Young woman with stomach pain

(© Hazal -

LEEDS, United Kingdom — An antidepressant can also alleviate symptoms of irritable bowel syndrome (IBS) among patients receiving care from a general practitioner (GP). British researchers conducted the study in primary care settings, where GPs prescribed amitriptyline — whose brand names include Elavil and Vanatrip. Patients adjusted their doses based on the severity of their symptoms using a specialized adjustment document designed for the trial.

The study revealed that patients taking amitriptyline were nearly twice as likely to report an overall improvement in symptoms compared to those taking a placebo.

“Amitriptyline is an effective treatment for IBS and is safe and well tolerated,” says study co-chief investigator Alexander Ford, professor of gastroenterology at the University of Leeds’ School of Medicine, in a university release. “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 affects approximately one in 20 people worldwide, causing abdominal pain and alterations in bowel movements. This long-term condition, which currently lacks a known cure, varies in severity over time and significantly impacts patients’ quality of life, work, and social interactions. Most available treatments have limited efficacy, and patients often experience persistent troublesome symptoms.

Amitriptyline belongs to a group of medications known as tricyclics. Initially used at high doses to treat depression, it is now rarely prescribed for this purpose due to the development of newer treatments.

While earlier small trials suggested potential benefits of low-dose tricyclic antidepressants for IBS in hospital clinic patients with more challenging symptoms, the ATLANTIS trial represents the first randomized controlled trial of low-dose amitriptyline versus a placebo tablet for IBS in primary care. It is also the largest trial of its kind worldwide.

Although GPs already prescribe low-dose amitriptyline for conditions such as chronic nerve pain and migraine prevention, the evidence for its effectiveness in treating IBS has remained uncertain until now.

Man battling stomach pain from possible gastrointestinal disorder
(© Prostock-studio –

Based on the ATLANTIS trial’s results, which demonstrate a clear benefit of amitriptyline, GPs can now offer this low-dose medication to individuals with IBS if their symptoms do not improve with first-line treatments.

“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,” explains study co-chief Investigator Hazel Everitt, professor of primary care research at the University of Southampton.

The ATLANTIS trial enrolled 463 people with IBS from West Yorkshire, Wessex, and the West of England, recruited from 55 general practices. Participants were randomly assigned to either receive amitriptyline or a placebo. They had control over the number of tablets they took, adjusting the dosage based on their IBS symptoms and any side-effects using a patient dose adjustment document created specifically for the trial.

After six months, participants taking amitriptyline reported a significant improvement in their symptom scores compared to those on the placebo. They were nearly twice as likely to report an overall improvement in IBS symptoms, with amitriptyline showing superior results across various IBS symptom measures.

Researchers also monitored participants’ anxiety and depression scores, which remained unchanged. This suggests that the beneficial effects of amitriptyline were primarily related to its impact on the gut rather than any antidepressant properties.

No significant safety concerns were identified, and side-effects in those taking amitriptyline were generally mild, such as experiencing a dry mouth in the morning.

“The results of this study are hugely encouraging,” says Andrew Farmer, director of the National Institute for Health and Care Research’s Health Technology Assessment Program. “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.”

The study is published in the journal The Lancet.

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