Tricyclic Antidepressants Most Effective Among Gut–Brain Neuromodulators for IBS
Gut–brain neuromodulators, particularly tricyclic antidepressants (TCAs), show moderate evidence of effectiveness in alleviating irritable bowel syndrome (IBS) symptoms, according to a newly updated systematic review and meta-analysis of randomized controlled trials (RCTs) published in The Lancet Gastroenterology & Hepatology.
Researchers analyzed data from 28 RCTs involving 2,475 adults with IBS to assess whether these pharmacologic agents, which target the gut–brain axis, offer meaningful symptom relief. Compared with placebo, gut–brain neuromodulators were associated with a significant reduction in both global IBS symptoms and abdominal pain.
TCAs demonstrated the strongest and most consistent benefits across 11 trials (1,144 patients), reducing the risk of persistent IBS symptoms by 30% (RR 0.70, 95% CI 0.62–0.80). They also led to a similar reduction in abdominal pain (RR 0.69, 95% CI 0.54–0.87). Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) showed modest benefits in smaller studies, but the evidence was of lower certainty.
Importantly, while adverse events were not significantly more common overall, patients receiving gut–brain neuromodulators were more likely to withdraw from treatment due to side effects. The strength of evidence was rated moderate for TCAs in managing global IBS symptoms, but low to very low for all other drug classes and endpoints.
These findings bolster existing clinical guidelines recommending TCAs as a frontline pharmacologic option for patients with persistent global symptoms or abdominal pain due to IBS. The study also underscores the need for further research into the role of SSRIs, SNRIs, and other neuromodulator classes in this population.
Reference
Khasawneh M, Mokhtare M, Moayyedi P, Black CJ, Ford AC. Efficacy of gut-brain neuromodulators in irritable bowel syndrome: an updated systematic review and meta-analysis. Lancet Gastroenterol Hepatol. Published online: April 18, 2025. doi:10.1016/S2468-1253(25)00051-2
