ATLANTIS

Important Information for Patients and Primary Care Providers

Executive Summary of ATLANTIS results

Background: People with irritable bowel syndrome (IBS) experience tummy (abdominal) pain and changes to their bowel movements. IBS can have a serious impact on people’s lives. Previous small trials suggest that a drug called amitriptyline used at a low dose may help IBS. Amitriptyline is already used to treat other conditions. It’s available for IBS but isn’t used much by general practitioners (GPs).

Methods: We recruited adults aged ≥18 years with ongoing IBS symptoms from UK general practices. Patients received either low-dose amitriptyline or placebo (a dummy tablet) for 6 months. Patients could adjust the dose according to symptoms and side effects. Neither the researchers nor the patients knew which treatment they were getting. Participants recorded symptoms using a questionnaire containing an IBS severity score. We looked at the difference in average IBS severity score between patients receiving amitriptyline and placebo. We also looked at effect of amitriptyline on mood, ability to work, and non-gut symptoms related to IBS, as well as safety and acceptability. Some patients and GPs were interviewed about their experiences.

Results: 463 patients took part from 55 general practices across England. Participants receiving amitriptyline reported a bigger improvement in their IBS severity scores at 6 months, compared with patients on placebo. Amitriptyline was better across a range of IBS symptom measures and safe. Patients found it more acceptable than placebo. It did not impact anxiety, depression, or ability to work. Patients liked being able to adjust their dose and valued contact with the research team.

Conclusion: This study showed that amitriptyline is more effective than a placebo and is safe. GPs should offer low-dose amitriptyline to people with IBS if symptoms don’t improve with other standard treatments. Patients should be supported and helped to adjust their dose as needed. The dose adjustment sheet used in this trial is freely available to download from this website.

ATLANTIS Trial Results

ATLANTIS trial main results: https://authors.elsevier.com/sd/article/S0140-6736(23)01523-4

ATLANTIS protocol paper: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06492-6

ATLANTIS qualitative results: Low-dose amitriptyline for irritable bowel syndrome: a qualitative study of patients’ and GPs’ views and experiences

NIHR Alert May 2024: Irritable bowel syndrome: low dose antidepressant improves symptoms.

BMJ.com: Irritable bowel syndrome: low dose antidepressant improves symptoms

Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT https://www.journalslibrary.nihr.ac.uk/hta/BFCR7986#/abstract

ATLANTIS prizes awarded

British Society of Gastroenterology, 19 – 22 June 2023, Liverpool: Awarded “Best Oral Presentation in the neuro-gastroenterology section”
“Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment (The ATLANTIS study): A Double-blind Placebo-controlled Trial”

Royal College of General Practitioners Conference, 19 – 20 October 2023, Glasgow, UK – Awarded the “winning e-poster in the clinical category”
“Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment (The ATLANTIS study): A Double-blind Placebo-controlled Trial in Primary Care”

North American Primary Care Researcher Group (NPCRG), 30 Oct – 3 Nov 2023, San Francisco, USA – Awarded the “2023 NAPCRG Distinguished Paper Award”
“Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome in Primary Care: ATLANTIS: Randomised Controlled Trial”

Royal College of General Practitioners Conference, 3-4 October 2024, Liverpool –Awarded overall “RCGP Research paper of the year 2023” and winner of the “Clinical Research Award”
“Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial”
https://bjgplife.com/rcgp-research-paper-of-the-year-lessons-for-the-next-generation/

Top study in primary care from 2023 according to Canadian Family Physician, the journal of the College of Family Physicians of Canada:
Top studies of 2023 relevant to primary care | The College of Family Physicians of Canada (cfp.ca)

Ray Clouse Award for best research publication on functional gastrointestinal and motility disorders for 2024, awarded 18/5/2024
Ray Clouse Award – Rome Foundation (theromefoundation.org)