The ATLANTIS trial, led by researchers at the Universities of Bristol, Southampton, and Leeds, and published in The Lancet, was funded by the National Institute for Health and Care Research (NIHR).
The RCGP Research Paper of the Year Award will be presented at the annual RCGP Conference today [3 October]. The award recognises and celebrates an individual or group of researchers who have undertaken and published an exceptional piece of research relating to general practice or primary care.
The ATLANTIS trial showed that people with IBS taking low dose amitriptyline were almost twice as likely to report an overall improvement in their IBS symptoms to those taking a placebo. Amitriptyline, already prescribed at low dose for a range of other health conditions, was also more acceptable to participants than placebo and performed better across a wide range of IBS symptom measures.
The ATLANTIS results are widely applicable to the majority people with IBS as most have their condition managed in primary care by their GP.
During the trial participants managed 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, available here. This enabled participants to increase or decrease the number of tablets based on their IBS symptoms and any side effects experienced.
Hazel Everitt, Professor of Primary Care Research at the Primary Care Research Centre at the University of Southampton, and co-chief investigator, said: “We are delighted that our research has received this prestigious Royal College award. Prior to ATLANTIS, GPs rarely prescribed amitriptyline for IBS as the research evidence was uncertain, but the ATLANTIS trial has provided good evidence of benefit. The award will help raise awareness of low dose amitriptyline as an option for GPs to offer to people with IBS. To support this we have made available the document participants used during the trial to self-adjust their medication dose depending on symptoms and side effects.”
Matthew Ridd, GP and Professor of Primary Health Care from the Centre for Academic Primary Care at the University of Bristol, who led the the Bristol arm of the trial, added: “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.”
Alexander Ford, Professor of Gastroenterology in the University of Leeds’s School of Medicine, and co-chief Investigator, explained: “Amitriptyline is an effective treatment for IBS and is safe and well tolerated. This 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.”
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.”
IBS, affects about 1 in 20 people worldwide, causing abdominal pain and changes to bowel movements. It is a long-term condition, with no known cure, which can fluctuate in severity over time and have a substantial impact on quality of life and ability to work and socialise. Most current treatments only have a modest effect and people often have ongoing troublesome IBS symptoms for many years.
Amitriptyline belongs to a group of medications called tricyclics. Originally used at high doses to treat depression, today these are rarely used for depression 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, but ATLANTIS was 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. In the ATLANTIS trial, 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 an identical placebo. Participants taking amitriptyline reported a bigger improvement in their symptom scores after six months compared with those taking a placebo. 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 taking amitriptyline were mostly mild, such as a dry mouth in the morning.
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. Now there is high quality evidence that it can be beneficial the ATLANTIS researchers are encouraging wider use of amitriptyline for IBS in primary care.
Paper
'Amitriptyline at low-dose and titrated for irritable bowel syndrome as second-line treatment in primary care (ATLANTIS): a randomised, double-blind, placebocontrolled, phase 3 trial' is by Alexander C Ford, Alexandra Wright-Hughes, Matthew J Ridd, Amanda J Farrin, Hazel A Everitt et al. in The Lancet [open access]