Amitriptyline helps relieve IBS symptoms

A cheap and widely available prescription drug can improve symptoms of irritable bowel syndrome in patients seen in GP surgeries, new research presented today at UEG Week 2023 has found. 

Amitriptyline, which is commonly used at low doses for a range of health concerns, has been found to improve irritable bowel syndrome (IBS) symptoms too, according to the results of the ATLANTIS trial. 

Led by researchers at the Universities of Leeds, Southampton, and Bristol and funded by the National Institute for Health and Care Research (NIHR), the study was conducted in primary care. GPs prescribed the drug and patients managed their own dose based on the severity of their symptoms, using an adjustment document designed for the trial. Most people with IBS are seen and managed in primary care by their GP, which means that the results of this trial are likely to be applicable to many people with the condition. 

The results, published today in The Lancet, showed that patients taking amitriptyline were almost twice as likely to report an overall improvement in symptoms as those taking a placebo. 

Now the trial team is recommending that GPs support their patients with IBS to use amitriptyline to manage their symptoms – and has made the dose adjustment document available for clinicians and patients. 

Co-chief Investigator Alexander Ford, Professor of Gastroenterology in the University of Leeds’s School of Medicine, said: “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.” 

IBS, which affects around 1 in 20 people worldwide, causes abdominal pain and changes to bowel movements. The long-term condition, which has no known cure, fluctuates in severity over time. It can have a substantial impact on quality of life and ability to work and socialise. Most treatments only have a modest effect and people often have ongoing troublesome symptoms. 

Amitriptyline belongs to a group of medications called tricyclics. Originally used at high doses to treat depression, today these are rarely used for this condition because newer treatments have been developed.  

Previous small trials of low-dose tricyclic antidepressants for IBS suggested a possible benefit in patients seen in hospital clinics, who often have more difficult to treat symptoms, but this new study is the first randomised controlled trial of low-dose amitriptyline versus a placebo tablet for IBS in primary care. It is also the largest trial of amitriptyline for IBS undertaken worldwide. 

GPs already prescribe low-dose amitriptyline to treat chronic nerve and back pain, and to help prevent migraine attacks. NICE guidelines currently state that GPs could consider using a low dose tricyclic, like amitriptyline, for IBS but, until now, the evidence for a benefit has been uncertain. 

Based on the results of the trial, which showed a clear benefit of amitriptyline, GPs can offer low-dose amitriptyline to people with IBS as part of shared decision making if symptoms don't improve with first-line treatments.   

Co-chief Investigator Hazel Everitt, Professor of Primary Care Research at the Primary Care Research Centre, University of Southampton, said: “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.’’ 

The ATLANTIS trial was funded by the NIHR Heath Technology Assessment programme. Some 463 people with IBS took part from three regions across the UK - West Yorkshire, Wessex, and West of England. They were recruited from 55 general practices.  

Participants were put at random into two groups – those receiving amitriptyline and those receiving a placebo. Participants controlled how many tablets of the trial medication they took, receiving support via the patient dose adjustment document that was developed with patient representatives especially for this trial. This enabled participants to increase or decrease the number of tablets based on their IBS symptoms and any side effects experienced.  

Participants taking amitriptyline reported a bigger improvement in their symptom scores after six months compared with those taking a placebo. Those taking amitriptyline were almost twice as likely as those taking a placebo to report an overall improvement in IBS symptoms, with amitriptyline performing better across a wide range of IBS symptom measures. 

Researchers monitored participants’ anxiety or depression scores and found that they were not altered – suggesting that the beneficial effects of the medication were via the gut, not because of any effect as an antidepressant. 

No safety concerns were identified and side effects in people on amitriptyline were mostly mild, such as a dry mouth in the morning. 

Matthew Ridd, GP and Professor of Primary Health Care at the Centre for Academic Primary Care, University of Bristol, said: “Pragmatic trials like this are always challenging to do in primary care and the team worked hard to overcome the additional challenges of 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, said: “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 big effect over a placebo is significant because it can help improve the quality of life of patients with this condition.” 

Professor Andrew Farmer, Director NIHR's Health Technology Assessment (HTA) Programme, said: "The results of this study are hugely encouraging. It shows that a drug already widely available to treat a number of other conditions appears to be safe and effective for people with IBS. The findings the research team have shared around the adjustment of dosages can be tremendously helpful to GPs in guiding them when treating patients. 

“IBS affects a significant number of people in the UK and can have a debilitating effect on their day-to-day lives. This is another excellent example of how high-quality research can lead to positive changes in health and social care practice and treatments for the benefit of patients and healthcare professionals.” 

Further information 

IBS scores were measured using the IBS-SSS scale. Amitriptyline participants scored a 99-point improvement compared with a 69-point improvement among placebo participants. 

“Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome as Second-line Treatment (ATLANTIS): A Randomised Double-blind Placebo-controlled Trial in Primary Care” is published in The Lancet at 23:01 UK time on 16 October 2023 and is presented at the UEG Week conference. 

For media enquiries, contact University of Leeds press officer Lauren Ballinger via l.ballinger@leeds.ac.uk. 

University of Leeds 
The University of Leeds is one of the largest higher education institutions in the UK, with more than 38,000 students from more than 150 different countries, and a member of the Russell Group of research-intensive universities. The University plays a significant role in the Turing, Rosalind Franklin and Royce Institutes. 
We are a top ten university for research and impact power in the UK, according to the 2014 Research Excellence Framework, and are in the top 100 of the QS World University Rankings 2021.  
The University was awarded a Gold rating by the Government’s Teaching Excellence Framework in 2017, recognising its ‘consistently outstanding’ teaching and learning provision. Twenty-six of our academics have been awarded National Teaching Fellowships – more than any other institution in England, Northern Ireland and Wales – reflecting the excellence of our teaching. www.leeds.ac.uk  
Follow University of Leeds or tag us in to coverage: Twitter Facebook LinkedIn Instagram 

University of Southampton 
The University of Southampton drives original thinking, turns knowledge into action and impact, and creates solutions to the world’s challenges. We are among the top 100 institutions globally (QS World University Rankings 2024). Our academics are leaders in their fields, forging links with high-profile international businesses and organisations, and inspiring a 22,000-strong community of exceptional students, from over 135 countries worldwide. Through our high-quality education, the University helps students on a journey of discovery to realise their potential and join our global network of over 200,000 alumni. www.southampton.ac.uk 

University of Bristol 
The Centre for Academic Primary Care (CAPC) is a leading centre for primary care research and teaching in the UK, and one of nine centres that form the NIHR School for Primary Care Research. It is part of Bristol Medical School, an internationally recognised centre of excellence for population health sciences research and teaching.  
The University is ranked within the top 10 universities in the UK and 55th in the world (QS World University Rankings 2024); it is also ranked among the top five institutions in the UK for its research, according to analysis of the Research Excellence Framework (REF) 2021; and is the 4th most targeted university by top UK employers. 
The University was founded in 1876 and was granted its Royal Charter in 1909.  It was the first university in England to admit women on the same basis as men.  
The University is a major force in the economic, social and cultural life of Bristol and the region, but is also a significant player on the world stage. It has over 20,000 undergraduates and over 7,000 postgraduate students from more than 150 countries, and its research links span the globe. 

The National Institute for Health and Care Research (NIHR)  
The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by: Funding high quality, timely research that benefits the NHS, public health and social care; 

1. Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services; 

1. Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research; 

1. Attracting, training and supporting the best researchers to tackle complex health and social care challenges; 

1. Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system; 

1. Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries. 
    
   NIHR is funded by the Department of Health and Social Care. Its work in low- and middle-income countries is principally funded through UK Aid from the UK government.