Efficacy of gut-brain neuromodulators and brain-gut behaviour therapies for irritable bowel syndrome: systematic review and network meta-analysis

Background Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction, with some recommended treatments targeting brain-gut axis dysfunction. Objective To compare relative efficacy of gut-brain neuromodulators and brain-gut behaviour therapies in IBS. Design Network meta-analysis searching the medical literature to 8 February 2026 for randomised controlled trials (RCTs) of gut-brain neuromodulators or brain-gut behaviour therapies in adults with IBS. In our main analysis, we judged efficacy using dichotomous endpoints of improvement in either global IBS symptoms or abdominal pain. We pooled data with a random effects model, with efficacy reported as a pooled relative risk (RR) with 95% CIs. We ranked treatments according to P-score; the mean extent of certainty that one treatment is better than another averaged over all competing treatments. Results We identified 68 eligible RCTs (6694 participants). Compared with waiting list control, in 66 trials (6542 patients), serotonin and norepinephrine reuptake inhibitors (SNRIs) ranked first in six trials (387 patients) (RR of global IBS symptoms or abdominal pain not improving=0.49; 95% CI 0.32 to 0.75, P-score 0.95), meaning the probability that this was the most efficacious treatment was 95%. However, no trials were at low risk of bias. Tricyclic antidepressants (TCAs) ranked second in 15 trials (1519 patients) (RR=0.60; 95% CI 0.43 to 0.85, P-score 0.79) and forms of dynamic psychotherapy/emotional processing third (RR=0.62; 95% CI 0.44 to 0.87, P-score 0.75). Forms of cognitive behavioural therapy (CBT), forms of disease self-management, selective serotonin reuptake inhibitors and forms of gut-directed hypnotherapy (GDH) were also superior to waiting list control. Conclusion Several gut-brain neuromodulators, especially TCAs, and brain-gut behaviour therapies, particularly forms of dynamic psychotherapy/emotional processing, CBT, disease self-management and GDH, are efficacious for IBS. However, there was possible publication bias in some analyses, and overall certainty in the evidence was low or very low for most comparisons.