92,95,163–167 Six of the seven studies were conducted in Western populations and they demonstrated a benefit over placebo for symptom improvement in FD patients,92,163–167 though PPIs may not be effective in dysmotility-like dyspepsia.168 In fact, the combined effect of all seven trials (2387 PPI patients, 1338 placebo patients) was expressed in a recent meta-analysis,169 which reported that there was a modest but statistically significant difference in symptom relief in patients receiving PPIs (40.3%) compared with those given placebo (32.7%), and the estimated number needed to selleck chemical treat was 14.6 patients (95% CI, 8.7 to 57.1).

It must be noted that the only trial that showed negative results among the seven trials in the abovementioned meta-analysis was from Hong Kong. In addition, a recent randomized trial from Hong Kong that investigated the efficacy of a PPI on H. pylori-negative uninvestigated dyspeptic patients (epigastric pain and discomfort) also failed to show an efficacy of PPI over placebo.96 An open-labelled study from Singapore, also reported only a modest response to PPI.170 Characteristic differences between Asian and Western patients with FD may explain the lower benefit of PPIs in Asian patients. These data suggest that the efficacy of PPIs in patients with FD needs to be re-evaluated in the Asian population. Statement 25. High-dose

proton pump inhibitor therapy is not superior to standard doses for symptom control in functional Transmembrane Transporters modulator dyspepsia. Grade of evidence: moderate. Racecadotril Strength of recommendation: probably not do it. Level of agreement: a: 65.0%; b: 25.0%; c: 10.0%; d: 0%; e: 0%; f: 0%. Several studies have examined the role of standard and

higher doses of PPI in the treatment of FD.95,164–166,168 Whether the patients responded to PPIs or not, these studies, which involved a large number of patients, consistently found no difference in symptom response between standard and higher PPI doses. A recent meta-analysis also concluded that the dose of PPI did not influence the response of FD symptoms to treatment.169 It is therefore proposed that a standard dose of PPI is sufficient in the management of FD, and that dose escalation is unlikely to further reduce symptoms. Another concern regarding the use of higher doses of PPI in patients with FD relates to incurring unwanted problems caused by acid inhibition. Recent studies of healthy, asymptomatic volunteers who received PPI treatment for either 4 or 8 weeks demonstrated rebound acid hypersecretion following withdrawal of the PPI, resulting in the development of dyspeptic symptoms after PPI treatment.171,172 Yet another concern regarding PPI administration relates to the development of small intestinal bacterial overgrowth (SIBO) in patients receiving long-term therapy.173 Although long-term PPI therapy has not been advocated in FD, the risk of SIBO may be greater in patients on higher PPI doses than in patients on standard PPI doses.