What medications are used to treat irritable bowel syndrome (IBS)?

Medications for Irritable Bowel Syndrome

Start with lifestyle modifications and soluble fiber (ispaghula 3-4 g/day), then escalate to symptom-specific pharmacological therapy based on the predominant bowel pattern, with tricyclic antidepressants (amitriptyline 10 mg nightly) as the most effective second-line treatment for refractory symptoms. 1, 2

First-Line Treatment Approach

Universal Recommendations for All IBS Patients

• Prescribe regular physical exercise to every patient as the foundation of treatment, as this improves global symptoms and constipation with benefits persisting up to 5 years. 1, 2

• Begin soluble fiber supplementation (ispaghula/psyllium) at 3-4 g/day and titrate gradually to avoid bloating and gas, which is effective for both global symptoms and abdominal pain. 1, 2

• Avoid insoluble fiber (wheat bran) entirely, as it consistently worsens symptoms, particularly bloating. 1, 2

• Trial probiotics for 12 weeks for global symptoms and abdominal pain, though no specific strain can be recommended; discontinue if no improvement occurs. 1, 2

Patient Education

• Explain IBS as a disorder of gut-brain interaction with a benign but relapsing/remitting course to establish realistic expectations and reduce anxiety. 1, 2

• Introduce the concept of the gut-brain axis and how it is impacted by diet, stress, and emotional responses to symptoms. 1

Symptom-Specific Pharmacological Treatment (After 3 Months if First-Line Fails)

For Abdominal Pain and Cramping

• Use antispasmodics (dicyclomine or mebeverine) as first-line pharmacological therapy, particularly when symptoms are meal-related. 1, 2

• Common side effects include dry mouth, visual disturbance, and dizziness. 1, 2

• Peppermint oil can be used as an alternative antispasmodic for abdominal pain. 3, 4

For Diarrhea-Predominant IBS (IBS-D)

First-line:

• Prescribe loperamide 2-4 mg up to four times daily (either regularly or prophylactically before going out) to reduce stool frequency, urgency, and fecal soiling. 1, 2

• Titrate the dose carefully as abdominal pain, bloating, nausea, and constipation may limit tolerability. 1, 2

Second-line (for refractory IBS-D):

• Consider 5-HT3 receptor antagonists (ondansetron titrated from 4 mg once daily to maximum 8 mg three times daily) in secondary care, with constipation being the most common side effect. 2, 3

• Eluxadoline is FDA-approved for IBS-D in adults 5, but is contraindicated in patients without a gallbladder due to risk of pancreatitis and sphincter of Oddi spasm. 5

• Rifaximin (non-absorbable antibiotic) is effective as second-line therapy for IBS-D, with the most favorable safety profile among approved agents. 6

• Avoid alosetron except in women with severe IBS-D refractory to other treatments due to risk of ischemic colitis. 6, 4

For Constipation-Predominant IBS (IBS-C)

First-line:

• Increase dietary fiber to 25 g/day or use ispaghula/psyllium as described above. 2, 3

• Consider polyethylene glycol (osmotic laxative) if fiber supplementation is insufficient, titrating the dose according to symptoms. 1, 3

Second-line (for refractory IBS-C):

• Linaclotide is the most effective secretagogue available for IBS-C and should be the preferred second-line agent when first-line therapies fail; warn patients that diarrhea is a common side effect. 2, 3

• Lubiprostone is FDA-approved for IBS-C in women at least 18 years old at 8 mcg twice daily with food, with nausea being the most common side effect. 7

• Lubiprostone is also approved for chronic idiopathic constipation in adults at 24 mcg twice daily. 7

For Mixed IBS (IBS-M) or Unclassified IBS

• Tricyclic antidepressants (TCAs) are the most effective first-line pharmacological treatment for mixed IBS, as they address both pain and bowel symptoms. 3

• Antispasmodics can be effective for reducing abdominal pain and global symptoms in mixed presentations. 3

Second-Line Treatment for Refractory Symptoms (After 3 Months of Symptom-Specific Therapy)

Gut-Brain Neuromodulators

Tricyclic Antidepressants (First Choice):

• Start amitriptyline 10 mg once daily at bedtime and titrate slowly (by 10 mg/week) according to response and tolerability to a maximum of 30-50 mg once daily. 1, 2, 3

• Provide careful explanation that these are used as gut-brain neuromodulators, not for depression. 1, 2

• Continue for at least 6 months if the patient reports symptomatic response. 1, 3

• TCAs may worsen constipation, so use cautiously in IBS-C and ensure adequate laxative therapy is in place. 3

Selective Serotonin Reuptake Inhibitors (SSRIs):

• Consider SSRIs as an alternative when TCAs are not tolerated or worsen constipation, with a lower side effect profile compared to TCAs. 1, 3

• SSRIs may be effective for global symptoms when TCAs fail. 3

Psychological Therapies (For Symptoms Persisting After 12 Months of Pharmacological Treatment)

• Refer for IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy when symptoms persist despite 12 months of pharmacological treatment. 1, 2, 3

• Consider earlier referral for patients who relate symptom exacerbations to stressors or have associated anxiety/depression. 2, 3

• These therapies are effective for reducing abdominal pain, diarrhea, and global symptoms. 3, 8

Critical Pitfalls to Avoid

• Review treatment efficacy after 3 months and discontinue if no response, as prolonged ineffective therapy wastes time and resources. 1, 2, 3

• 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

• Avoid opioids for chronic abdominal pain management due to risks of dependence and complications. 2, 3

• Do not recommend IgG antibody-based food elimination diets, as they lack evidence and may lead to unnecessary dietary restrictions. 3

• Do not recommend gluten-free diets unless celiac disease has been confirmed, as evidence does not support their use in IBS. 2, 3

• Avoid chronic use of loperamide with eluxadoline due to potential for severe constipation; loperamide may only be used occasionally for acute severe diarrhea and must be discontinued if constipation develops. 5

• Never prescribe eluxadoline to patients without a gallbladder due to high risk of pancreatitis and sphincter of Oddi spasm, which can be fatal. 5

Treatment Algorithm Summary

1. All patients: Exercise + soluble fiber (ispaghula 3-4 g/day) + probiotics trial (12 weeks) 1, 2

2. If inadequate response after 3 months, add symptom-specific therapy:

   • IBS-D: Loperamide 2-4 mg up to 4x daily 1, 2
   • IBS-C: Polyethylene glycol (titrate to response) 1, 3
   • Pain: Antispasmodics (dicyclomine) or peppermint oil 1, 2, 3

3. If still inadequate after 3 months, escalate to:

   • All subtypes: Amitriptyline 10 mg nightly, titrate to 30-50 mg 1, 2, 3
   • Refractory IBS-D: Ondansetron 4-8 mg, rifaximin, or eluxadoline (if has gallbladder) 2, 5, 6
   • Refractory IBS-C: Linaclotide or lubiprostone 2, 3, 7

4. If symptoms persist after 12 months of pharmacological treatment: Refer for IBS-specific CBT or gut-directed hypnotherapy 1, 2, 3