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Efficacy of gut-brain neuromodulators in irritable bowel syndrome: an updated systematic review and meta-analysis

Mais Khasawneh, M. Mokhtare, P. Moayyedi, C. Black, Alexander C. Ford

The Lancet Gastroenterology and Hepatology, 2025

2,475 participants · 25 citations

Abstract

BACKGROUND

Gut-brain neuromodulators might be efficacious for irritable bowel syndrome (IBS), but there has been no synthesis of evidence from randomised controlled trials (RCTs) of some drug classes, and whether they have pain-modifying properties in IBS is unclear. We updated a previous systematic review and meta-analysis of RCTs examining these questions.

METHODS

We searched MEDLINE (from Jan 1, 1946, to Jan 1, 2025), Embase and Embase Classic (from Jan 1, 1947, to Jan 1, 2025), and the Cochrane Central Register of Controlled Trials (from database inception to Jan 1, 2025). Trials recruiting adults with IBS and that compared gut-brain neuromodulators versus placebo over at least 4 weeks of treatment were eligible. Dichotomous symptom data were pooled using a random effects model to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% CI.

FINDINGS

The search strategy identified 3625 citations. 28 RCTs were eligible containing 2475 patients. Ten RCTs were identified since our previous meta-analysis, containing 1348 patients. The RR of global IBS symptoms not improving with gut-brain neuromodulators versus placebo in 22 RCTs (2222 patients) was 0·77 (95% CI 0·69-0·87). The best evidence in terms of persistence of global IBS symptoms was for tricyclic antidepressants (TCAs) in 11 trials (1144 patients; RR 0·70, 0·62-0·80). The RR of abdominal pain not improving with gut-brain neuromodulators versus placebo in 19 RCTs (1792 patients) was 0·72 (95% CI…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 2,475 participants or records.

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