What are the treatment options for functional gastrointestinal (GI) disease, such as irritable bowel syndrome (IBS)?

Treatment of Functional Gastrointestinal Disease

For functional GI disease, particularly IBS, initiate treatment with a low FODMAP diet under dietitian supervision combined with regular exercise, followed by tricyclic antidepressants (starting at 10 mg amitriptyline daily, titrating to 30-50 mg) for persistent symptoms, while avoiding opiates entirely for chronic pain management. 1, 2

Initial Diagnostic Approach

Before treating functional GI symptoms, exclude organic disease through targeted testing rather than extensive workup:

• Measure fecal calprotectin to distinguish inflammatory from functional symptoms, particularly in patients with suspected IBD overlap 3
• Perform serological testing for celiac disease in appropriate patients 4
• Evaluate for anatomic abnormalities in patients with obstructive symptoms including distention, nausea, vomiting, or constipation 3
• Consider alternative mechanisms based on symptom patterns: small intestinal bacterial overgrowth (SIBO), bile acid diarrhea, carbohydrate intolerance, or pancreatic insufficiency 3

First-Line Treatment: Lifestyle and Dietary Modifications

Exercise

• Recommend regular physical exercise to all patients as it provides significant symptom improvement with minimal risk 1, 2, 5

Dietary Interventions

• Initiate a supervised low FODMAP diet delivered in three phases (restriction, reintroduction, personalization) for patients with moderate to severe symptoms, as this has the most robust evidence for reducing overall symptom burden 1, 2, 6
• Ensure dietary instruction is delivered by a trained dietitian to prevent nutritional deficiencies, particularly important in conditions where undernutrition is common 3
• Identify and reduce excessive intake of lactose, fructose, sorbitol, caffeine, or alcohol in diarrhea-predominant patients 1, 2
• Increase soluble fiber (ispaghula/psyllium) starting at 3-4 g/day and gradually increase for constipation-predominant IBS, though avoid in those with bloating 1, 2, 4
• Do not recommend gluten-free diets unless celiac disease is confirmed, as fructans (not gluten) are the likely culprit in symptom improvement 3, 4

Second-Line Treatment: Pharmacological Therapy

For Diarrhea-Predominant IBS

• Prescribe loperamide 4-12 mg daily (either regularly or prophylactically) as the most effective first-line pharmacological treatment for reducing stool frequency and urgency 1, 2, 5
• Consider bile acid sequestrants (cholestyramine) for the approximately 10% of IBS-D patients with bile salt malabsorption, particularly those with <5% retention on SeHCAT testing 1
• Rifaximin may be used for IBS-D, though its effect on abdominal pain is limited 5, 4
• Alosetron (5-HT3 antagonist) is highly efficacious for severe diarrhea-predominant IBS in women, though carries risk of ischemic colitis (0.2% through 3 months) and constipation (29% at 1 mg twice daily) 5, 7

For Constipation-Predominant IBS

• Use osmotic and stimulant laxatives as first-line therapy 3
• Consider secretagogues (lubiprostone, linaclotide) for refractory constipation 3, 4

For Abdominal Pain

• Prescribe antispasmodics with anticholinergic properties (dicyclomine) for pain relief, as they show greater efficacy than direct smooth muscle relaxants 1, 2
• Initiate tricyclic antidepressants (TCAs) at 10 mg amitriptyline once daily, titrating slowly to 30-50 mg daily for global symptoms and pain, as TCAs have high-strength evidence for efficacy 1, 2, 5
• Continue TCAs for at least 6 months if the patient reports symptomatic improvement 2
• Use SSRIs only if TCAs are not tolerated or if concurrent mood disorder requires treatment, as SSRIs have lower strength of evidence for IBS symptoms 1, 2
• Never prescribe opiates for chronic abdominal pain in functional GI disease, as they increase risk of overdose and cause opioid-induced GI side effects 3, 5

Adjunctive Therapies

• Recommend a 12-week trial of probiotics for global symptoms and abdominal pain, discontinuing if no improvement 1, 2, 5
• Consider peppermint oil as an antispasmodic with sufficient safety data 6, 4

Third-Line Treatment: Psychological Therapies

• Refer for IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy when symptoms persist despite pharmacological treatment for 12 months 1, 2, 5
• These brain-gut behavior therapies differ from standard psychological therapies targeting depression and anxiety alone, and have strong evidence for abdominal symptoms in IBS 3, 2
• Consider simple relaxation therapy as an initial approach before formal psychological intervention 1, 2

Special Considerations for IBD Patients with Functional Symptoms

When functional GI symptoms overlap with IBD:

• Use fecal calprotectin and endoscopy with biopsy to distinguish active inflammation from functional symptoms 3
• Apply the same dietary and psychological interventions as for primary IBS, though evidence is less robust in IBD populations 3
• TCAs have demonstrated clinically relevant benefit in retrospective cohort studies of IBD patients with functional symptoms 3, 5
• Rifaximin may benefit the subset with breath-test diagnosed SIBO, though formal evaluation in IBD is limited 3
• Avoid opiates particularly in IBD patients with IBS symptoms after remission of acute inflammation 3

Treatment Monitoring and Adjustment

• Review treatment efficacy after 3 months and discontinue ineffective medications 1, 2, 5
• Recognize that symptoms relapse and remit over time, requiring periodic adjustment of treatment strategy 1, 2, 5
• Avoid extensive testing once IBS diagnosis is established, as this increases healthcare costs without improving outcomes 1, 2

Critical Pitfalls to Avoid

• Never pursue restrictive diets without dietitian supervision, as nutritional deficiencies are a significant risk, particularly in IBD patients 3
• Do not use codeine routinely despite its efficacy for diarrhea, as central nervous system effects and dependency risk often limit use 1, 2
• Avoid prescribing loperamide for "overall IBS symptoms" as it specifically targets diarrhea and urgency, not pain or global symptoms 4
• Do not recommend herbal therapies or acupuncture as routine treatments given insufficient evidence 4
• Never continue ineffective treatments beyond 3 months without reassessment 1, 2