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Meta-Analysis
. 2017 Nov 21;11(11):CD011194.
doi: 10.1002/14651858.CD011194.pub3.

Proton pump inhibitors for functional dyspepsia

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

Proton pump inhibitors for functional dyspepsia

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

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 May 2017), MEDLINE (OvidSP; to May 2017), Embase (OvidSP; to May 2017), and SIGLE grey literature (up to May 2017) and clinical trial registries; we handsearched abstracts from conferences up to May 2017. 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 of at least two weeks' duration. 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 and 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 25 RCTs from 27 papers (with 8453 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. PPI was 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 = 6172; studies = 18; number needed to treat for an additional beneficial outcome (NNTB) 11; moderate quality evidence). PPIs may have little or no effect compared with H2RAs (RR 0.88, 95% CI 0.74 to 1.04; participants = 740; studies = 2; low quality evidence), and may be slightly more effective than prokinetics (RR 0.89, 95% CI 0.81 to 0.99; participants = 1033; studies = 5; NNTB 16; low quality evidence) at relieving overall dyspepsia symptoms in people with FD. PPIs plus prokinetics have probably little or no effect compared with PPIs alone at relieving overall dyspepsia symptoms (RR 0.85, 95% CI 0.68 to 1.08; participants = 407; studies = 2; moderate quality evidence).There 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. There were fewer adverse events in the combination of PPI plus prokinetics compared to prokinetics alone (RR 0.60, 95% CI 0.39 to 0.93; participants = 407; studies = 2; moderate quality evidence).

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 prokinetics 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.

PubMed Disclaimer

Conflict of interest statement

MIPS: none known.

YY: none known.

AH: none known.

PB: none known.

PM has acted as a consultant and/or received speaker fees from Allergan, Shire and Lupin none of which directly or indirectly profit from PPI therapy. He also has received a research grant from Takeda to evaluate the diet and microbiome in IBS and IBD as part of the IMAGINE network but this company does sell a PPI.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Funnel plot of comparison: 3 Proton pump inhibitors versus placebo, outcome: 3.1 Global symptoms (two to eight weeks).
1.1
1.1. Analysis
Comparison 1 Standard‐dose versus low‐dose proton pump inhibitors (PPI), Outcome 1 Global symptoms of dyspepsia.
2.1
2.1. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 1 Global symptoms of dyspepsia.
2.2
2.2. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 2 Global symptoms of dyspepsia by duration of treatment.
2.3
2.3. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 3 Subgrouped by country of origin.
2.4
2.4. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 4 Subgrouped byHelicobacter pylori status.
2.5
2.5. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 5 Subgroup by PPI subtype.
2.6
2.6. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 6 Subgrouped by 24‐hour pH study.
2.7
2.7. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 7 Subgrouped by Rome III dyspepsia subtypes.
2.8
2.8. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 8 Subgrouped by low vs unclear vs high risk of bias.
2.9
2.9. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 9 Subgrouped by publication type.
2.10
2.10. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 10 Quality of life.
2.11
2.11. Analysis
Comparison 2 Proton pump inhibitors (PPI) versus placebo, Outcome 11 Adverse events.
3.1
3.1. Analysis
Comparison 3 Proton pump inhibitors (PPI) versus H2 receptor antagonists (H2RA), Outcome 1 Global symptoms of dyspepsia.
3.2
3.2. Analysis
Comparison 3 Proton pump inhibitors (PPI) versus H2 receptor antagonists (H2RA), Outcome 2 Adverse events.
4.1
4.1. Analysis
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 1 Global symptoms of dyspepsia (2‐4 weeks).
4.2
4.2. Analysis
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 2 Quality of life.
4.3
4.3. Analysis
Comparison 4 Proton pump inhibitors (PPI) versus prokinetics, Outcome 3 Adverse events.
5.1
5.1. Analysis
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 1 Global symptoms of dyspepsia (2‐4 weeks).
5.2
5.2. Analysis
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 2 Quality of life.
5.3
5.3. Analysis
Comparison 5 Proton pump inhibitors (PPI) plus prokinetics versus prokinetics alone, Outcome 3 Adverse events.
See this image and copyright information in PMC

Update of

Comment in

References

References to studies included in this review

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Schwartz 2001 {published data only}
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References to other published versions of this review

Pinto‐Sanchez 2017
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