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

Treatment for IBS-D

Start with loperamide 4-12 mg daily as first-line pharmacological therapy for IBS-D, as it most effectively reduces stool frequency and urgency with the strongest evidence base. 1

Initial Management Approach

Lifestyle and Dietary Modifications

• Recommend regular exercise to all IBS-D patients as it provides significant symptom management benefits 1
• Identify and reduce excessive intake of lactose, fructose, sorbitol, caffeine, and alcohol, as these commonly trigger diarrhea 2, 1
• Trial lactose or fructose exclusion if dietary history suggests intolerance 2
• Consider a supervised low FODMAP diet trial with a trained dietitian for persistent symptoms, with planned reintroduction according to tolerance 1
• Avoid insoluble fiber (wheat bran) as it worsens symptoms; instead, use soluble fiber like ispaghula/psyllium starting at 3-4g/day and gradually increasing 1

Patient Education

• Explain IBS-D as a disorder of gut-brain interaction, emphasizing the brain-gut axis and how diet, stress, and emotional responses affect symptoms 2, 1
• Reassure patients about the benign prognosis and relapsing/remitting course 2
• Clarify that true food allergy is rare but food intolerance is common 2

First-Line Pharmacological Treatment

Antidiarrheal Agents

• Loperamide 4-12 mg daily (either regularly or prophylactically before going out) is the most effective first-line treatment for reducing stool frequency and urgency 2, 1
• Codeine 30-60 mg, 1-3 times daily can be tried if loperamide fails, but CNS effects (sedation, dependency) are often unacceptable 2, 1

Antispasmodics for Pain

• Anticholinergic antispasmodics (dicyclomine) show greater efficacy for abdominal pain relief than direct smooth muscle relaxants 1
• These agents are particularly effective when symptoms are meal-related 2

Bile Acid Malabsorption

• Approximately 10% of IBS-D patients have bile salt malabsorption and may respond to cholestyramine, particularly those with <5% retention on SeHCAT testing 1
• Cholestyramine is often less well tolerated than loperamide 2

Second-Line Pharmacological Treatment

Gut-Brain Neuromodulators

• Tricyclic antidepressants (TCAs) are highly effective for pain and global symptoms in IBS-D 1
• Start amitriptyline or trimipramine at 10 mg once daily, gradually titrating to 30-50 mg once daily 1
• TCAs are especially useful when insomnia is prominent, though they may aggravate constipation 2
• Continue for at least 6 months if the patient reports symptomatic response 2
• Selective serotonin reuptake inhibitors (SSRIs) may be considered if TCAs are not tolerated, though evidence is weaker 2, 1

FDA-Approved Medications for IBS-D

• Rifaximin (XIFAXAN): 550 mg three times daily for 14 days; patients can be retreated up to two times for symptom recurrence 3, 4
  • Works by modulating gut microbiota, reducing inflammation, normalizing visceral hypersensitivity, and decreasing intestinal permeability 4
  • Particularly effective for bloating, stool consistency, and abdominal pain 5
• Eluxadoline (VIBERZI): FDA-approved for IBS-D in adults, administered as chronic daily therapy 6, 4
  • Mixed µ- and κ-opioid receptor agonist/δ-opioid antagonist that decreases GI motility, fluid secretion, and visceral pain 4
• Alosetron: Selective 5-HT3 antagonist, but restricted to women with severe IBS-D refractory to conventional therapy due to safety concerns 5, 4

Probiotics

• May improve global symptoms and abdominal pain 1
• Recommend a 12-week trial and discontinue if no improvement 1
• No specific strain can be recommended based on current evidence 1

Psychological Therapies

• Consider IBS-specific cognitive behavioral therapy (CBT) or gut-directed hypnotherapy for symptoms refractory to pharmacological treatment for 12 months 2, 1
• Simple relaxation therapy using audiotapes may be beneficial as an initial approach 2, 1
• Biofeedback is especially helpful for disordered defecation 2
• Dynamic psychotherapy is useful for patients who relate symptom exacerbations to stressors or have associated anxiety/depression 2

Treatment Monitoring and Adjustment

• Review treatment efficacy after 3 months and discontinue ineffective medications 1
• Recognize that symptoms may relapse and remit over time, requiring periodic adjustment of treatment strategy 1
• Avoid extensive testing once IBS-D diagnosis is established 1

Important Caveats and Pitfalls

When to Reconsider Diagnosis

• Discontinue rifaximin if diarrhea symptoms worsen or persist more than 24-48 hours, and consider alternative antibiotic therapy 3
• Rifaximin is not effective for travelers' diarrhea due to Campylobacter jejuni, and effectiveness against Shigella and Salmonella is unproven 3
• Severe or refractory symptoms should prompt review of the diagnosis with consideration of further targeted investigation 2

Clostridium difficile Risk

• Be aware that Clostridium difficile-associated diarrhea (CDAD) has been reported with rifaximin use 3
• Consider CDAD in all patients who present with diarrhea following antibiotic use 3

Avoiding Harm

• Avoid opioid prescribing, unnecessary surgery, and unproven unregulated diagnostic or therapeutic approaches incentivized by financial or reputational gain 2
• For severe or refractory IBS-D, manage with an integrated multidisciplinary approach to reduce iatrogenic harms 2
• When using combination gut-brain neuromodulators (augmentation), maintain vigilance for risks of serotonin syndrome 2