ATLANTIS study (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment)

ATLANTIS study (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment)

• ATLANTIS study (Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment) assessed the clinical effectiveness of low-dose amitriptyline (10-30mg) for adults with IBS in primary care in a randomised, double-blind, placebo-controlled trial
  • eligible participants were aged 18 years or over with IBS of any subtype, ongoing symptoms despite dietary changes and first-line therapies, and no contraindications to amitriptyline
    • had a normal full blood count and C-reactive protein, negative coeliac serology, and no evidence of suicidal ideation
  • 463 participants from general practice were randomised to low-dose oral amitriptyline or placebo for 6 months, with participant-led dose titration over 3 weeks (10mg to 30mg once daily), according to symptoms and tolerability
    
    
• study results:
  • for the primary outcome, the trial found a significant difference in favour of amitriptyline in the IBS Symptom Severity Score (IBS-SSS) at 6 months (-27.0; 95% CI -46.9 to -7.10, p=0.008)
  • amitriptyline was superior to placebo across other secondary endpoints, including subjective global assessment of relief of IBS symptoms at 6 months, but had no impact on anxiety or depression scores
    • participants' anxiety or depression scores were not altered, suggesting that the beneficial effects of amitriptyline were gut-mediated and not because of any effect as an antidepressant per se
  • most adverse events with amitriptyline were mild and consistent with its known anticholinergic effects
    
    
• study authors concluded:
  • ".. Amitriptyline was more effective than placebo across a range of IBS symptom measures, and was safe and well tolerated, when titrated according to symptom response and side-effects. When the rationale for use of a tricyclic antidepressant for IBS is explained clearly, as in the information materials provided to participants in this trial, with appropriate support, many people with IBS find it acceptable and beneficial. General practitioners should offer low-dose amitriptyline to patients with IBS in whom first-line therapies are ineffective, with appropriate support to guide patient-led dose titration, such as the self-titration document we developed.."

General practitioners should offer low-dose amitriptyline to patients with irritable bowel syndrome whose symptoms do not improve with first-line therapies (2):

• guidance and resources should support GP–patient communication to distinguish amitriptyline for irritable bowel syndrome from use as an antidepressant and to support patients managing their own dose titration

Contributor:

• Professor Robert Foy - Leeds Institute of Health Sciences, School of Medicine, University of Leeds, Leeds, UK

Reference:

1. Ford AC et al. Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment in primary care (ATLANTIS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet October 16th 2023.
2. Wright-Hughes A, Ford AC, Alderson SL, Ow PL, Ridd MJ, Foy R, et al. Low-dose titrated amitriptyline as second-line treatment for adults with irritable bowel syndrome in primary care: the ATLANTIS RCT. Health Technol Assess 2024;28(66)