title: Proton pump inhibitors for functional dyspepsia.
abstract: BACKGROUND
  Functional dyspepsia (FD or non-ulcer dyspepsia) is defined as continuous or frequently recurring epigastric pain or discomfort for which no organic cause can be found. Acid suppressive therapy, including proton pump inhibitors (PPIs), has been proposed as a therapeutic option in FD, but its efficacy remains controversial. While PPIs are generally considered safe and well tolerated, they have been associated with adverse events, especially in the long term. For this reason, decisions on whether to initiate or continue PPI therapy should be made based on an appropriate clinical indication. Therefore, we conducted a systematic review to evaluate whether PPI therapy provides symptomatic relief in FD.
  
  
  OBJECTIVE
  To determine the efficacy of proton pump inhibitors in the improvement of global symptoms of dyspepsia and quality of life compared to placebo, H2 receptor antagonists or prokinetics, in people with functional dyspepsia.
  
  
  METHODS
  We searched in the following electronic databases: the Cochrane Library (to January 2016), MEDLINE (OvidSP; to February 2016), Embase (OvidSP; to February 2016), and SIGLE grey literature (up to February 2016) and clinical trial registries; we handsearched abstracts from conferences up to February 2016. We screened non-systematic reviews, systematic reviews and guidelines to identify any additional trials. We contacted trialists to obtain missing information.
  
  
  METHODS
  All randomized controlled trials (RCTs) comparing any PPI with placebo, H2 receptor antagonists (H2RAs) or prokinetics for the treatment of FD. Participants were adults (aged 16 years or greater) with an adequate diagnosis of FD (any validated criteria such as Rome I, II, III or Lancet Working Group).
  
  
  METHODS
  Two review authors independently assessed eligibility, trial quality and extracted data. We collected data on dyspeptic symptoms, quality of life and number of overall adverse events. Specific adverse events were beyond the scope of this review.
  
  
  RESULTS
  We identified 23 RCTs from 22 papers (with 8759 participants) studying the effect of PPIs versus placebo, H2RAs or prokinetics for improvement of global symptoms of dyspepsia and quality of life in people with FD. Low-dose PPIs had similar efficacy as standard-dose PPIs, therefore we combined these subgroups for the analysis. Two to eight weeks of therapy with PPI was slightly more effective than placebo at relieving overall dyspepsia symptoms in people with FD (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.82 to 0.94; participants = 5968; studies = 16; number needed to treat for an additional beneficial outcome (NNTB) 13; moderate quality evidence). PPIs may be slightly more effective than H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2, NNTB 13; low quality evidence), and slightly more effective than prokinetics (RR 0.90, 95% CI 0.81 to 1.00; participants = 892; studies = 4; NNTB 20; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics were possibly slightly more effective than PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; NNTB 18; moderate quality evidence).The was no difference when subgrouped by Helicobacter pylori status, country of origin, or presence of reflux or Rome III subtypes. There were no differences in the number of adverse events observed between PPIs and any of the other treatments.
  
  
  CONCLUSIONS
  There is evidence that PPIs are effective for the treatment of FD, independent of the dose and duration of treatment compared with placebo. PPIs may be slightly more effective than H2RAs for the treatment of FD; however, the evidence is scarce. The trials evaluating PPIs versus prokinetics are difficult to interpret as they are at risk of bias. Although the effect of these drugs seems to be small, the drugs are well tolerated.
authors.affiliation: Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada.
authors.forename: Maria Ines
authors.initials: MI
authors.lastname: Pinto-Sanchez
authors.affiliation: Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada.
authors.forename: Premysl
authors.initials: P
authors.lastname: Bercik
authors.affiliation: Department of Medicine, Division of Gastroenterology, McMaster University, Hamilton, ON, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Moayyedi
mesh_terms: D004415:Dyspepsia / Q000188:drug therapy*; D006635:Histamine H2 Antagonists / Q000627:therapeutic use; D006801:Humans; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors