What is the recommended treatment for irritable bowel syndrome, including non‑pharmacologic measures and medication options for IBS‑D, IBS‑C, and IBS‑M?

Treatment of Irritable Bowel Syndrome

All IBS patients should begin with soluble fiber (psyllium/ispaghula) at 3-4 g/day, gradually titrated upward, combined with regular physical exercise, followed by symptom-specific pharmacotherapy based on whether constipation, diarrhea, or pain predominates. 1, 2

Foundational Non-Pharmacologic Management

Patient Education and Therapeutic Alliance

• Explain IBS as a disorder of gut-brain interaction with a benign, relapsing-remitting (not progressive) course to reduce anxiety and set realistic expectations. 2, 1
• Establish that complete symptom resolution is often not achievable; the goal is symptom relief and improved quality of life. 1

Dietary Modifications (First-Line for All Subtypes)

• Start soluble fiber (psyllium/ispaghula) at 3-4 g/day and increase gradually to avoid bloating and gas; this improves global symptoms and abdominal pain across all IBS subtypes. 1, 2, 3
• Avoid insoluble fiber (wheat bran) completely, as it consistently worsens bloating and overall symptom burden in all IBS subtypes. 1, 2
• Reduce excessive intake of lactose, fructose, sorbitol, caffeine, and alcohol, particularly in IBS-D. 2, 1
• Consider a supervised low-FODMAP diet (restriction, reintroduction, personalization phases) for persistent symptoms after first-line measures fail, but only under guidance of a trained dietitian to prevent nutritional deficits. 2, 3, 4
• Do not recommend gluten-free diets unless celiac disease is confirmed, and do not use IgG antibody-based food elimination diets, as evidence does not support these approaches. 1, 2, 3

Lifestyle Interventions

• Recommend regular physical exercise to all IBS patients as foundational therapy; this provides significant benefits for symptom management. 2, 1
• Advise adequate time for regular defecation and good sleep hygiene. 2

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Pharmacologic Treatment by Predominant Subtype

IBS with Diarrhea (IBS-D)

First-Line Pharmacotherapy

• Loperamide 2-4 mg up to four times daily (regular or prophylactic dosing before outings) reduces stool frequency, urgency, and fecal soiling; titrate carefully to avoid constipation, bloating, or abdominal pain. 1, 2, 3
• Loperamide improves stool consistency but does not affect overall symptom burden or abdominal pain. 1

Second-Line Pharmacotherapy

• Rifaximin (non-absorbable antibiotic) is effective for global IBS-D symptoms, though its effect on abdominal pain is limited. 1, 5
• 5-HT3 receptor antagonists (e.g., ondansetron 4 mg once daily, titrated to maximum 8 mg three times daily) are effective second-line options for diarrhea episodes. 1
• Eluxadoline may be considered for patients with significant diarrhea who do not respond to loperamide or low-FODMAP diet. 5, 3
• Avoid alosetron due to safety concerns. 5

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IBS with Constipation (IBS-C)

First-Line Pharmacotherapy

• After soluble fiber failure, initiate polyethylene glycol (PEG) osmotic laxative, titrated to symptom response; abdominal pain is the most common side effect. 1, 2
• Bisacodyl (stimulant laxative) 10-15 mg once daily can be added, with goal of one non-forced bowel movement every 1-2 days; increase to twice or three times daily if constipation persists after 2-4 weeks. 1

Second-Line Pharmacotherapy (Prescription Secretagogues)

• Linaclotide 290 mcg once daily on an empty stomach (at least 30 minutes before first meal) is the preferred second-line agent for IBS-C; it addresses both abdominal pain and constipation with high-quality evidence. 1, 6, 3, 4
• Diarrhea is the most common adverse event with linaclotide, occurring as the mechanism of action. 1
• Plecanatide is an alternative secretagogue with similar efficacy. 1
• Lubiprostone 8 mcg twice daily with food is a third option for women with IBS-C, though it has a conditional recommendation due to moderate certainty evidence and higher rates of nausea (19% vs 14% placebo). 5, 1, 3

Critical Pitfall for IBS-C

• Do not prescribe anticholinergic antispasmodics (dicyclomine, hyoscyamine) in IBS-C, as they reduce intestinal motility and enhance water reabsorption, which will worsen constipation. 1

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IBS with Mixed Symptoms (IBS-M) or Refractory Abdominal Pain

First-Line for Abdominal Pain

• Antispasmodics with anticholinergic properties (dicyclomine) taken before meals are first-line for meal-related abdominal pain; common side effects include dry mouth, visual disturbances, and dizziness. 1, 6, 2
• Peppermint oil provides an alternative antispasmodic effect with a more favorable side-effect profile. 1, 2, 3

Most Effective Neuromodulator (Second-Line)

• Tricyclic antidepressants (TCAs) are the most effective pharmacological treatment for global symptoms, abdominal pain, and mixed IBS symptoms refractory to first-line measures. 1, 6, 2, 4
• Start amitriptyline 10 mg once daily at bedtime, titrate slowly (by 10 mg/week) to 30-50 mg once daily. 1, 6, 2
• Continue TCAs for at least 6 months if the patient reports symptomatic improvement. 1, 6, 2
• Carefully explain the rationale for using an antidepressant for IBS (not for depression) to improve adherence. 6, 2
• Caution in IBS-C: TCAs may worsen constipation through anticholinergic effects; ensure adequate laxative therapy is in place. 1

Alternative Neuromodulator

• Selective serotonin reuptake inhibitors (SSRIs) may be effective for global symptoms when TCAs are not tolerated or for IBS-C, though pooled data show weaker evidence than TCAs. 1, 2
• SSRIs are preferred if there is concurrent mood disorder requiring treatment. 2
• Avoid SSRIs specifically for IBS symptoms per VA/DoD guidelines. 5

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Psychological Therapies (Third-Line for Refractory Cases)

• IBS-specific cognitive-behavioral therapy (CBT) and gut-directed hypnotherapy should be considered when symptoms persist despite 12 months of pharmacological treatment. 5, 1, 6, 2, 4
• Mindfulness-based cognitive therapy improved quality of life by 32% during treatment and 39% at 6-week follow-up compared to waitlist controls. 5
• Psychological interventions do not improve constipation or persistent abdominal pain and should be considered adjuncts rather than replacements for pharmacotherapy. 1
• Refer to a gastropsychologist if IBS symptoms are moderate to severe, the patient accepts that symptoms relate to gut-brain dysregulation, and has time to devote to learning new coping strategies. 2

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Treatment Monitoring and Adjustment

• Review treatment efficacy after 3 months and discontinue ineffective medications rather than continuing to add therapies. 1, 6, 2
• Recognize that symptoms relapse and remit over time, requiring periodic adjustment of treatment strategy rather than indefinite continuation of all therapies. 6, 2
• If TCAs are effective, maintain for a minimum of 6 months before contemplating discontinuation. 1, 6

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Critical Pitfalls to Avoid

• Do not perform extensive investigations once IBS is diagnosed based on symptom criteria in patients under 45 without alarm features (weight loss, rectal bleeding, family history of IBD/celiac disease, nocturnal diarrhea). 1, 2
• Do not continue docusate (stool softener), as evidence demonstrates it lacks efficacy for constipation. 1
• Do not prescribe opioid medications for pain related to IBS. 5
• Do not use mifepristone for IBS. 5
• Do not prescribe NSAIDs for chronic pain related to IBS. 5

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When to Refer to Gastroenterology

• Diagnostic uncertainty or presence of alarm features. 1
• Severe or refractory symptoms after 12 weeks of appropriate treatment. 1
• Need for supervised low-FODMAP diet requiring trained dietitian. 1, 2
• Consideration of advanced therapies (5-HT3 antagonists, secretagogues) that may require specialist oversight. 6