria. Despite this, subgroup analysis looking at reduction of dyspepsia symptoms based on Helicobacter pylori status, country of origin, presence of reflux, or Rome criteria did not show any significant deviation from the overall comparison. PPIs were well tolerated without an increase in short-term adverse effects when compared with placebo or other treatments.

The 2017 joint American College of Gastroenterology (ACG) and Canadian Association of Gastroenterology (CAG) guideline recommends standard-dose PPIs as first-line treatment in patients with H. pylori–negative functional dyspepsia. In patients who are H. pylori–positive, the ACG/CAG guideline also recommends PPI therapy if eradication is unsuccessful at eliminating symptoms.6 The findings of this review support the recommended use of PPIs in functional dyspepsia, although evidence suggests low-dose therapy is as effective as standard-dose therapy.

The practice recommendations in this activity are available at

Editor's Note: Some of the 95% confidence intervals in this Cochrane for Clinicians were calculated by the author based on raw data provided in the original Cochrane.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at

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