What are the treatment options for Irritable Bowel Syndrome (IBS) with diarrhea?

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Last updated: March 28, 2025View editorial policy

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From the Guidelines

For irritable bowel syndrome with diarrhea (IBS-D), 5-Hydroxytryptamine 3 receptor antagonists, such as ondansetron, are a recommended second-line treatment option, as they are likely the most efficacious for IBS with diarrhea, according to the British Society of Gastroenterology guidelines 1.

Treatment Options

  • First-line treatments for IBS-D typically include dietary modifications (low-FODMAP diet), antispasmodics (like dicyclomine), and antidiarrheals (like loperamide) 1.
  • Second-line treatments may include tricyclic antidepressants, selective serotonin reuptake inhibitors, eluxadoline, and rifaximin, but their use should be carefully considered due to potential side effects and limited availability 1.
  • 5-Hydroxytryptamine 3 receptor antagonists, such as ondansetron, can be initiated in secondary care, with a starting dose of 4 mg once a day, titrated to a maximum of 8 mg three times a day, as they have been shown to be efficacious in reducing diarrhea in IBS-D patients 1.

Key Considerations

  • When considering second-line treatments, it is essential to weigh the potential benefits against the risks of side effects, such as constipation, nausea, and headache 1.
  • Patients should be counselled about the rationale for using these medications and the potential side effects, and regular follow-up is crucial to assess symptom improvement and manage any side effects 1.
  • The use of neuromodulators, such as tricyclic antidepressants and selective serotonin reuptake inhibitors, may also be considered, as they can act on pathways between the gut and the brain to improve symptoms, but their effects on IBS-D are not as well established as those of 5-Hydroxytryptamine 3 receptor antagonists 1.

From the FDA Drug Label

VIBERZI is indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D). VIBERZI is a mu-opioid receptor agonant, indicated in adults for the treatment of irritable bowel syndrome with diarrhea (IBS-D). (1)

The treatment option for Irritable Bowel Syndrome (IBS) with diarrhea is eluxadoline (VIBERZI), a mu-opioid receptor agonist 2 2.

From the Research

Treatment Options for Irritable Bowel Syndrome (IBS) with Diarrhea

  • Nonpharmacological interventions:
    • Dietary and lifestyle modification, which are generally used as first-line therapy 3
    • Probiotics have demonstrated efficacy and safety in patients with IBS, but studies are inconsistent in strains examined, dosing, and treatment duration 3
    • Psychological therapies (e.g. cognitive behavioral therapy, hypnotherapy) also may improve IBS symptoms 3, 4
  • Pharmacological interventions:
    • US Food and Drug Administration-approved agents: eluxadoline, rifaximin, and alosetron 3, 5
    • Loperamide, smooth muscle antispasmodics, bile acid sequestrants, and antidepressants (i.e. tricyclic antidepressants, selective serotonin reuptake inhibitors) 3, 4
    • Eluxadoline and rifaximin have been shown to improve abdominal pain and stool consistency in patients with IBS-D 3, 5
    • Alosetron improves IBS symptoms, but is approved only for women with severe IBS-D 3
    • Rifaximin has the most favorable safety profile among the three approved agents 3
    • Serotonin-3 receptor antagonists, eluxadoline and rifaximin are currently approved therapeutic options for patients with first-line refractory IBS-D 6

Alternative Therapeutic Approaches

  • Fecal microbiota transplantation and enterobacterial "crapsules" are being evaluated as novel therapeutic approaches for IBS-D and functional diarrhea 6
  • Drugs targeting bile acid synthesis and excretion may benefit patients with bile acid diarrhea 6
  • Further understanding of the underlying pathophysiology of IBS-D and functional diarrhea is needed to develop effective therapeutic approaches 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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