Research from the ATLANTIS trial presented at UEG Week 2023 suggests that amitriptyline, a common drug, may effectively alleviate symptoms of irritable bowel syndrome (IBS), providing a new treatment option for patients.
Exciting findings from a recent study indicate that amitriptyline, a widely available and inexpensive prescription drug, has the potential to improve the symptoms of irritable bowel syndrome (IBS) in patients seen in general practitioner (GP) surgeries. The results of the study were presented at UEG Week 2023, a conference organized by the European Society of Gastrointestinal Endoscopy.
The ATLANTIS Trial: A Breakthrough for IBS Treatment
Researchers from the Universities of Leeds, Southampton, and Bristol conducted the ATLANTIS trial, funded by the National Institute for Health and Care Research (NIHR). The study was carried out in primary care, with GPs prescribing amitriptyline to patients who then managed their dosage based on the severity of their symptoms, using a specially designed adjustment document for the trial. As most patients with IBS receive treatment in primary care, the results of this trial are likely applicable to a wide range of individuals with the condition.
Positive Results Published in The Lancet
The results, published in The Lancet, demonstrated that patients who took amitriptyline were nearly twice as likely to report an overall improvement in symptoms compared to those who took a placebo. Based on these promising findings, the trial team recommends that GPs support their IBS patients in using amitriptyline to manage their symptoms. The dose adjustment document developed for the trial is now available for clinicians and patients.
Insights from Experts:
Co-chief Investigator Alexander Ford, a Professor of Gastroenterology at the University of Leeds’s School of Medicine, states that “Amitriptyline is an effective treatment for IBS and is safe and well tolerated. This new rigorously conducted research indicates that general practitioners should support patients in primary care to try low-dose amitriptyline if their IBS symptoms haven’t improved with recommended first-line treatments.”
Understanding IBS and Amitriptyline
IBS is a prevalent condition affecting approximately 1 in 20 people worldwide. It is characterized by abdominal pain and changes in bowel movements and has no known cure. Symptoms can vary in severity over time, significantly impacting an individual’s quality of life and daily functioning. Most currently available treatments have only modest effects, leaving many individuals with ongoing troublesome symptoms.
Amitriptyline belongs to a group of medications called tricyclic antidepressants. While it was originally used at higher doses to treat depression, it is now less commonly prescribed for this purpose due to the development of newer treatments. Small-scale trials on low-dose tricyclic antidepressants for IBS have suggested potential benefits for patients seen in hospital clinics, particularly those with more challenging symptoms. However, the ATLANTIS trial is the first randomized controlled trial of low-dose amitriptyline versus a placebo tablet for IBS in primary care, making it the largest trial of its kind worldwide.
Supporting Evidence and Recommendations
GPs already prescribe low-dose amitriptyline to manage chronic nerve and back pain and prevent migraines. Current guidelines from the National Institute for Health and Care Excellence (NICE) suggest that GPs may consider using a low-dose tricyclic antidepressant like amitriptyline for IBS. However, until now, the evidence supporting this recommendation has been uncertain. The clear benefits of amitriptyline demonstrated in the ATLANTIS trial allow GPs to confidently offer this treatment option to IBS patients who do not respond to first-line treatments, incorporating shared decision-making.
Co-chief Investigator Hazel Everitt, a Professor of Primary Care Research at the Primary Care Research Centre, University of Southampton, explains, “Prior to ATLANTIS, GPs haven’t often prescribed amitriptyline for IBS as the research evidence was uncertain, but our new research provides good evidence of benefit. GPs already prescribe low-dose amitriptyline for other conditions, such as chronic pain and poor sleep, and when we interviewed GPs as part of this research, they were willing to prescribe it for IBS if the research evidence supported this. Participants were also keen to have another option to try to help their IBS symptoms and most were happy to self-adjust their dose depending on symptoms and side effects.”
Participants and Key Findings
Funded by the NIHR Heath Technology Assessment program, the ATLANTIS trial involved 463 IBS patients recruited from 55 general practices in three UK regions—West Yorkshire, Wessex, and West of England. Participants were randomly assigned to receive either amitriptyline or a placebo. Using a patient dose adjustment document developed specifically for the trial, participants had control over the number of trial medication tablets they consumed, allowing them to increase or decrease their dosage based on IBS symptoms and any side effects experienced.
After six months, participants taking amitriptyline reported significantly greater improvements in their symptom scores compared to those taking a placebo. They were almost twice as likely to report an overall improvement in IBS symptoms. Amitriptyline exhibited better performance across various measures of IBS symptoms. Importantly, participants’ anxiety or depression scores remained unchanged throughout the trial, suggesting that the beneficial effects of the medication were solely related to its impact on the gut, rather than its potential as an antidepressant. No safety concerns were identified, and the most commonly reported side effect in amitriptyline users was a mild dry mouth in the morning.
Expert Opinions and Additional Information
Matthew Ridd, a GP and Professor of Primary Health Care at the Centre for Academic Primary Care, University of Bristol, commended the study, stating, “Pragmatic trials like this are always challenging to conduct in primary care, and the team worked hard to overcome the additional challenges posed by the Covid-19 pandemic. It’s fantastic that we’ve found that amitriptyline is an effective and safe option for patients with IBS to try.”
Amanda Farrin, Professor of Clinical Trials and Evaluation of Complex Interventions, who leads the Complex Intervention Division of the Leeds Clinical Trials Research Unit, adds, “The participants in the ATLANTIS trial had moderate to severe symptoms and an average duration of IBS of 10 years. The fact that amitriptyline had such a significant effect compared to a placebo is particularly significant because it can improve the quality of life for patients with this condition.”
In Conclusion
Professor Andrew Farmer, Director of the NIHR’s Health Technology Assessment (HTA) Programme, expresses enthusiasm for the study’s results, stating, “The results of this study are hugely encouraging. They demonstrate that a widely available drug used to treat various conditions appears to be both safe and effective for individuals with IBS. The dosage adjustment findings shared by the research team will greatly assist GPs in treating their patients. IBS affects a significant number of people in the UK and can severely impact their daily lives. This is yet another example of how high-quality research can lead to positive changes in health and social care, benefitting patients and healthcare professionals alike.”
For More Information
The severity of IBS symptoms was measured using the IBS-SSS scale. Participants taking amitriptyline demonstrated a 99-point improvement, compared to a 69-point improvement among those taking a placebo.
Reference: “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” by Alexander C Ford, Alexandra Wright-Hughes, Sarah L Alderson, Pei-Loo Ow, Matthew J Ridd, Robbie Foy, Gina Bianco, Felicity L Bishop, Matthew Chaddock, Heather Cook, Deborah Cooper, Catherine Fernandez, Elspeth A Guthrie, Suzanne Hartley, Amy Herbert, Daniel Howdon, Delia P Muir, Taposhi Nath, Sonia Newman, Thomas Smith, Christopher A Taylor, Emma J Teasdale, Ruth Thornton, Amanda J Farrin, Hazel A Everitt, Alexander C. Ford, Alex Wright-Hughes, Sarah L. Alderson, Pei-Loo Ow, Matthew J. Ridd, Robbie Foy, Maggie Barratt, Gina Bianco, Felicity L. Bishop, Richard Brindle, Sarah Brown, Matthew Chaddock, Aimee Christodoulou, Heather Cook, Deborah Cooper, Florence Day, Aaron Dowse, Jill Durnell, Jake Emmerson, Alasdair Fellows, Catherine Fernandez, Elspeth A. Guthrie, Suzanne Hartley, Amy Herbert, Damien Hindmarch, Daniel Howdon, Aminah Malik, Tom Morris, Delia P. Muir, Roberta Longo, Sandra Lopes Goncalves Graca, Taposhi Nath, Sonia Newman, Catriona Parker, Thomas Smith, Christopher A. Taylor, Emma J. Teasdale, Ruth Thornton, Sandy Tubeuf, Amy West, Emma-Jane Williamson, Amanda J. Farrin and Hazel A. Everitt, 16 October 2023, The Lancet.
DOI: 10.1016/S0140-6736(23)01523-4
