What are the prescription management options for a patient with Irritable Bowel Syndrome (IBS)?

Prescription Management of Irritable Bowel Syndrome

Tricyclic antidepressants (TCAs) starting at amitriptyline 10 mg once daily and titrating to 30-50 mg once daily are the most effective first-line prescription therapy for IBS, particularly for abdominal pain and global symptoms, and should be preferred over other pharmacological options. 1, 2, 3

Symptom-Targeted First-Line Pharmacotherapy

For Abdominal Pain

• Antispasmodics with anticholinergic properties (dicyclomine) should be prescribed first for abdominal pain, particularly when symptoms are meal-related, though anticholinergic side effects (dry mouth, visual disturbance, dizziness) commonly limit tolerability 1, 2
• Peppermint oil can be used as an alternative antispasmodic with fewer side effects, though evidence is more limited 2
• If pain persists despite antispasmodics, advance directly to TCAs rather than continuing to trial additional antispasmodics 1, 2, 3

For Diarrhea-Predominant IBS (IBS-D)

• Loperamide 4-12 mg daily is the first-line prescription for diarrhea, either taken regularly or prophylactically before situations where diarrhea would be problematic 1, 2
• Titrate loperamide dose carefully to avoid abdominal pain, bloating, nausea, and paradoxical constipation 1, 2
• Codeine 30-60 mg, 1-3 times daily is a reasonable alternative but central nervous system effects (sedation) often limit use 1, 2
• For patients with nocturnal diarrhea, prior cholecystectomy, or age ≥50 years with severe watery diarrhea, consider bile salt malabsorption and trial cholestyramine, though it is often less well tolerated than loperamide 1, 2

For Constipation-Predominant IBS (IBS-C)

• Soluble fiber supplementation (ispaghula/psyllium) starting at 3-4 g/day and gradually increasing is first-line for constipation 1, 2, 4
• Avoid insoluble fiber (wheat bran) as it exacerbates bloating 1, 2

Second-Line Neuromodulators (When First-Line Therapies Fail)

Tricyclic Antidepressants (Preferred)

• Start amitriptyline or trimipramine at 10 mg once daily at bedtime, titrating slowly to 30-50 mg once daily 1, 2, 3
• TCAs have moderate-quality evidence for efficacy in global symptoms and abdominal pain, making them the strongest second-line option 1, 3
• Continue for at least 6 months if the patient reports symptomatic improvement 2
• Carefully explain the rationale for using an antidepressant for IBS (gut-brain neuromodulation, not depression treatment) to improve adherence 1, 2
• Avoid TCAs if constipation is a major feature, as they worsen constipation through anticholinergic effects 1, 2
• Common side effects include dry mouth, drowsiness, and constipation 1

Selective Serotonin Reuptake Inhibitors (Alternative)

• SSRIs may be considered if TCAs are not tolerated or if there is concurrent mood disorder requiring treatment 1, 2, 3
• SSRIs have lower-quality evidence (weak recommendation) compared to TCAs for IBS-specific symptoms 1
• Monitor for anxiety and disturbed sleep, which can worsen with SSRIs 2

Advanced Second-Line Therapies for Refractory IBS-D (Specialist Prescribing)

5-HT3 Receptor Antagonists (Most Efficacious for IBS-D)

• 5-HT3 antagonists are likely the most efficacious drug class for IBS-D but should be reserved for secondary care due to safety concerns 1
• Alosetron and ramosetron are unavailable in many countries 1
• Ondansetron titrated from 4 mg once daily to maximum 8 mg three times daily is a reasonable alternative 1
• Constipation is the most common side effect and requires careful monitoring 1, 5
• Alosetron carries boxed warnings for ischemic colitis (0.3% incidence through 6 months) and serious complications of constipation (0.1% incidence), including rare cases of perforation and death 5
• Discontinue immediately if constipation develops or if signs of ischemic colitis appear (rectal bleeding, bloody diarrhea, new or worsening abdominal pain) 5

Other Second-Line Options for IBS-D

• Eluxadoline (mixed opioid receptor drug) is efficacious but contraindicated in patients with prior sphincter of Oddi problems, cholecystectomy, alcohol dependence, pancreatitis, or severe liver impairment 1
• Rifaximin (non-absorbable antibiotic) is efficacious but has limited effect on abdominal pain and is not available for IBS in many countries 1

Advanced Second-Line Therapies for Refractory IBS-C (Specialist Prescribing)

Secretagogues

• Linaclotide (guanylate cyclase-C agonist) is likely the most efficacious secretagogue for IBS-C (strong recommendation, high-quality evidence), though diarrhea is a common side effect 1
• Lubiprostone (chloride channel activator) is less likely to cause diarrhea than linaclotide but nausea is a frequent side effect 1
• Plecanatide (another guanylate cyclase-C agonist) has similar efficacy to linaclotide with comparable diarrhea risk 1

Critical Prescribing Pitfalls to Avoid

• Do not prescribe medications without first establishing a positive diagnosis and providing clear explanation about IBS as a gut-brain interaction disorder 2, 4
• Review treatment efficacy after 3 months and discontinue ineffective medications rather than continuing to add therapies 2, 4
• Avoid prescribing drugs in patients with major psychological problems without addressing underlying psychological issues, as this may reinforce abnormal illness behavior 1
• Do not use food elimination diets based on IgG antibodies or recommend gluten-free diets unless celiac disease is confirmed 1, 2
• Recognize that pharmacological treatments have limited value overall, with specific benefit seen only in a limited proportion of patients 1
• The high immediate placebo response wears off with time, causing repeated consultations if expectations are not managed 1

When to Refer for Psychological Therapy

• Consider IBS-specific cognitive behavioral therapy or gut-directed hypnotherapy when symptoms persist despite pharmacological treatment for 12 months 1, 2, 3, 4
• Refer to a gastropsychologist if symptoms are moderate to severe, the patient accepts gut-brain dysregulation as a mechanism, and has time to devote to learning coping strategies 2, 4
• Psychological therapies are specifically designed for IBS and differ from standard depression/anxiety treatments 2

Treatment Monitoring Strategy

• Symptoms typically relapse and remit over time, requiring periodic adjustment of treatment strategy rather than indefinite continuation of all therapies 2, 4
• If TCAs are effective, continue for at least 6 months before attempting to taper 2
• Avoid extensive testing once IBS diagnosis is established unless alarm features develop 2, 4