GLASGOW – in what the researchers call the largest randomized controlled trial (RCT) of a tricyclic antidepressant in the condition.
Patients who took low-dose amitriptyline were almost twice as likely to report an overall improvement in symptoms as those taking placebo, according to investigators of the Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS) trial. Low-dose amitriptyline appeared safe and well tolerated, they reported.
Hazel Everitt, PhD, professor of primary care research at the University of Southampton, England, presented the findings at the annual conference of the Royal College of General Practitioners.
The data were also published in The Lancet and were presented at the recent United European Gastroenterology Week 2023.
Clinicians “should offer low-dose amitriptyline to patients with IBS whose symptoms do not improve with first-line therapies, with appropriate support to guide patient-led dose titration,” the researchers wrote in the journal article.
Despite first-line treatments such as diet, fiber, and antispasmodics, many patients with IBS continue to have troublesome symptoms, Dr. Everitt said in an interview. “GPs haven’t often prescribed amitriptyline for IBS – probably because of the lack of research evidence for its use in primary care.”
Dr. Everitt added that primary care physicians and patients interviewed for the study welcomed low-dose amitriptyline as a potential additional option, especially with increased patient-led care. “The dose titration document that was developed with patients specifically for the trial enables patients to be more empowered to manage their IBS by helping them to titrate their dose up or down depending on their symptoms and side effects.”
Judith Danby, MBBS, a retired GP who moderated the session at which the ATLANTIS results were presented, said, “Self-titration of the dose equals patient empowerment, and if patients can be helped to manage their own medication, then they will also be more empowered to think about lifestyle change, too.”
RCT across 55 practices
The U.K.’s National Institute for Health and Care Excellence guidance for the management of IBS in primary care says clinicians should “consider” using low-dose tricyclic antidepressants as a second-line treatment but highlight the need for an RCT of these drugs carried out solely in primary care.
The ATLANTIS trial was conducted across 55 general practices in England and included adults with Rome IV IBS of any subtype and ongoing symptoms (IBS Severity Scoring System [IBS-SSS] score ≥ 75 points) despite dietary changes and first-line therapies. Participants had normal full blood counts and C-reactive protein measures, negative celiac serology, and no evidence of suicidal ideation. The mean age was 48.5 years, and 68% were female. The mean IBS-SSS score in all participants was 272.8 at baseline.
Patients were randomly assigned in a 1:1 ratio to receive either low-dose oral amitriptyline (10 mg once daily; n = 232) with dose titration over 3 weeks (up to a maximum dose of 30 mg once daily) as determined by a participant’s symptoms and tolerability; or placebo (n = 231). Both groups participated for 6 months. The primary outcome was the IBS-SSS score at 6 months.