Image description: The picture shows a group of yellow Amitriptyline tablets. The title reads Amitriptyline nearly doubles IBS symptom improvement. ME Association logo bottom right

Research: Amitriptyline nearly doubles IBS symptom improvement

Amitriptyline, titrated at low dose, was superior to placebo as a second-line treatment for irritable bowel syndrome (IBS) across multiple outcomes in what the researchers call the largest randomized controlled trial (RCT) of a tricyclic antidepressant in the condition.

ME Association Comment

The use of amitriptyline, a drug that is normally used to treat depression, as a possible management option for symptom relief in irritable bowel syndrome (IBS) is already well recognised. This is especially so where diarrhoea and abdominal pain are the main symptoms but amitriptyline can also be helpful for painful bloating and nausea. 

Low dose amitriptyline is also a management option for pain and sleep disturbance in ME/CFS that some (but not all) people with ME/CFS find helpful.

This is a large and interesting study, the results of which indicate that low dose amitriptyline may be more helpful in the overall management of IBS than was previously recognised.

  • If you are being, or have been, prescribed amitriptyline for IBS symptoms as part of ME/CFS please let us know how effective it was.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.

Dr Charles Shepherd

By Becky McCall, Medscape, RCGP Conference News, 19 October 2023.

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) trialLow-dose amitriptyline appeared safe and well tolerated, they reported…

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, Everitt told Medscape Medical News. “GPs haven't often prescribed amitriptyline for IBS ― probably because of the lack of research evidence for its use in primary care.”

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.”

The Research


Most patients with irritable bowel syndrome (IBS) are managed in primary care. When first-line therapies for IBS are ineffective, the UK National Institute for Health and Care Excellence guideline suggests considering low- dose tricyclic antidepressants as second-line treatment, but their effectiveness in primary care is unknown, and they are infrequently prescribed in this setting.


To our knowledge, this is the largest trial of a tricyclic antidepressant in IBS ever conducted. Titrated low-dose amitriptyline was superior to placebo as a second-line treatment for IBS in primary care across multiple outcomes, and was safe and well tolerated. General practitioners 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, such as the self-titration document developed for this trial.

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