A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea

Abstract

BackgroundIrritable bowel syndrome with diarrhoea (IBS-D) is particularly debilitating due to urgency and episodic incontinence. Some 5-hydroxytryptamine 3 (5-HT3) receptor antagonists (5-HT3RAs) have proven effective but have serious side effects. Ondansetron, also a 5-HT3RA, has been widely used as an antiemetic with an excellent safety record for over two decades. Our aim was to assess its effectiveness in IBS-D.Methods120 patients meeting Rome III criteria for IBS-D entered a randomised, double-blind, placebo-controlled crossover study of 5 weeks of ondansetron 4 mg versus placebo with dose titration allowed, up to two tablets three times daily in the first 3 weeks. Patients completed daily diaries documenting stool consistency using the Bristol Stool Form score. Gut transit was measured in the last week of each treatment. The primary endpoint was average stool consistency in the last 2 weeks of treatment.ResultsOndansetron significantly improved stool consistency (mean difference in stool form between ondansetron and placebo −0.9, 95% CI −1.1 to −0.6, p<0.001). Compared with placebo, patients on ondansetron experienced fewer days with urgency (p<0.001), lower urgency scores (p<0.001), reduced frequency of defaecation (p=0.002) and less bloating (p=0.002), although pain scores did not change significantly. IBS symptom severity score fell more with ondansetron than placebo (83±9.8 vs 37±9.7, p=0.001). 65% reported adequate relief with ondansetron but not placebo compared with 14% reporting relief with placebo but not ondansetron, relative risk 4.7, 95% CI 2.6 to 8.5, p<0.001.ConclusionsOndansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.

Efficacy and Safety of 5-Hydroxytryptamine 3 Receptor Antagonists in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Garsed et al showed that ondansetron can achieve useful results with a low incidence of adverse effects. While their small study cannot prove the safety of ondansetron, the fact that it has been used widely for over 25 years without a single report of ischemic colitis suggests that this adverse effect is rare [12]. For the outcome rate of constipation, ramosetron had a lower pooled RR than the other comparisons between treatment and control groups.…”

“…The 21 RCTs involved 10,898 patients with IBS defined according to the Rome criteria: six investigated ramosetron [9,[20][21][22][23][24], 10 assessed alosetron [25][26][27][28][29][30][31][32][33][34], and two compared ondansetron [12,35] with placebo or mebeverine; these studies all scored !4 on the Jadad scale. However, the three cilansetron studies had Jadad scores of 3 [36-38].…”

“…Ondansetron inhibits the nausea and vomiting associated with chemotherapy. A recent study discovered that compared with placebo, patients given ondansetron experienced fewer days with urgency, lower urgency scores, reduced frequency of defecation, and less bloating [12]. These effects developed rapidly within 7 days; <10% of patients had constipation, and there were no cases of ischemic colitis.…”

“…This is the first time our study accepted the outcome "relief of abnormal bowel habits or stool consistency" as an endpoint for evaluating 5-HT 3 receptor antagonist efficacy for treating IBS. We included two studies on ondansetron that only included the endpoint "abnormal bowel habits or stool consistency improving" [12,35]; previous studies have not included this drug. However, the included studies used inconsistent assessment criteria.…”

Therapeutic strategies for functional dyspepsia and irritable bowel syndrome based on pathophysiology

“…5-HT 3 antagonists slow intestinal transit and improve diarrhoea and urgency in IBS. Ondansetron failed to improve abdominal pain [125] but alosetron, available in the USA, improves IBS symptoms, including pain, with an NNT of 8 [56]. Alosetron can cause ischaemic colitis, and although there are positive trial data in males, alosetron is only approved by the FDA for women with severe diarrhoea-predominant IBS [56].…”