Gut. 2025 Jan 25:gutjnl-2024-334490. doi: 10.1136/gutjnl-2024-334490. Online ahead of print.

Alexandra Wright-Hughes ¹, Pei-Loo Ow ¹, Sarah L Alderson ², Matthew J Ridd ³, Robbie Foy ², Felicity L Bishop ⁴, Matthew Chaddock ⁵, Catherine Fernandez ¹, Elspeth A Guthrie ², Delia P Muir ¹, Christopher A Taylor ¹, Amanda J Farrin ¹, Hazel A Everitt ⁶, Alexander C Ford ^7 8

Author information

¹Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds, Leeds, UK.

²Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK.

³Population Health Sciences, University of Bristol, Bristol, UK.

⁴Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton, Southampton, UK.

⁵Let's Cure IBS, Leeds, UK.

⁶Primary Care and Population Sciences, University of Southampton, Southampton, UK.

⁷Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK alexford@nhs.net.

⁸Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK.

Abstract

Background: Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.

Objective: To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.

Design: ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype.

Results: There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs <50 on the IBS severity scoring system (IBS-SSS) (interaction p=0.048, mean difference in ≥50 years subgroup -46.5; 95% CI -74.2 to -18.8, p=0.0010), and subjective global assessment of relief (interaction p=0.068, OR in ≥50 years subgroup 2.59; 95% CI 1.47 to 4.55, p=0.0010), and those in the 70% most deprived areas of England compared with the 30% least deprived for a ≥30% improvement in abdominal pain (interaction p=0.021, OR in 70% most deprived subgroup 2.70; 95% CI 1.52 to 4.77, p=0.0007). Stronger treatment effects were seen in men, with higher Patient Health Questionnaire-12 scores, and with IBS with diarrhoea. Mean differences in individual IBS-SSS components favoured amitriptyline, and side effects were similar, across almost all IBS subtypes.

Conclusion: These exploratory analyses demonstrate there are unlikely to be deleterious effects of amitriptyline in any particular IBS subtype and could help identify patients in whom amitriptyline may be more effective.

Trial registration number: ISRCTN48075063.