Journal Article

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

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

2025

Overview

BackgroundLow-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.ObjectiveTo perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.DesignATLANTIS 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.ResultsThere 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.ConclusionThese 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.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group LTD
• Subject: Abdomen / ABDOMINAL PAIN / Adult / Aged / Amitriptyline / Amitriptyline - administration & dosage / Amitriptyline - adverse effects / Antidepressive Agents, Tricyclic - administration & dosage / Antidepressive Agents, Tricyclic - adverse effects / Anxiety / Constipation / Diarrhea / Double-Blind Method / Drug dosages / Female / Humans / Intestine / IRRITABLE BOWEL SYNDROME / Irritable Bowel Syndrome - complications / Irritable Bowel Syndrome - drug therapy / Male / Middle Aged / Motility / Multicenter Studies as Topic / Neurogastroenterology / Pain / Patients / Placebos / Questionnaires / Randomized Controlled Trials as Topic / Secondary Data Analysis / Severity of Illness Index / Side effects / Treatment Outcome