Amitriptyline at Low-dose and Titrated for Irritable Bowel Syndrome in Primary Care: ATLANTIS: Randomised Controlled Trial

• DOI: 10.1370/afm.22.s1.4721
• Publication Date: 2023-11-16T14:55:51Z
• Authors: Hazel Everitt; Robbie Foy; Matthew Ridd; Sarah Alderson; Ruth Thornton; Sonia Newman; Emma Teasdale; Heather Cook; deborah cooper; Catherine Fernandez; Amy Herbert; Matthew Chaddock; Alexandra Wright-...; Amanda Farrin; Suzanne Hartley; Alexander Ford; Felicity Bishop; Pei Loo Ow
• Keywords: Tolerability; Clinical endpoint

<h3>Context:</h3> Most patients with irritable bowel syndrome (IBS) are managed in primary care. If first-line therapies ineffective, UK NICE Guidelines suggests considering low dose tricyclic antidepressants (TCAs), but effectiveness care is unknown and TCA infrequently prescribed for IBS this setting. <h3>Objective:</h3> To determine the clinical of amitriptyline (10-30mg) adults <h3>Study Design Analysis:</h3> Randomised, double-blind, placebo-controlled trial. Participants, clinicians, investigators, analysts masked to allocation. Intention treat analyses effectiveness, according treatment receipt safety analyses. Trial Registration ISRCTN48075063. <h3>Setting:</h3> 55 centres. <h3>Population Studied:</h3> Adults ≥18 years Rome IV any subtype, ongoing symptoms despite therapies, a normal full blood count C-reactive protein, negative coeliac serology, no evidence suicidal ideation. <h3>Intervention:</h3> Participants randomised (1:1) 6 months low-dose oral (10-30mg once daily) or identical placebo, participant self-titration tolerability. <h3>Outcome Measures:</h3> Primary key secondary endpoint: IBS-SSS score Subjective Global Assessment (SGA) relief at months. <h3>Results:</h3> 463 (mean age 48.5 yrs (SD 16.1 yrs), 315 (68.0%) female) randomised, December 2019 April 2022, (232) placebo (231). outcome analysis showed significant difference (−27.0; 95% CI −46.9 −7.10, p=0.008) favour amitriptyline. For SGA symptoms, was superior (125/204 (61.3%) vs. 88/195 (45.1%), OR 1.78; 1.19 2.66, p=0.005). Amitriptyline across other endpoints had impact on anxiety depression. 46 (19.8%) discontinued (30 (12.9%) due adverse events) 59 (25.5%) (20 (8.7%) events). 5 serious reactions (2 amitriptyline, placebo) events were unrelated trial medication. <h3>Conclusions:</h3> This largest ever conducted. Titrated multiple safe. physicians should offer whose do not improve therapies.