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Meta-Analysis
. 2017 Mar 8;3(3):CD011194.
doi: 10.1002/14651858.CD011194.pub2.

Proton pump inhibitors for functional dyspepsia

Maria Ines Pinto-Sanchez  1 , Yuhong Yuan  1 , Premysl Bercik  1 , Paul Moayyedi  1
Affiliations
Meta-Analysis

Proton pump inhibitors for functional dyspepsia

Maria Ines Pinto-Sanchez et al. Cochrane Database Syst Rev. .

Update in

  • Proton pump inhibitors for functional dyspepsia.
    Pinto-Sanchez MI, Yuan Y, Hassan A, Bercik P, Moayyedi P. Pinto-Sanchez MI, et al. Cochrane Database Syst Rev. 2017 Nov 21;11(11):CD011194. doi: 10.1002/14651858.CD011194.pub3. Cochrane Database Syst Rev. 2017. PMID: 29161458 Free PMC article.

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.

Objectives: 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.

Search 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.

Selection criteria: 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).

Data collection and analysis: 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.

Main 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.

Authors' 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.

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Conflict of interest statement

MIPS: none known.

YY: none known.

PB: none known.

PM received funding for: research grants (AstraZeneca, Axcan), speaker's honorarium/educational presentations (AstraZeneca, Abbott Laboratories, Shire) and partial, unrestricted funding for his research chair at McMaster University, Hamilton, Canada (AstraZeneca).

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figure 3
Figure 3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figure 4
Figure 4
Funnel plot of comparison: 3 Proton pump inhibitors versus placebo, outcome: 3.1 Global symptoms (two to eight weeks).
Analysis 1.1
Analysis 1.1
Comparison 1 Standard‐dose versus low‐dose proton pump inhibitors (PPI), Outcome 1 Global symptoms of dyspepsia.
Analysis 2.1
Analysis 2.1
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 1 Global symptoms of dyspepsia (2 to 8 weeks).
Analysis 2.2
Analysis 2.2
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 2 Global symptoms of dyspepsia by duration of treatment.
Analysis 2.3
Analysis 2.3
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 3 Subgrouped by country of origin.
Analysis 2.4
Analysis 2.4
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 4 Subgrouped byHelicobacter pylori status.
Analysis 2.5
Analysis 2.5
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 5 Subgroup by PPI subtype.
Analysis 2.6
Analysis 2.6
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 6 Subgrouped by 24‐hour pH study.
Analysis 2.7
Analysis 2.7
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 7 Subgrouped by Rome III dyspepsia subtypes.
Analysis 2.8
Analysis 2.8
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 8 Subgrouped by low vs unclear vs high risk of bias.
Analysis 2.9
Analysis 2.9
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 9 Quality of life.
Analysis 2.10
Analysis 2.10
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 10 Adverse events.
Analysis 3.1
Analysis 3.1
Comparison 3 Proton pump inhibitors (PPI) versus H2 receptor antagonists (H2RA), Outcome 1 Global symptoms of dyspepsia.
Analysis 3.2
Analysis 3.2
Comparison 3 Proton pump inhibitors (PPI) versus H2 receptor antagonists (H2RA), Outcome 2 Adverse events.
Analysis 3.3
Analysis 3.3
Comparison 3 Proton pump inhibitors (PPI) versus H2 receptor antagonists (H2RA), Outcome 3 Exclusion of study published in abstract format/open‐label studies.
Analysis 4.1
Analysis 4.1
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 1 Global symptoms of dyspepsia (2 to 4 weeks).
Analysis 4.2
Analysis 4.2
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 2 Quality of life.
Analysis 4.3
Analysis 4.3
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 3 Adverse events.
Analysis 4.4
Analysis 4.4
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 4 Exclusion of studies published in abstract format.
Analysis 4.5
Analysis 4.5
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 5 Exclusion of open‐label studies.
Analysis 5.1
Analysis 5.1
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 1 Global symptoms of dyspepsia (2 to 4 weeks).
Analysis 5.2
Analysis 5.2
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 2 Quality of life.
Analysis 5.3
Analysis 5.3
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 3 Adverse events.
See this image and copyright information in PMC

References

References to studies included in this review

    1. Blum AL, Arnold R, Stolte M, Fischer M, Koelz HR. Short course acid suppressive treatment for patients with functional dyspepsia: results depend on Helicobacter pylori status. The Frosch Study Group. Gut 2000;47(4):473‐80. - PMC - PubMed
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References to studies excluded from this review

    1. Almazar AE, Saito YA, Locke G, Camillieru M, Burton DD, Bouras EP, et al. Is proton pump inhibitor use associated with delayed gastric emptying in functional dyspepsia subjects?. Gastroenterology 2015;148(4):S888.
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References to studies awaiting assessment

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References to ongoing studies

    1. From the Biomedical to the Biopsychosocial Model, From Theory to Practice.. Ongoing study March 2009..

Additional references

    1. Abraham NS, Moayyedi P, Daniels B, Veldhuyzen Van Zanten SJ. Systematic review: the methodological quality of trials affects estimates of treatment efficacy in functional (non‐ulcer) dyspepsia. Alimentary Pharmacology and Therapeutics 2004;19(6):631‐41. - PubMed
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    1. Bekhti A, Rutgeerts L. Domperidone in the treatment of functional dyspepsia in patients with delayed gastric emptying. Postgraduate Medical Journal 1979;55(Suppl 1):30‐2. - PubMed
    1. Bercík P, Verdú EF, Armstrong D, Idström JP, Cederberg C, Markert M, et al. The effect of ammonia on omeprazole‐induced reduction of gastric acidity in subjects with Helicobacter pylori infection. American Journal of Gastroenterology 2000;95(4):947‐55. - PubMed

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