In the Rome III classification, functional dyspepsia (FD) has been further subcategorized into two different syndromes, namely, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS). Acid-related pathophysiology seems to be mainly responsible for EPS, and antisecretory agents such as proton-pump inhibitors (PPIs) seem to be effective mainly against EPS. However, recent information as to the relationship between initial duodenal acid sensitization in the early postprandial phase and delayed gastric emptying in the later postprandial phase would suggest the amelioration of PDS by antisecretory agents. In the present review, we summarized the recent literature on the direct and indirect effect of PPIs in FD (including not only Rome III, but also Rome II criteria). The effects of PPIs against FD are heterogeneous, depending on the protocol of the clinical studies, and the inclusion criteria of each randomized controlled trial (primary care or tertiary care population). As the placebo effects cannot be ignored in this disease, a placebo-controlled study would be necessary, at least for the evaluation of the effect of each agent on symptom relief in patients with FD. Further studies directly comparing PPIs with suitable placebos in terms of their effects in reducing the symptoms of endoscopically confirmed, Rome III-based FD are awaited.
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