Predictors of response to low-dose amitriptyline for irritable bowel syndrome and efficacy and tolerability according to subtype: post hoc analyses from the ATLANTIS trial

Alexandra Wright-Hughes, Pei-Loo Ow, Sarah L Alderson, Matthew J Ridd, Robbie Foy, Felicity L Bishop, Matthew Chaddock, Catherine Fernandez, Elspeth A Guthrie, Delia P Muir, Christopher A Taylor, Amanda J Farrin, Hazel A Everitt, Alexander C Ford*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.
Original languageEnglish
Article numbergutjnl-2024-334490
Pages (from-to)728-739
Number of pages12
JournalGut
Volume74
Issue number5
Early online date25 Jan 2025
DOIs
Publication statusE-pub ahead of print - 25 Jan 2025

Bibliographical note

Publisher Copyright:
© Author(s) (or their employer(s)) 2025.

Keywords

  • IRRITABLE BOWEL SYNDROME
  • ABDOMINAL PAIN

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