What are the treatment options for Irritable Bowel Syndrome with Diarrhea (IBS-D)?

Treatment of IBS-D

Start with lifestyle modifications and loperamide as first-line therapy, then escalate to tricyclic antidepressants if inadequate response, and finally consider FDA-approved medications (rifaximin, eluxadoline, or 5-HT3 antagonists) for persistent symptoms. 1, 2

First-Line Approach

Lifestyle Modifications

• Advise regular exercise for all IBS-D patients as it directly improves diarrhea symptoms. 1, 2, 3
• Recommend stress reduction techniques to address gut-brain axis dysfunction. 2

Dietary Interventions

• Start soluble fiber (ispaghula) at 3-4 g/day and gradually increase to avoid bloating—this improves global symptoms and abdominal pain. 1, 2, 3
• Avoid insoluble fiber (wheat bran) as it worsens IBS-D symptoms. 1, 2
• Consider a 12-week trial of probiotics for global symptoms and abdominal pain, though no specific strain can be recommended. 2, 3

Antidiarrheal Medication

• Loperamide is the recommended first-line pharmacologic treatment for diarrhea control—titrate carefully to minimize side effects including abdominal pain, bloating, nausea, and constipation. 1, 2, 3

Optional First-Line Additions

• Antispasmodics may help with abdominal pain and bloating, though side effects include dry mouth, visual disturbance, and dizziness. 3
• Peppermint oil can be considered for abdominal pain. 2

Second-Line Therapy (If Inadequate Response After 4-12 Weeks)

For Predominant Abdominal Pain and Global Symptoms

• Tricyclic antidepressants (TCAs) are strongly recommended as the most effective second-line therapy—start amitriptyline 10 mg once daily and titrate slowly to 30-50 mg once daily. 1, 2, 3
• SSRIs may be effective for global symptoms, particularly when comorbid anxiety or depression is present. 1, 3

For Predominant Diarrhea

• 5-HT3 receptor antagonists are likely the most efficacious drug class for IBS-D—ondansetron 4 mg once daily, titrated to maximum 8 mg three times daily, is a reasonable option. 1, 2, 3
• Monitor closely for constipation, the most common side effect of 5-HT3 antagonists. 1, 2
• Alosetron is effective but restricted to women with severe IBS-D refractory to other treatments under a risk management program due to rare ischemic colitis risk. 3

FDA-Approved Medications

Rifaximin (550 mg three times daily for 14 days):

• Effective for global symptoms and stool consistency. 1, 4
• Has the most favorable safety profile among FDA-approved agents. 5, 6
• Patients with symptom recurrence can be retreated up to two times with the same regimen. 4

Eluxadoline (100 mg twice daily):

• Mixed opioid receptor drug FDA-approved for IBS-D in adults. 1, 7
• Absolutely contraindicated in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment. 1, 2, 3, 7
• Common side effects include constipation, nausea, and headache. 2

Advanced Dietary Therapy

• Low FODMAP diet is effective as second-line dietary therapy for global symptoms and abdominal pain—must be supervised by a trained dietitian with systematic reintroduction of FODMAPs according to tolerance. 1, 2, 3
• Do not recommend gluten-free diets or IgG antibody-based food elimination diets specifically for IBS. 3

Special Considerations

Bile Acid Malabsorption

• Consider testing for bile acid malabsorption in patients with refractory IBS-D symptoms, especially those with prior cholecystectomy. 2
• Bile acid sequestrants (cholestyramine) may be effective in these patients. 3

Psychological Comorbidities

• Psychological therapies (cognitive behavioral therapy, hypnotherapy, mindfulness-based stress reduction) should be considered when symptoms are refractory to pharmacological treatments, particularly with psychological comorbidities. 1, 3

Critical Pitfalls to Avoid

• Never use eluxadoline in patients with cholecystectomy—this is an absolute contraindication due to sphincter of Oddi dysfunction risk. 1, 2, 3
• Discontinue rifaximin if diarrhea worsens or persists beyond 24-48 hours—consider alternative pathogens beyond E. coli. 4
• Monitor for Clostridium difficile-associated diarrhea with rifaximin use, though risk is low. 4
• Watch for constipation development with 5-HT3 antagonists and eluxadoline—this is the most common side effect requiring dose adjustment. 1, 2
• Be aware of ischemic colitis risk with alosetron, which is why it requires restricted prescribing. 2, 3