A new study conducted by the universities of Leeds, Southampton, and Bristol has unveiled the significant potential of amitriptyline in alleviating the symptoms of IBS.

The findings from the ATLANTIS trial, the most extensive examination of a tricyclic antidepressant’s role in IBS to date, offers compelling evidence to prompt revisions in current guidelines.

The researchers, including The IBS Network’s Professor Alex Ford, underscored the importance of incorporating the results of the ATLANTIS trial into existing recommendations. Presently, the National Institute for Health and Care Excellence (NICE) guideline on IBS advises considering low-dose tricyclic antidepressants as a second-line treatment in primary care settings—where a majority of IBS patients receive care—particularly when initial therapies prove ineffective.

Historically, most trials examining the efficacy of tricyclic antidepressants for IBS have taken place in specialised medical environments, focusing on patients with more severe symptoms. However, their effectiveness in primary care remains largely uncharted.

Notably, tricyclic antidepressants are rarely prescribed for IBS in this context. The researchers noted that less than 10% of general practitioners (GPs) currently recommend tricyclic antidepressants for IBS, in stark contrast to the 95% who do so for insomnia. This discrepancy implies a hesitancy rooted in uncertainties about the drug’s effectiveness in treating IBS, rather than concerns over potential side effects.

NICE itself had recognised the need for a trial evaluating the use of tricyclic antidepressants in IBS within primary care. Consequently, the researchers embarked on the ATLANTIS trial, a rigorous randomised, double-blind, placebo-controlled study.

This trial involved 463 IBS patients (with a mean age of 48.5 years and 68% being female) from 55 general practices across England. Participants were randomly assigned to receive a low dose of amitriptyline, 10 mg once daily, or a placebo for a period of six months, with subsequent dose adjustments (up to 30 mg once daily) facilitated by patients themselves over a 3-week period, based on their symptoms and tolerance.

The published findings, which were also presented at UEG (United European Gastroenterology) Week 2023 in Copenhagen, reveal a noteworthy development: patients who were prescribed amitriptyline experienced a remarkable doubling of symptom severity improvement in comparison to those who received a placebo.

Interestingly, anxiety or depression scores of participants remained unaltered during the study, indicating that the advantageous effects of amitriptyline were primarily related to the gut and not attributable to its role as an antidepressant. This distinction is of vital importance in understanding the mechanism behind the treatment’s success.

Alexander Ford, professor of gastroenterology at the University of Leeds School of Medicine and co-chief investigator, 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.”