Medications for Irritable Bowel Syndrome
Treatment Algorithm Based on IBS Subtype
The medication approach to IBS must be determined by the predominant bowel pattern (diarrhea, constipation, or mixed), with tricyclic antidepressants serving as the most effective second-line therapy across all subtypes for refractory abdominal pain. 1, 2
First-Line Medications by Subtype
IBS with Diarrhea (IBS-D)
Loperamide 4-12 mg daily is the most effective first-line medication for IBS-D, significantly reducing stool frequency and urgency. 2 Titrate the dose carefully to avoid constipation, abdominal pain, bloating, and nausea. 1
Antispasmodics with anticholinergic properties (dicyclomine) are effective for abdominal pain, particularly when symptoms worsen after meals. 2 Common side effects include dry mouth, visual disturbance, and dizziness. 1
Peppermint oil can be used as an alternative antispasmodic with sufficient evidence for symptom reduction. 3, 4
IBS with Constipation (IBS-C)
Soluble fiber (ispaghula/psyllium) 3-4 g/day should be started first, gradually increasing to avoid bloating. 1, 2 Avoid insoluble fiber (wheat bran) as it worsens symptoms. 3
Polyethylene glycol (osmotic laxative) should be titrated according to symptoms if fiber is insufficient, with abdominal pain being the most common side effect. 3
Do NOT use anticholinergic antispasmodics like dicyclomine in IBS-C as they reduce intestinal motility and worsen constipation. 3
IBS with Mixed Symptoms (IBS-M)
- Tricyclic antidepressants (amitriptyline 10 mg once daily) are the most effective first-line pharmacological treatment for IBS-M, starting low and titrating slowly to 30-50 mg once daily. 2, 5
Second-Line Medications
For All IBS Subtypes with Refractory Pain
Tricyclic antidepressants (TCAs) are the most effective second-line medication for global symptoms and abdominal pain across all IBS subtypes. 1, 2 Start amitriptyline 10 mg once daily at bedtime and titrate by 10 mg/week to 30-50 mg daily. 1, 3 Continue for at least 6 months if symptomatic response occurs. 1
Selective serotonin reuptake inhibitors (SSRIs) may be used if TCAs are not tolerated, though evidence is weaker. 1, 2 If concurrent mood disorder exists, SSRIs should be used instead of low-dose TCAs. 5
For IBS-D Refractory to Loperamide
5-HT3 receptor antagonists (ondansetron 4 mg once daily, titrated to maximum 8 mg three times daily) are the most efficacious drug class for IBS-D. 1, 2 Constipation is the most common side effect. 1
Rifaximin (non-absorbable antibiotic) 550 mg three times daily for 14 days is efficacious for IBS-D, though its effect on abdominal pain is limited. 1, 6 Licensed in the USA but unavailable in many countries. 1
Eluxadoline (mixed opioid receptor drug) is efficacious for IBS-D but 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 290 mcg once daily on an empty stomach is the most efficacious secretagogue for IBS-C, addressing both abdominal pain and constipation with high-quality evidence. 1, 3 Take at least 30 minutes before the first meal. 3 Diarrhea is the most common side effect. 1
Lubiprostone 8 mcg twice daily with food is an alternative secretagogue for women with IBS-C, less likely to cause diarrhea than linaclotide. 1, 7 Nausea is the most common side effect (19% vs 14% placebo). 3
Bisacodyl 10-15 mg once daily can be added before prescription secretagogues, titrating to achieve one non-forced bowel movement every 1-2 days. 3
Additional Medication Options
Probiotics
- Probiotics as a group may improve global symptoms and abdominal pain, but no specific species or strain can be recommended. 1, 2 Advise a 12-week trial and discontinue if no improvement. 1, 5
Bile Acid Sequestrants
- Cholestyramine may benefit approximately 10% of IBS-D patients with bile salt malabsorption, particularly those with <5% retention on SeHCAT testing. 2 Often less well tolerated than loperamide. 5
Critical Implementation Details
Dosing Specifics
TCAs for IBS require lower doses (10-50 mg) than for depression (75-150 mg) and should be taken at bedtime to minimize side effects. 1, 3 Careful explanation of rationale is required as patients may resist "antidepressants." 1
Linaclotide must be taken on an empty stomach at least 30 minutes before the first meal to maximize efficacy. 3
Loperamide can be used prophylactically before situations where diarrhea would be problematic, not just as needed. 2, 5
Monitoring and Duration
Review treatment efficacy after 3 months and discontinue ineffective medications. 1, 2, 5 Do not continue ineffective therapies indefinitely. 3
TCAs should be continued for at least 6 months if symptomatic response occurs. 1, 3
Common Pitfalls to Avoid
Do not prescribe anticholinergic antispasmodics (dicyclomine, hyoscyamine) for IBS-C as they worsen constipation through reduced motility and enhanced water reabsorption. 3
Do not use docusate (stool softener) as it lacks efficacy for constipation and should be stopped immediately. 3
TCAs may worsen constipation in IBS-C patients through anticholinergic effects; ensure adequate laxative therapy is in place before starting. 3
Rifaximin is not effective for methadone-induced constipation or other diphenylheptane opioids. 7
Lubiprostone is contraindicated in mechanical gastrointestinal obstruction and may cause syncope/hypotension, particularly within an hour of the first dose. 7