GI Neuromodulator Selection for IBS-C and IBS-M

Primary Recommendation: Tricyclic Antidepressants

The British Society of Gastroenterology recommends tricyclic antidepressants (TCAs) as the first-line neuromodulator for both IBS-C and IBS-M, with a strong recommendation and moderate quality evidence 1, 2
TCAs are effective for abdominal pain reduction (RR 0.53; 95% CI 0.34-0.83) across all IBS subtypes, according to the Clinical Gastroenterology and Hepatology 3, 4
Secondary amine TCAs (nortriptyline, desipramine) are preferred over tertiary amines (amitriptyline, imipramine) in IBS-C to minimize constipation-worsening anticholinergic effects 1, 2

The initial dose of TCAs should be 10 mg at bedtime (amitriptyline or nortriptyline), with titration by 10 mg weekly or every 2 weeks based on response and tolerability 1, 2, 3, 4
The target dose is 30-50 mg once daily at night 1, 2

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are a reasonable second-line alternative when TCAs are not tolerated or contraindicated, particularly for IBS-M, with a starting dose of duloxetine 30 mg once daily 3, 4, 5
SNRIs can be titrated to 60 mg once daily based on response 3, 4

TCA side effects (sedation, dry mouth, dry eyes, constipation) are common and dose-dependent, and can be minimized by starting with a low dose and titrating slowly 1, 2, 3
SNRI side effects include sedation, dry mouth, constipation or diarrhea, anxiety, reduced appetite, nausea, headache, and fatigue 3, 4