Efficacy of acotiamide in combination with esomeprazole for functional dyspepsia refractory to proton-pump inhibitor monotherapy

Functional dyspepsia (FD) is a gastroduodenal disorder that presents as postprandial fullness, early satiation, or epigastric burning despite no evidence of a structural disease. Proton pump inhibitors (PPIs) are often the first choice for treating FD. However, some patients need additional medication because of residual symptoms despite a certain level of benefit from the PPI. For these patients, a combination of PPI and other agents has a possibly more beneficial effect than changing their medication. This study aimed to evaluate the efficacy of an initial PPI followed by combination therapy with PPI and acotiamide in FD patients with residual symptoms after an initial PPI. We enrolled 105 patients who started an initial PPI (20 mg of esomeprazole once a day). Twenty-three patients with residual symptoms received 100 mg of acotiamide, a cholinesterase inhibitor, three times a day with esomeprazole as a combination therapy for 2 weeks. The symptoms were evaluated using the modified Frequency Scale for the Symptoms of Gastroesophageal Reflux Disease (mFSSG). Eighteen of 23 patients (78%) achieved an overall improvement in symptoms. Almost all FD-related symptoms statistically improved after the combination therapy, with an improvement in the mFSSG score relevant to the postprandial distress syndrome and epigastric pain syndrome. The symptoms improved regardless of age, sex, and the pre-combination therapy score of the mFSSG. Our findings suggest that the combination therapy of acotiamide and PPI may be effective in selected FD patients with insufficient improvement with an initial PPI. However, well-designed trials are required to confirm the efficacy.