Cost-effectiveness of low-dose amitriptyline for irritable bowel syndrome in primary care
Cost-effectiveness of low-dose amitriptyline for irritable bowel syndrome in primary care
Objective: general practitioners may not prescribe amitriptyline for irritable bowel syndrome (IBS) despite using it for other chronic conditions. The Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS) trial found low-dose titrated amitriptyline was a safe and clinically effective second-line treatment for IBS in primary care. We undertook a prespecified cost-effectiveness analysis of ATLANTIS trial data.
Design/method: complete case (CC) and a full population (FP) analysis using multiply imputed data with analyses at 6 (365 participants CC, 463 participants FP) and 12 (224 participants CC, 291 participants FP) months. As the trial was not fully randomised between 6 and 12 months, we adopted inverse probability weighting to mitigate potential impact of participants choosing to continue trial medication.
Results: at a 6-month time horizon, CC analysis demonstrated low-dose amitriptyline was more likely to be cost-effective than not (incremental net health benefit (NHB) 0.0029 quality-adjusted life years (QALYs)/person, low-dose amitriptyline dominant, 67.3% probability cost-effective), but not FP analysis. At 12 months, all analyses demonstrated low-dose amitriptyline was more likely to be cost-effective than not (CC: incremental NHB 0.00757 QALYs/person, low-dose amitriptyline dominant, 81.7% probability cost-effective; FP: incremental NHB 0.00388 QALYs/person, low-dose amitriptyline dominant, 68.7% probability cost-effective).
Conclusion: in addition to the clinical benefit, safety and acceptability of low-dose amitriptyline in patients with IBS found in the ATLANTIS trial, these results indicate this inexpensive medication is likely to be cost-effective as a second-line treatment for IBS in primary care over 12 months. This strengthens amitriptyline as a treatment option for people with ongoing IBS symptoms.
Gkountouras, Georgios
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Ford, Alexander Charles
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Wright-Hughes, Alexandra
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Alderson, Sarah
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Ow, Pei-Loo
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Ridd, Matthew
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Foy, Robbie
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Bishop, Felicity
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Chaddock, Matthew
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Fernandez, Catherine
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Guthrie, Elspeth
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Muir, Delia P.
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Farrin, Amanda
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Everitt, Hazel
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Howdon, Daniel
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Gkountouras, Georgios
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Ford, Alexander Charles
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Wright-Hughes, Alexandra
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Alderson, Sarah
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Ow, Pei-Loo
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Ridd, Matthew
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Foy, Robbie
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Bishop, Felicity
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Chaddock, Matthew
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Fernandez, Catherine
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Guthrie, Elspeth
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Muir, Delia P.
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Farrin, Amanda
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Everitt, Hazel
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Howdon, Daniel
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Gkountouras, Georgios, Ford, Alexander Charles, Wright-Hughes, Alexandra, Alderson, Sarah, Ow, Pei-Loo, Ridd, Matthew, Foy, Robbie, Bishop, Felicity, Chaddock, Matthew, Fernandez, Catherine, Guthrie, Elspeth, Muir, Delia P., Farrin, Amanda, Everitt, Hazel and Howdon, Daniel
,
ATLANTIS trialists
(2025)
Cost-effectiveness of low-dose amitriptyline for irritable bowel syndrome in primary care.
Frontline Gastroenterology.
(doi:10.1136/flgastro-2025- 103447).
Abstract
Objective: general practitioners may not prescribe amitriptyline for irritable bowel syndrome (IBS) despite using it for other chronic conditions. The Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS) trial found low-dose titrated amitriptyline was a safe and clinically effective second-line treatment for IBS in primary care. We undertook a prespecified cost-effectiveness analysis of ATLANTIS trial data.
Design/method: complete case (CC) and a full population (FP) analysis using multiply imputed data with analyses at 6 (365 participants CC, 463 participants FP) and 12 (224 participants CC, 291 participants FP) months. As the trial was not fully randomised between 6 and 12 months, we adopted inverse probability weighting to mitigate potential impact of participants choosing to continue trial medication.
Results: at a 6-month time horizon, CC analysis demonstrated low-dose amitriptyline was more likely to be cost-effective than not (incremental net health benefit (NHB) 0.0029 quality-adjusted life years (QALYs)/person, low-dose amitriptyline dominant, 67.3% probability cost-effective), but not FP analysis. At 12 months, all analyses demonstrated low-dose amitriptyline was more likely to be cost-effective than not (CC: incremental NHB 0.00757 QALYs/person, low-dose amitriptyline dominant, 81.7% probability cost-effective; FP: incremental NHB 0.00388 QALYs/person, low-dose amitriptyline dominant, 68.7% probability cost-effective).
Conclusion: in addition to the clinical benefit, safety and acceptability of low-dose amitriptyline in patients with IBS found in the ATLANTIS trial, these results indicate this inexpensive medication is likely to be cost-effective as a second-line treatment for IBS in primary care over 12 months. This strengthens amitriptyline as a treatment option for people with ongoing IBS symptoms.
Text
CLEAN ATLANTIS accepted Health Ec manuscriot
- Accepted Manuscript
More information
Accepted/In Press date: 21 November 2025
e-pub ahead of print date: 21 November 2025
Identifiers
Local EPrints ID: 508816
URI: http://eprints.soton.ac.uk/id/eprint/508816
ISSN: 2041-4137
PURE UUID: 74b5091f-43aa-4b50-b3f5-c00f07058282
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Date deposited: 04 Feb 2026 17:37
Last modified: 19 Feb 2026 02:38
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Contributors
Author:
Georgios Gkountouras
Author:
Alexander Charles Ford
Author:
Alexandra Wright-Hughes
Author:
Sarah Alderson
Author:
Pei-Loo Ow
Author:
Matthew Ridd
Author:
Robbie Foy
Author:
Matthew Chaddock
Author:
Catherine Fernandez
Author:
Elspeth Guthrie
Author:
Delia P. Muir
Author:
Amanda Farrin
Author:
Daniel Howdon
Corporate Author: ATLANTIS trialists
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