What is the best treatment for Irritable Bowel Syndrome (IBS) with constipation?

Treatment of IBS with Constipation

Start with osmotic laxatives (polyethylene glycol) as first-line therapy, then escalate to linaclotide as the most effective second-line agent if symptoms persist after 4 weeks. 1

First-Line Approach: Lifestyle and Dietary Modifications

• Begin with regular physical exercise for all IBS-C patients, as this improves global symptoms and should form the foundation of treatment 2

• Initiate soluble fiber supplementation with ispaghula or psyllium starting at 3-4 g/day, gradually increasing the dose to avoid bloating and gas 1, 2, 3

  • Soluble fiber is effective for both global symptoms and abdominal pain with a number needed to treat of 7 3
  • Avoid insoluble fiber (wheat bran, corn fiber) as it consistently worsens symptoms and provides no benefit 2, 3

• Start polyethylene glycol (osmotic laxative) for constipation, titrating the dose according to symptoms 1

  • This is reasonable first-line therapy based on efficacy in chronic constipation generally, despite limited specific evidence in IBS-C 1
  • Abdominal pain is the most common side effect 1
  • Evidence is limited to 4-week trials, so long-term efficacy is unknown 1

• Consider a 12-week trial of probiotics for global symptoms and abdominal pain, discontinuing if no improvement occurs 2

Second-Line Pharmacological Treatment for Persistent Symptoms

For Abdominal Pain

• Use antispasmodics (such as dicyclomine or hyoscyamine) for abdominal pain and global symptoms 1, 2

  • These rank third overall for global symptoms in network meta-analysis 1
  • Common side effects include dry mouth, visual disturbance, and dizziness 1

• Peppermint oil is an alternative antispasmodic that ranks first in network meta-analysis for global symptoms 1

  • Gastroesophageal reflux is a common side effect due to effects on the lower esophageal sphincter 1

For Refractory Constipation: Secretagogues

Linaclotide is the most effective secretagogue available for IBS-C and should be the preferred second-line agent when first-line therapies fail 1, 4

• This is a guanylate cyclase-C agonist that softens stools and accelerates gut transit 1, 4
• Strong recommendation with high-quality evidence 1
• Diarrhea is a common side effect 1
• FDA-approved specifically for IBS-C in adults 4

Lubiprostone is an alternative secretagogue if linaclotide is not tolerated 1, 5

• This chloride channel activator is less likely to cause diarrhea than linaclotide 1
• Nausea is a frequent side effect that can be reduced by taking with food 5
• Strong recommendation with moderate-quality evidence 1
• FDA-approved for IBS-C in women ≥18 years old 5

Other secretagogues with more limited availability:

• Plecanatide (guanylate cyclase-C agonist): weak recommendation, very low evidence quality, diarrhea common 1
• Tenapanor (sodium-hydrogen exchange inhibitor): strong recommendation, high evidence quality, but unavailable in many countries 1
• Tegaserod (5-HT4 agonist): strong recommendation, moderate evidence quality, but unavailable outside USA 1

Third-Line Treatment: Neuromodulators for Refractory Pain

Tricyclic antidepressants (TCAs) are effective for global symptoms and abdominal pain when other treatments fail 1, 2

• Start amitriptyline at 10 mg once daily at bedtime, titrating slowly to 30-50 mg daily 1, 2
• Use cautiously in IBS-C as TCAs may worsen constipation; ensure adequate laxative therapy is in place 2
• Continue for at least 6 months if patient reports symptomatic response 1, 2
• Careful explanation of rationale is required, as patients may be concerned about using an antidepressant 1

SSRIs are an alternative neuromodulator when TCAs are not tolerated or worsen constipation 2

• Weak recommendation with low-quality evidence 1

Psychological Therapies for Persistent Symptoms

Consider psychological interventions early rather than waiting for multiple drug failures, as they have low risk of harm and build lifelong management skills 1

• IBS-specific cognitive behavioral therapy is effective for global symptoms 1, 2

  • Strong recommendation with low-quality evidence 1

• Gut-directed hypnotherapy is effective for global symptoms 1, 2

  • Strong recommendation with low-quality evidence 1

• Guidelines typically recommend these when symptoms have not responded after 12 months of drug treatment, but earlier referral is reasonable if accessible and patient is willing 1, 2

Critical Pitfalls to Avoid

• Do not recommend gluten-free diets unless celiac disease has been confirmed 2
• Avoid IgG antibody-based food elimination diets as they lack evidence and may lead to unnecessary dietary restrictions 2
• Manage patient expectations: complete symptom resolution is often not achievable; the goal is symptom relief and improved quality of life 1
• Review efficacy after 3 months of any treatment and discontinue if no response 2
• Avoid opioids for chronic abdominal pain management due to risks of dependence and complications 2