Diarrhea-dominant irritable bowel syndrome (IBS-D) is a deliberating and chronic condition that can impair social activities. Determining proper medication with satisfactory outcomes has been a challenge. The 5-hydroxytryptamine 3 receptor antagonist (5-HT3 RA) drugs have demonstrated favorable outcomes on IBS-D in the last 3 decades. Ondansetron, also a 5-HT3 RA is known as an antiemetic. Our aim was to evaluate the efficacy of ondansetron in IBS-D. In this single-center, double-blind, randomized controlled trial, patients with IBS-D were recruited. Patients were randomized on a 1:1 ratio and assigned into two groups: imipramine 25 mg/daily plus ondansetron 4 mg/3 times per day and imipramine 25 mg/daily plus placebo. The primary endpoint was the frequency of diarrhea per day after 8 weeks of treatment. The secondary endpoints consisted of changes in the frequency of defecation urgency per day, the number of days with gastrointestinal pain and bloating, and the patients' overall satisfaction regarding bowel habits after 8 weeks of the treatment. Data from 98 patients were analyzed. Ondansetron, compared to placebo, improved the primary outcome, and the stool consistency was increased significantly (3.29±1.19 vs 4.55±1.17, P<0.001). Moreover, the response rate for the diarrhea frequency was significantly higher in the ondansetron group compared to the placebo (77.5% vs 34.7%, P<0.001). In the ondansetron group, fewer urgencies were experienced, and pain severity and feeling of bloating declined as well (P<0.01). Ondansetron can mitigate almost all IBS-D-related symptoms, which may indicate it as a drug of choice; however, further evidence is required to ascertain its safety.
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