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This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.

Researchers evaluated whether a low dose of amitriptyline, a common antidepressant medicine, improved irritable bowel syndrome (IBS) in people who had already tried first-line treatments.

They found that, after 6 months:

• overall symptoms and abdominal pain improved more in people taking low-dose amitriptyline than in those taking placebo (dummy pills)
• low-dose amitriptyline was safe, and well tolerated.

This new high-quality evidence will inform GPs and people with IBS about use of low-dose amitriptyline for IBS.

More information about IBS can be found on the NHS website.

Is amitriptyline effective for IBS?

People with irritable bowel syndrome (IBS) frequently have abdominal pain with constipation and/or diarrhoea. IBS is common. Symptoms may come and go but are commonly long-term, and impact quality of life.

IBS is usually managed in primary care. First-line treatments include dietary changes and medicines (for constipation, diarrhoea, and abdominal spasms) but they are not always effective. In National Institute for Health and Care Excellence (NICE) guidelines, a next potential step is to consider a low-dose of an antidepressant medicine, such as amitriptyline. Before this study, there was limited research evidence on amitriptyline for IBS and GPs did not prescribe it often.

The ATLANTIS research trial compared low-dose amitriptyline with placebo (dummy pills) in people with IBS whose symptoms had not improved with first-line treatments.

What’s new?

Conducted between 2019 and 2022, the ATLANTIS study recruited people with IBS from 55 general practices in England. Most had moderate to severe symptoms of irritable bowel syndrome (IBS). Participants were aged 49 years on average; most (68%) were female.

In this randomised controlled trial, half the participants (232) took low-dose amitriptyline (10mg per tablet) and the other participants (231) took an identical placebo tablet for 6 months. They all received an information leaflet to help them manage their dose (starting at one tablet each evening and increasing to two or three tablets depending on their symptoms and side effects). Participants continued to receive usual care for IBS from their GP (such as dietary advice). 338 participants completed 6 months of treatment: 173 (75%) in the amitriptyline group and 165 (71%) in the placebo group.

To compare the groups, the researchers used the IBS severity scoring system (IBS-SSS). A score of 75-174 indicates mild symptoms; 175-299 moderate symptoms; 300+ severe symptoms.

The primary outcome of the study at 6 months showed:

  • people in the amitriptyline group reported greater improvements in IBS symptoms (their average IBS-SSS score improved by 99 points compared with 69 points for people in the placebo group).

Secondary outcomes showed that people in the amitriptyline group:

  • were more likely to report relief of their IBS symptoms (61% participants) compared with those taking placebo (45%)
  • were more likely to find their treatment acceptable (58% participants) compared with those taking placebo (47%)
  • had similar anxiety, depression and work and social adjustment scores (ability to work and take part in other activities) to people in the placebo group
  • were less likely to discontinue treatment during the trial (20% participants) compared with the placebo group (26%).

People in the amitriptyline group experienced more dry mouth and drowsiness side effects but less insomnia than the placebo group. Few serious adverse events occurred in either group (2 in the amitriptyline group; 3 in the placebo group).

At 3 months, similar numbers in each group said they were still taking the pills as prescribed. By 6 months, more were still taking amitriptyline (74%) than placebo (68%).

Why is this important?

The researchers say this is the largest trial of a tricyclic antidepressant in IBS to date. The findings suggest that low-dose amitriptyline reduces the severity of IBS symptoms and is safe and well tolerated.

The results will inform shared decision-making and provide GPs and people with IBS information to try low-dose amitriptyline if first-line options have not been effective.

The researchers have developed guidance to help people with IBS manage their amitriptyline dose.

What’s next?

The researchers hope their findings will inform the next update on NICE guidelines for treatment of IBS.

You may be interested to read

This is a summary of: Ford AC, and others. 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. The Lancet 2023; 402: 1773 – 1785.

The ATLANTIS homepage carries information for GPs and patients on the research and how to manage the dose.

Guts UK offers advice and support for people suffering from IBS and other conditions of the digestive system.

The IBS Network offers advice and support for people suffering from IBS.

A podcast in which one of the study authors explains the findings.

Article in the Daily Mail about the findings.

The researchers held a webinar on 30 January 2024 to explain the study and findings to patients.

Funding: This study was funded by the NIHR Health Technology Assessment Programme.

Conflicts of Interest: Several of the study authors have received funding from charities. See paper for full details.

Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.

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