What is the best medication for a patient with Irritable Bowel Syndrome (IBS)?

Best Medicine for Irritable Bowel Syndrome

The best medication for IBS depends critically on the predominant symptom subtype: for IBS with diarrhea (IBS-D), tricyclic antidepressants (TCAs) are the most effective treatment for global symptoms and abdominal pain; for IBS with constipation (IBS-C), linaclotide is the most effective second-line agent after fiber fails; and for mixed IBS, TCAs remain the most effective first-line pharmacological option. 1, 2, 3

Treatment Algorithm by IBS Subtype

IBS with Diarrhea (IBS-D)

First-line pharmacological treatment:

• Loperamide 4-12 mg daily is the initial medication for controlling stool frequency, urgency, and fecal soiling, though it has limited effect on abdominal pain 1, 2
• For meal-related abdominal pain, antispasmodics with anticholinergic properties (dicyclomine 40 mg four times daily) can be added, though dry mouth, visual disturbance, and dizziness limit tolerability 1, 2, 4

Second-line treatment (most effective):

• Tricyclic antidepressants are the most effective pharmacological treatment for IBS-D, addressing both global symptoms and abdominal pain 5, 1, 2
• Start amitriptyline 10 mg once nightly and titrate slowly (by 10 mg/week) to 30-50 mg daily 1, 2
• Continue for at least 6 months if symptomatic response occurs 1, 2
• TCAs work through neuromodulatory and analgesic properties independent of their psychotropic effect, normalizing rapid small bowel transit in IBS-D 5, 2

Third-line options:

• 5-HT3 receptor antagonists (ondansetron 4 mg once daily, titrating to maximum 8 mg three times daily) are highly efficacious for IBS-D 1, 3
• Rifaximin (non-absorbable antibiotic) is effective for global symptoms, though its effect on abdominal pain is limited 1, 3

IBS with Constipation (IBS-C)

First-line treatment:

• Soluble fiber (ispaghula/psyllium) 3-4 g/day, gradually increased to avoid bloating, is effective for global symptoms and abdominal pain 1, 6
• Avoid insoluble fiber (wheat bran) as it consistently worsens IBS-C symptoms 1, 6
• Polyethylene glycol (osmotic laxative) for constipation, titrated according to symptoms 1

Second-line treatment (most effective):

• Linaclotide 290 mcg once daily on an empty stomach is the most effective second-line agent for IBS-C, addressing both abdominal pain and constipation with high-quality evidence 1, 3
• Lubiprostone 8 mcg twice daily is an alternative if linaclotide is not tolerated, though nausea is a frequent side effect 1, 3

Third-line for refractory pain:

• TCAs (amitriptyline 10-50 mg nightly) are effective for abdominal pain but must be used cautiously with adequate laxative therapy in place, as they can worsen constipation through anticholinergic effects 1, 3

IBS with Mixed Symptoms (IBS-M)

First-line pharmacological treatment:

• TCAs (amitriptyline 10 mg once daily, titrating to 30-50 mg) are the most effective first-line pharmacological treatment for IBS-M, with high-quality evidence 1, 3
• Antispasmodics can be added for abdominal pain, particularly when symptoms are meal-related 1

Symptom-specific management:

• Loperamide 2-4 mg up to four times daily for diarrhea episodes 1
• Polyethylene glycol or bisacodyl 10-15 mg daily for constipation episodes 1

Universal First-Line Non-Pharmacological Approaches

Before or alongside medication:

• Regular physical exercise should be recommended to all IBS patients 1, 2
• Soluble fiber (ispaghula) starting at 3-4 g/day, gradually increased 1, 6
• A 12-week trial of probiotics for global symptoms and bloating; discontinue if no improvement 1, 2
• Symptom diary for 2 weeks to identify dietary triggers 2, 7

Psychological Therapies for Refractory Cases

When symptoms persist despite 12 months of pharmacological treatment:

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

Critical Pitfalls to Avoid

Subtype-specific errors:

• Never prescribe anticholinergic antispasmodics (dicyclomine) for IBS-C, as they reduce intestinal motility and worsen constipation 1, 3
• Do not use TCAs as first-line in IBS-C without adequate laxative therapy in place 1, 3

General errors:

• Do not recommend IgG antibody-based food elimination diets—they lack evidence 1, 2
• Do not recommend gluten-free diet unless celiac disease is confirmed 1, 2
• Avoid insoluble fiber (wheat bran) in all IBS subtypes as it worsens symptoms 1, 6
• Review efficacy after 3 months and discontinue if no response 1

Strength of Evidence Hierarchy

The 2025 guidelines from the American College of Gastroenterology and British Society of Gastroenterology 1 represent the most recent and highest quality evidence, superseding the 2000 British guidelines 5. TCAs have the strongest evidence base across all IBS subtypes for global symptoms and abdominal pain, with multiple large randomized controlled trials demonstrating superiority over placebo 5, 1. Linaclotide has strong evidence specifically for IBS-C with FDA approval 1, 3. The evidence for antispasmodics is weaker and more heterogeneous, with dicyclomine showing 82% response vs 55% placebo in FDA trials 4, but guidelines rate this as low-quality evidence due to study limitations 1, 3.