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

Background Irritable 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. Methods 120 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. Results Ondansetron 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. Conclusions Ondansetron relieves some of the most intrusive symptoms of IBS-D, namely loose stools, frequency and urgency.

• Publication year

  2013

• Venue

  Gut

• Publication date

  2013-12-12

• Fields of study

  Medicine

• Identifiers
  DOI 10.1136/gutjnl-2013-305989PMID 24334242PMCID 4173656
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS

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• Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation.

  2011cited by this paper
• The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome.

  2011cited by this paper
• Serotonin signaling is altered in irritable bowel syndrome with diarrhea but not in functional dyspepsia in pediatric age patients.

  2010cited by this paper
• Postprandial changes in small bowel water content in healthy subjects and patients with irritable bowel syndrome.

  2010cited by this paper
• Ischemic Colitis and Complications of Constipation Associated With the Use of Alosetron Under a Risk Management Plan: Clinical Characteristics, Outcomes, and Incidences

  2010cited by this paper
• Postinfectious irritable bowel syndrome.

  2009cited by this paper
• CENTER FOR DRUG EVALUATION AND RESEARCH

  2009cited by this paper
• Predictors of Patient-Assessed Illness Severity in Irritable Bowel Syndrome

  2008cited by this paper
• A Phase II Trial of the Novel Serotonin Type 3 Receptor Antagonist Ramosetron in Japanese Male and Female Patients with Diarrhea-Predominant Irritable Bowel Syndrome

  2008cited by this paper
• Effects of 5-hydroxytryptamine (serotonin) type 3 antagonists on symptom relief and constipation in nonconstipated irritable bowel syndrome: a systematic review and meta-analysis of randomized controlled trials.

  2008cited by this paper
• Postinfectious irritable bowel syndrome.

  2008cited by this paper
• A randomized, double-blind, placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome

  2008cited by this paper
• Afferent hypersensitivity in a mouse model of post‐inflammatory gut dysfunction: role of altered serotonin metabolism

  2008cited by this paper
• A Randomized, Double-Blind, Placebo-Controlled Study to Assess Efficacy and Safety of 0.5 mg and 1 mg Alosetron in Women With Severe Diarrhea-predominant IBS

  2007cited by this paper
• FUNCTIONAL BOWEL DISORDERS

  2007cited by this paper
• Evaluation of the pharmacological profile of ramosetron, a novel therapeutic agent for irritable bowel syndrome.

  2007cited by this paper
• Incidence of Ischemic Colitis and Serious Complications of Constipation Among Patients Using Alosetron: Systematic Review of Clinical Trials and Post-Marketing Surveillance Data

  2006cited by this paper
• Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome.

  2005cited by this paper
• Characterization of the Alternating Bowel Habit Subtype in Patients with Irritable Bowel Syndrome

  2005cited by this paper
• Clinical determinants of health-related quality of life in patients with irritable bowel syndrome.

  2004cited by this paper
• Review article: serotonin receptors and transporters — roles in normal and abnormal gastrointestinal motility

  2004cited by this paper
• Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS.

  2003cited by this paper
• An irritable bowel syndrome-specific symptom questionnaire: development and validation.

  2003cited by this paper
• Efficacy of alosetron in irritable bowel syndrome: a meta‐analysis of randomized controlled trials

  2003cited by this paper
• The PHQ-15: Validity of a New Measure for Evaluating the Severity of Somatic Symptoms

  2002cited by this paper
• Patient satisfaction with alosetron for the treatment of women with diarrhea-predominant irritable bowel syndrome

  2002cited by this paper
• Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome.

  2002cited by this paper
• Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat

  2001cited by this paper
• The 5-HT3 receptor antagonist alosetron inhibits the colorectal distention induced depressor response and spinalc-fos expression in the anaesthetised rat

  2000cited by this paper
• Preclinical and clinical pharmacology of the 5-HT3 receptor antagonists

  2000cited by this paper
• Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acuteCampylobacter enteritis and in post-dysenteric irritable bowel syndrome

  2000cited by this paper
• The pharmacological properties of the novel selective 5‐HT3 receptor antagonist, alosetron, and its effects on normal and perturbed small intestinal transit in the fasted rat

  1999cited by this paper
• The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress

  1997cited by this paper
• Evaluation of a new quality of life questionnaire for patients with irritable bowel syndrome

  1997cited by this paper
• Selective 5‐hydroxytryptamine antagonism: a role in irritable bowel syndrome and functional dyspepsia?

  1996cited by this paper
• A 5HT3 antagonist corrects the postprandial colonic hypertonic response in carcinoid diarrhea.

  1994cited by this paper
• An office guide to whole-gut transit time. Patients' recollection of their stool form.

  1994cited by this paper
• Development of the Perceived Stress Questionnaire: a new tool for psychosomatic research.

  1993cited by this paper
• GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man

  1990cited by this paper
• Simplified assessment of segmental colonic transit.

  1987cited by this paper

• Glucocorticoid signaling mitigates colitis-associated visceral hypersensitivity by suppressing 5-HT release in enterochromaffin cells via a GR-PI3K-SGK1 axis.

  2026cites this paper
• Morbidity and Mortality of Ondansetron in Patients with Non-congenital Long QT Syndrome: A Review Article.

  2025cites this paper
• Major Adverse Cardiac Events with Ondansetron: A Systematic Review.

  2025cites this paper
• Rome Foundation Working Team Report on overlap in disorders of gut–brain interaction

  2025cites this paper
• Pharmacologic treatment of irritable bowel syndrome. Position statement of the Asociación Mexicana de Gastroenterología, 2024.

  2025cites this paper
• [Treatment of Irritable Bowel Syndrome with Predominant Diarrhea].

  2025cites this paper
• The impact of ondansetron on clinical outcomes in cranial surgery patients: a propensity-matched analysis of retrospective data

  2025cites this paper
• Assessing Water Content of the Human Colonic Chyme Using the MRI Parameter T1: A Key Biomarker of Colonic Function

  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2025cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023influential citation
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
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  2022cites this paper
• Adult enteric Dclk1-positive glial and neuronal cells reveal distinct responses to acute intestinal injury.

  2022cites this paper
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  2022cites this paper
• The serotonin receptor 3E variant is a risk factor for female IBS-D

  2022cites this paper
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  2022cites this paper
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  2022cites this paper
• Comparison of five diarrhea-predominant irritable bowel syndrome (IBS-D) rat models in the brain-gut-microbiota axis.

  2022cites this paper
• Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study

  2022cites this paper
• Diarrhea-Predominant and Constipation-Predominant Irritable Bowel Syndrome: Current Prescription Drug Treatment Options

  2021cites this paper
• Designing New Foods or Food Ingredients Targeting the Gut Microbiota to Reduce FODMAP-Induced Irritable Bowel Syndrome (IBS)

  2021cites this paper
• Small bowel water content assessed by MRI in health and disease: a collation of single‐centre studies

  2021cites this paper
• Improvement in constipation and diarrhea is associated with improved abdominal pain in patients with functional bowel disorders

  2021cites this paper
• Medical Therapies for Diarrhea-Predominant Irritable Bowel Syndrome.

  2021cites this paper
• The alternative serotonin transporter promoter P2 impacts gene function in females with irritable bowel syndrome

  2021cites this paper
• Comparative effectiveness of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: a network meta-analysis of randomized controlled studies

  2021influential citation
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  2021cites this paper
• Psychopharmacologic Therapies for Irritable Bowel Syndrome.

  2021cites this paper
• Pharmacological Therapies and Their Clinical Targets in Irritable Bowel Syndrome With Diarrhea

  2021cites this paper
• Atractylodes oil alleviates diarrhea-predominant irritable bowel syndrome by regulating intestinal inflammation and intestinal barrier via SCF/c-kit and MLCK/MLC2 pathways.

  2021cites this paper
• Evidence-based clinical practice guidelines for irritable bowel syndrome 2020

  2021cites this paper
• Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine

  2021cites this paper
• Irritable Bowel Syndrome in Pregnancy.

  2021cites this paper
• Management of functional gastrointestinal disorders.

  2021cites this paper
• Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders.

  2021cites this paper
• Update S3-Leitlinie Reizdarmsyndrom: Definition, Pathophysiologie, Diagnostik und Therapie. Gemeinsame Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Neurogastroenterologie und Motilität (DGNM) – Juni 2021

  2021cites this paper
• British Society of Gastroenterology guidelines on the management of irritable bowel syndrome

  2021cites this paper
• Review article: current and future treatment approaches for pain in IBS

  2021cites this paper
• Does Intravenous Ondansetron Affect the Intestinal Motility Pattern in Healthy Donkeys (Equus asinus)?

  2021cites this paper
• Review Article: Current and future treatment approaches for IBS with diarrhoea (IBS‐D) and IBS mixed pattern (IBS‐M)

  2021cites this paper
• Re: Comments by Profs. Black and Ford Regarding Plasse et al., Bimodal Ondansetron in IBS-D.

  2020cites this paper
• Recent advances in diagnosis and management of irritable bowel syndrome.

  2020cites this paper
• Irritable bowel syndrome with diarrhea: Treatment is a work in progress.

  2020cites this paper
• Best management of irritable bowel syndrome

  2020cites this paper
• An update on efficacy and safety considerations for the latest drugs used to treat irritable bowel syndrome

  2020cites this paper
• Functional diarrhea

  2020cites this paper
• Pharmacokinetic profile of the selective 5-HT3 receptor antagonist ondansetron in the rat: an original study and a mini-review of the behavioural pharmacological literature in the rat.

  2020cites this paper
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  2020cites this paper
• A short course of oral ranitidine as a novel treatment for toddler’s diarrhea: a parallel-group randomized controlled trial

  2020cites this paper
• Vortioxetine effects on quality of life of irritable bowel syndrome patients: A randomized, double‐blind, placebo‐controlled trial

  2020cites this paper
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  2020cites this paper