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  • 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

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Neurogastroenterology
Original research
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
  1. Alexandra Wright-Hughes1,
  2. Pei-Loo Ow1,
  3. Sarah L Alderson2,
  4. Matthew J Ridd3,
  5. Robbie Foy2,
  6. Felicity L Bishop4,
  7. Matthew Chaddock5,
  8. Catherine Fernandez1,
  9. Elspeth A Guthrie2,
  10. Delia P Muir1,
  11. Christopher A Taylor1,
  12. Amanda J Farrin1,
  13. Hazel A Everitt6,
  14. Alexander C Ford7,8
  1. 1 Clinical Trial Research Unit, Leeds Institute of Clinical Trials Research, School of Medicine, University of Leeds, Leeds, UK
  2. 2 Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK
  3. 3 Population Health Sciences, University of Bristol, Bristol, UK
  4. 4 Centre for Clinical and Community Applications of Health Psychology, School of Psychology, University of Southampton, Southampton, UK
  5. 5 Let's Cure IBS, Leeds, UK
  6. 6 Primary Care and Population Sciences, University of Southampton, Southampton, UK
  7. 7 Leeds Institute of Medical Research at St. James’s, University of Leeds, Leeds, UK
  8. 8 Leeds Gastroenterology Institute, St James's University Hospital, Leeds, UK
  1. Correspondence to Professor Alexander C Ford; alexford{at}nhs.net

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.

  • IRRITABLE BOWEL SYNDROME
  • ABDOMINAL PAIN

Data availability statement

Data are available on reasonable request. All data requests should be submitted to the corresponding author, ACF, for consideration and would be subject to review by a subgroup of the trial team, which will include the data guarantor, AJF. Access to anonymised data may be granted following this review. All data-sharing activities would require a data-sharing agreement.

https://doi.org/10.1136/gutjnl-2024-334490

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    Data availability statement

    Data are available on reasonable request. All data requests should be submitted to the corresponding author, ACF, for consideration and would be subject to review by a subgroup of the trial team, which will include the data guarantor, AJF. Access to anonymised data may be granted following this review. All data-sharing activities would require a data-sharing agreement.

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    Footnotes

    • AW-H and P-LO are joint first authors.

    • Contributors AW-H and ACF are guarantors. They accepted full responsibility for the work and the conduct of the study, had access to the data and controlled the decision to publish. Specific author contributions: AW-H, P-LO, AJF, HAE and ACF conceived this post hoc analysis study. AW-H and P-LO analysed the data and had full access to, and verified, all the data in the study. AW-H, P-LO, AJF, HAE and ACF interpreted the data. ACF, AW-H and P-LO drafted the manuscript. All authors commented on drafts of the paper. All authors have approved the final draft of the manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. AJF, HAE, ACF as co-last authors.

    • Funding The study was funded by the NIHR Health Technology Assessment Programme (grant reference: 16/162/01). The funder had no role in data collection, analysis, interpretation, writing of the manuscript, or the decision to submit for publication. This report is independent research in response to a commissioned call funded by the NIHR. The views expressed in this publication are those of the authors, not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care.

    • Disclaimer The funder had no role in data collection, analysis, interpretation, writing of the manuscript, or the decision to submit for publication. This report is independent research in response to a commissioned call funded by the NIHR. The views expressed in this publication are those of the authors, not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care.

    • 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.

    • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the Methods section for further details.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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