This article is the summary/review of the following article:
Pinto-Sanchez, M. I., Yuan, Y., Hassan, A., Bercik, P., & Moayyedi, P. (2017). Protonpump inhibitors for functional dyspepsia (review). Cochrane Database of Systematic Reviews, CD011194. doi:10.1002/14651858.CD011194.pub3
Functional dyspepsia (FD) has traditionally been described as chronically occurring epigastric pain for which no specific cause can be identified. In addition, upper abdominal bloating, burping, and/or early satiety are often present. Although a normal upper endoscopy rules out disease process, it has not been beneficial in guiding symptom management. More recently, FD has been included in a group of disorders now called disorders of gut-brain interaction. The Rome Classification is a set of criteria used to describe the pathophysiology, symptoms, and treatment recommendations for these disorders. The Rome IV algorithms are the most current and suggest that dyspepsia may be concurrent with gastroesophageal reflux disease (GERD) (Schmulson, 2018).
Because the cause of FD is poorly understood, effective interventions are controversial. Although gastric acid secretion is often normal in patients with FD, treatment has historically focused on medications which at least partially affect acid secretion such as H2 antagonists, anticholinergics, and proton pump inhibitors (PPIs).
PPIs are commonly prescribed for the treatment of dyspeptic symptoms due to their success in the suppression of gastric acid in patients with GERD and peptic ulcers. PPIs have also been implicated as a successful intervention in raising gastric pH values in patients with Helicobacter pylori. Perhaps PPIs would be superior to H2 antagonists and prokinetics in the treatment of FD.
Objective(s)
This review was undertaken to establish the efficacy of PPIs when compared with placebo, H2 antagonists, and prokinetics in patients with FD. Ideally, a safety profile of the PPIs will also emerge.
Intervention/Methods
The authors of this review extensively searched a variety of electronic databases including Medline, Embase, and the Cochrane Library from 1946 to 2017. Non-English language trials were translated for inclusion and data were extracted through experienced translators.
The review assessed randomized controlled trials involving patients with a diagnosis of FD based on Rome criteria. Trials were included if any oral dose of PPI was compared with placebo, H2 antagonist, or prokinetic, or combination thereof, for at least 2 weeks' duration. Using the PICO (population, intervention, control, and outcomes) question format, data were gathered involving population characteristics, interventions, outcomes, and adverse events (diarrhea, intolerance, nausea, and headaches).
Study participants were all older than 16 years with a diagnosis of FD, regardless of gender. All participants had upper gastrointestinal pain but with normal upper endoscopy results. Participants with other gastrointestinal diagnosis such as peptic ulcer disease or GERD were excluded.
Results
Of the 25 studies included in this review, 18 studies encompassing 6,172 participants compared PPI therapy with placebo. PPI therapy was more effective than placebo (31.1% vs. 25.8%) in eliminating symptoms of FD with no increase in adverse effects. A subgroup analysis of the length of PPI treatment demonstrated a decreasing effectiveness from the 2-week treatment mark (risk ratio [RR] 0.78) to the 8-week treatment mark (RR 0.92). No quality-of-life improvements were noted.
Two trials including 740 participants evaluated the effects of PPI against H2 antagonists. No statistical improvement of dyspeptic symptoms between the two drug therapies was noted.
Five studies of 1,033 participants compared the effects of PPI to patients treated with prokinetics. A number needed to treat of 16 demonstrated only a small advantage of PPI over a prokinetic. Although all five studies documented adverse effects in both groups, no differences were observed in the frequency of their occurrence. Two of the included studies compared patients being treated with PPI and prokinetic against prokinetics alone. No statistically significant improvement in symptoms was demonstrated with combination therapy.
Conclusions
This review demonstrated statistical improvement of FD with the use of PPIs when compared with placebo with no increase in adverse effects. However, clinical significance is likely insufficient due to substantial heterogeneity between studies and no improvement in subjective quality of life. PPIs compared with H2 antagonists and prokinetics suggested little to no improvement in dyspeptic symptoms. These studies had small effect size and/or bias, which led the authors to be less confident in the reported results. Based on this review, no recommendations can be made for treatment of FD.
Implications
PPIs appear more effective for the treatment of FD when compared with placebo. However, these effects are short lived as the improvement is nearly ineffectual by 8 weeks of treatment (RR 0.92).
The successful treatment of FD evades a consistent algorithm for providers. Until future studies provide evidenced-based recommendations, the treatment of FD will be an individualized process.
REFERENCE