What medications are used to treat Irritable Bowel Syndrome (IBS)?

Medication for IBS

Start with symptom-specific first-line medications: loperamide 4-12 mg daily for diarrhea, soluble fiber (ispaghula/psyllium) 3-4 g/day for constipation, and antispasmodics (dicyclomine) for abdominal pain, then escalate to tricyclic antidepressants (amitriptyline 10 mg at bedtime, titrating to 30-50 mg) as second-line therapy for persistent symptoms after 3 months. 1, 2

First-Line Pharmacological Treatment (Symptom-Directed)

For Diarrhea-Predominant IBS (IBS-D)

• Loperamide is the most effective first-line agent, dosed at 4-12 mg daily either regularly or prophylactically (e.g., before going out) to reduce stool frequency, urgency, and fecal soiling 1, 2, 3
• Titrate the dose carefully as abdominal pain, bloating, nausea, and constipation are common side effects that may limit tolerability 1, 3
• Codeine 30-60 mg 1-3 times daily can be tried if loperamide fails, but CNS effects (sedation, dependency risk) are often unacceptable 1, 3
• Cholestyramine may specifically benefit a small subset of patients with bile salt malabsorption (approximately 10% of IBS-D patients), particularly those with <5% retention on SeHCAT testing, but is often less well tolerated than loperamide 1, 3

For Abdominal Pain and Cramping

• Antispasmodics with anticholinergic properties (dicyclomine, mebeverine) are first-line for abdominal pain, particularly when symptoms are meal-related 1, 2
• Common side effects include dry mouth, visual disturbance, and dizziness 1, 2
• Peppermint oil is an alternative antispasmodic option with fewer anticholinergic side effects 1

For Constipation-Predominant IBS (IBS-C)

• Start with soluble fiber (ispaghula/psyllium) at 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 2
• Polyethylene glycol (osmotic laxative) is reasonable as first-line therapy if fiber supplementation is insufficient, titrating the dose according to symptoms 1, 2
• Stimulant laxatives (senna) can be used but evidence for efficacy specifically in IBS-C is very limited 1

Probiotics as Adjunctive First-Line Therapy

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

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

For Persistent Abdominal Pain and Global Symptoms

• Tricyclic antidepressants (TCAs) are the most effective second-line treatment for global symptoms and abdominal pain, with strong evidence supporting their use 1, 2
• Start amitriptyline at 10 mg once daily at bedtime and titrate slowly to a maximum of 30-50 mg once daily 1, 2
• Provide careful explanation that these are used as gut-brain neuromodulators, not for depression, to ensure patient acceptance 1, 2
• Common side effects include dry mouth, drowsiness, and constipation (which may limit use in IBS-C) 1
• Selective serotonin reuptake inhibitors (SSRIs) may be an alternative if TCAs are not tolerated, but evidence is weaker 1, 2, 3

For IBS-D Refractory to Loperamide

• 5-HT3 receptor antagonists are the most efficacious drug class for IBS-D, though availability varies by country 1
• Ondansetron titrated from 4 mg once daily to a maximum of 8 mg three times daily is a reasonable alternative where alosetron and ramosetron are unavailable 1
• Constipation is the most common side effect 1, 3, 4
• Alosetron is FDA-approved only for women with severe IBS-D due to rare but serious risks of ischemic colitis and complications of constipation; it requires enrollment in a risk management program 4, 5
• Rifaximin (non-absorbable antibiotic) is efficacious for IBS-D in secondary care, though its effect on abdominal pain is limited 1, 5
• Eluxadoline (mixed opioid receptor drug) is efficacious for IBS-D but is contraindicated in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment 1, 5

For IBS-C Refractory to Fiber and Osmotic Laxatives

• Linaclotide (guanylate cyclase-C agonist) is the most efficacious secretagogue available for IBS-C, with strong evidence for improving both constipation and abdominal pain 1, 2
• Diarrhea is a common side effect 1, 2
• Lubiprostone (chloride channel activator) is an alternative secretagogue that is less likely to cause diarrhea than linaclotide, but nausea is a frequent side effect 1, 6
• The recommended dose for IBS-C is 8 mcg twice daily with food and water; capsules must be swallowed whole 6
• Plecanatide (another guanylate cyclase-C agonist) is also efficacious but diarrhea is no less likely than with linaclotide 1

Critical Treatment Principles

Dosing and Duration

• Review treatment efficacy after 3 months and discontinue if no response 2, 3
• For TCAs, continue for at least 6 months in those who respond to treatment 1
• Physicians and patients should periodically assess the need for continued therapy 6

Common Pitfalls to Avoid

• Do not use opioids for chronic abdominal pain management due to risks of dependence and complications 2
• Avoid extensive testing once IBS diagnosis is established 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
• Do not prescribe insoluble fiber (wheat bran) as it worsens bloating 2
• Avoid lubiprostone in patients with severe diarrhea or known/suspected mechanical gastrointestinal obstruction 6

Managing Expectations

• Complete symptom resolution is often not achievable; set realistic expectations with patients 1
• IBS has a benign but relapsing/remitting course requiring periodic adjustment of treatment strategy 1, 2, 3
• The efficacy of all drugs for IBS is modest, including newer agents developed specifically for IBS 1

Escalation to Psychological Therapies

• Refer for IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy when symptoms persist despite 12 months of pharmacological treatment 1, 2
• Consider earlier referral for patients who relate symptom exacerbations to stressors or have associated anxiety/depression 1