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. 2025 Apr 7;74(5):728-739.
doi: 10.1136/gutjnl-2024-334490.

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  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
Affiliations

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 et al. Gut. .

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.

Keywords: ABDOMINAL PAIN; IRRITABLE BOWEL SYNDROME.

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Conflict of interest statement

Competing interests: AW-H: NIHR grant funding paid to her institution, Data Monitoring and Ethics Committee and Trial Steering Committee member of NIHR and MRC funded projects, travel reimbursement for expert Committee membership of the Yorkshire and Northeast Regional Advisory Committee for NIHR Research for Patient Benefit. P-LO: none. SLA: NIHR, YCR and Health Data Research UK grant funding paid to her institution, consulting fees from West Yorkshire Integrated Care Board paid to her institution, speaker’s payments from Xytal, and grant funding panel member for NIHR. MJR: NIHR grant funding paid to his institution. RF: NIHR and YCR grant funding paid to his institution, Chair of NICE Implementation Strategy Group. FLB: none. MC: none. CF: none. EAG: NIHR and Leeds Hospitals Charity grant funding paid to her institution. DPM: none. CAT: none. AJF: NIHR grant funding paid to her institution, Data Monitoring and Ethics Committee and Trial Steering Committee member of NIHR and BHF funded projects, and NIHR senior investigator. HAE: NIHR grant funding paid to her institution. ACF: NIHR grant funding paid to his institution.

Figures

Figure 1
Figure 1. Forest Plot of Treatment Effects on the Total IBS-SSS score at 6 Months According to Participant Baseline Characteristics.
Figure 2
Figure 2. Forest Plot of Treatment Effects on SGA of Relief of IBS Symptoms at 6 Months According to Participant Baseline Characteristics.
Figure 3
Figure 3. Forest Plot of Treatment Effects on a ≥30% Improvement in Abdominal Pain at 6 Months According to Participant Baseline Characteristics.
See this image and copyright information in PMC

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