What medications are recommended for irritable bowel syndrome (IBS)?

Medication Management for Irritable Bowel Syndrome

The optimal medication strategy for IBS depends on the predominant bowel pattern: for IBS with diarrhea (IBS-D), 5-HT3 receptor antagonists (particularly ondansetron) are the most efficacious class, while for IBS with constipation (IBS-C), linaclotide is the most effective secretagogue, and tricyclic antidepressants (TCAs) starting at 10 mg amitriptyline are the strongest evidence-based treatment for global symptoms and abdominal pain across all IBS subtypes. 1

First-Line Pharmacological Approach

For All IBS Subtypes (Global Symptoms and Pain):

• Start with tricyclic antidepressants (TCAs) as the most effective treatment for global symptoms and abdominal pain. Begin with amitriptyline 10 mg once daily at bedtime and titrate slowly to 30-50 mg once daily. 1, 2 This carries a strong recommendation with moderate quality evidence. 1

• Clearly explain to patients that TCAs are being used for gut-brain neuromodulation and visceral pain control, not for depression, to improve adherence and reduce stigma. 1, 2

• Antispasmodics (such as dicyclomine) may be used for intermittent symptom relief, though they are less effective than TCAs and have common anticholinergic side effects including dry mouth, visual disturbance, and dizziness. 1, 2 These carry weak recommendations due to very low quality evidence. 1

• Peppermint oil effectively treats global symptoms and abdominal pain, with gastroesophageal reflux being the main side effect. 2

For IBS with Diarrhea (IBS-D):

First-line:

• Loperamide 4-12 mg daily effectively controls stool frequency and urgency but has minimal effect on abdominal pain. 2, 3

Second-line (most efficacious):

• 5-HT3 receptor antagonists are the most efficacious drug class for IBS-D. 1 Ondansetron should be titrated from 4 mg once daily to a maximum of 8 mg three times daily. 1, 2 Constipation is the most common side effect. 1

• Rifaximin 550 mg three times daily for 14 days is an efficacious second-line option with the most favorable safety profile, though its effect on abdominal pain is limited. 1, 4 It can be repeated as needed for symptom recurrence. 4

• Eluxadoline (mixed opioid receptor drug) is efficacious but has absolute contraindications in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment. 1, 4

For IBS with Constipation (IBS-C):

Second-line secretagogues (after laxatives fail):

• Linaclotide 290 mcg once daily is the most efficacious secretagogue for IBS-C (strong recommendation, high quality evidence). 1 Diarrhea is a common side effect. 1

• Lubiprostone 8 mcg twice daily is less likely to cause diarrhea than other secretagogues but nausea is a frequent side effect (strong recommendation, moderate quality evidence). 1, 5 Take with food and water to reduce nausea. 5

• Tenapanor is efficacious with strong evidence (high quality), though diarrhea is frequent and availability is limited outside the USA. 1

• Plecanatide is another guanylate cyclase-C agonist option, though evidence quality is very low. 1

• Tegaserod (5-HT4 agonist) is efficacious but unavailable outside the USA. 1

Alternative Second-Line Options

• Selective serotonin reuptake inhibitors (SSRIs) may be effective for global symptoms when TCAs are not tolerated, though evidence quality is lower than for TCAs. 1, 2 Provide the same counseling about gut-brain modulation as with TCAs. 1

Treatment Algorithm

1. Start all patients on TCAs (amitriptyline 10 mg at bedtime) for global symptoms and pain, titrating to 30-50 mg daily. 1, 2

2. For IBS-D: Add ondansetron 4 mg once daily (titrate to 8 mg three times daily) if TCAs alone are insufficient. 1, 2 If refractory, consider rifaximin 550 mg three times daily for 14 days. 1

3. For IBS-C: If laxatives fail, escalate to linaclotide 290 mcg once daily as the most efficacious option. 1 If nausea is a concern, choose lubiprostone 8 mcg twice daily instead. 1

4. Review treatment efficacy after 3 months and discontinue ineffective therapies. 3

5. If symptoms persist after 12 months of drug treatment, consider psychological therapies (IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy). 1

Critical Pitfalls to Avoid

• Never use insoluble fiber (wheat bran) as it consistently exacerbates IBS symptoms, particularly IBS-D. 3

• Avoid eluxadoline in patients with cholecystectomy or sphincter of Oddi dysfunction due to risk of pancreatitis. 1, 4

• Do not combine TCAs with other serotonergic agents without vigilance for serotonin syndrome. 3

• Avoid antispasmodics in constipation-predominant IBS as anticholinergic effects worsen constipation. 2

• Do not use lubiprostone in patients with mechanical gastrointestinal obstruction. 5

• Monitor for syncope and hypotension with lubiprostone, particularly in the first hour after dosing and in patients taking blood pressure medications. 5

Comparative Efficacy Evidence

Network meta-analysis of 18 RCTs (9,844 patients) demonstrated that alosetron 1 mg twice daily ranked first for efficacy based on the FDA composite endpoint of improvement in both abdominal pain and stool consistency, though it is only available for women with severe refractory IBS-D in the USA. 6 Ramosetron 2.5 mcg once daily ranked first for abdominal pain relief, while rifaximin 550 mg three times daily ranked first for safety. 6