What medications are recommended for a patient with Irritable Bowel Syndrome (IBS)?

Medications for Irritable Bowel Syndrome

Treatment Algorithm by IBS Subtype

Start with tricyclic antidepressants (amitriptyline 10 mg at bedtime, titrating to 30-50 mg) as the most effective first-line pharmacological treatment for IBS-M (mixed type), while using symptom-specific agents for IBS-D (diarrhea-predominant) and IBS-C (constipation-predominant) subtypes. 1, 2, 3, 4

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First-Line Pharmacological Treatments

For IBS-M (Mixed Symptoms)

• Tricyclic antidepressants are the most effective first-line drug for mixed IBS because they address both abdominal pain and alternating bowel patterns through gut-brain neuromodulation 1, 4
• Start amitriptyline 10 mg once daily at bedtime and titrate slowly to 30-50 mg once daily 1, 2, 3, 4
• Provide clear explanation that TCAs are used as gut-brain neuromodulators for pain modulation, not for depression—this counseling is critical for patient adherence 1, 2, 3, 4
• Common side effects include constipation (which may be less problematic than with older agents), dry mouth, and sedation 1

For IBS-D (Diarrhea-Predominant)

• Loperamide 4-12 mg daily is first-line therapy to reduce stool frequency, urgency, and fecal soiling 1, 2, 3
• Use either divided doses or a single 4 mg dose at night; many patients learn to use it prophylactically before going out 1
• Titrate the dose carefully as abdominal pain, bloating, nausea, and constipation are common and may limit tolerability 1, 3
• Antispasmodics (dicyclomine) are effective for abdominal pain, particularly when symptoms are meal-related 1, 2, 3
• Common side effects include dry mouth, visual disturbance, and dizziness 1, 3

For IBS-C (Constipation-Predominant)

• Start with soluble fiber (ispaghula/psyllium) 3-4 g/day, building up gradually to avoid bloating 1, 2, 3
• Avoid insoluble fiber (wheat bran) as it consistently worsens symptoms, particularly bloating 1, 2, 3
• If fiber supplementation is insufficient, add polyethylene glycol (osmotic laxative), titrating the dose according to symptoms 3

For Abdominal Pain (All Subtypes)

• Antispasmodics with anticholinergic properties (dicyclomine) are first-line for abdominal pain, especially when meal-related 1, 2, 3, 4
• Peppermint oil may be useful as an alternative antispasmodic, though evidence is more limited 2, 4

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Second-Line Pharmacological Treatments (For Refractory Symptoms After 3 Months)

For IBS-D Refractory to Loperamide

• 5-HT3 receptor antagonists (ondansetron) are likely the most efficacious drug class for IBS-D 1

• Start ondansetron 4 mg once daily and titrate to maximum 8 mg three times daily 1, 3

• Constipation is the most common side effect 1, 3

• Alosetron and ramosetron are unavailable in many countries; ondansetron is a reasonable alternative 1

• Rifaximin is efficacious for IBS-D but its effect on abdominal pain is limited 1

• Licensed for IBS-D in the USA but not available for this indication in many countries 1

• Rifaximin is a non-absorbable antibiotic with minimal systemic exposure 5

• Eluxadoline (mixed opioid receptor drug) is efficacious for IBS-D 1

• Contraindicated in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment 1

For IBS-C Refractory to Fiber and Osmotic Laxatives

• Linaclotide (guanylate cyclase-C agonist) is likely the most efficacious secretagogue available for IBS-C 1, 3

• Diarrhea is a common side effect 1, 3

• Lubiprostone (chloride channel activator) is efficacious for IBS-C 1

• Recommended dosage is 8 mcg twice daily for IBS-C in women at least 18 years old 6

• Take with food and water; swallow capsules whole 6

• Nausea is a frequent side effect; concomitant administration with food may reduce nausea 6

• Less likely to cause diarrhea than other secretagogues 1

• Plecanatide (another guanylate cyclase-C agonist) is efficacious for IBS-C, though diarrhea is common and no less likely than with linaclotide 1

For Persistent Global Symptoms

• Selective serotonin reuptake inhibitors (SSRIs) may be effective as second-line gut-brain neuromodulators for global symptoms 1, 3
• Provide careful explanation about rationale for use and counsel about side-effect profile 1, 3

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Adjunctive Therapies

Probiotics

• Trial probiotics for 12 weeks for global symptoms and abdominal pain—no specific species or strain can be recommended 1, 2, 3, 4
• Discontinue if no improvement after 12 weeks 1, 3, 4

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Critical Pitfalls to Avoid

• Do not use codeine routinely (15-30 mg, 1-3 times daily) as it is more likely to cause sedation and drug dependency compared to loperamide 1
• Avoid opioids for chronic abdominal pain management due to risks of dependence and complications 3, 4
• Do not pursue colonoscopy or extensive testing in patients under 45 without alarm features (unintentional weight loss ≥5%, blood in stool, fever, anemia, family history of colon cancer or inflammatory bowel disease) 2, 3, 4
• Avoid IgG-based food allergy testing as true food allergy is rare in IBS 2, 4
• Cholestyramine is only effective in the ~10% of IBS-D patients with documented bile salt malabsorption (75SeHCAT retention <5%); tolerability is poor and loperamide is equally effective 1

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Treatment Monitoring

• Review treatment efficacy after 3 months and discontinue ineffective medications 3, 4
• Physicians and patients should periodically assess the need for continued therapy 6
• For patients on lubiprostone, be aware that syncope and hypotension have been reported, particularly within an hour after the first dose or subsequent doses; most cases occurred with the 24 mcg twice daily dose (used for chronic idiopathic constipation, not IBS-C) 6

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When to Refer for Psychological Therapies

• Refer for IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy when symptoms persist despite pharmacological treatment for 12 months 2, 3, 4
• Consider earlier referral for patients who relate symptom exacerbations to stressors or have associated anxiety/depression 3