BACKGROUND AND PURPOSE:

• When first-line treatments for irritable bowel syndrome (IBS) are ineffective, guidelines suggest low-dose tricyclic antidepressants as a second-line treatment
• Despite most IBS cases being managed in primary care, very few primary care practitioners prescribe tricyclic antidepressants for IBS
• Ford et al. (The Lancet, 2023) examines the impact of amitriptyline on IBS at 6 months

METHODS:

• Randomized, double-blind, placebo-controlled trial
  • Amitriptyline at Low-Dose and Titrated for Irritable Bowel Syndrome as Second-Line Treatment (ATLANTIS)
• Participants
  • ≥18 years
  • Rome IV IBS Criteria: Recurrent abdominal pain, on average, at least 1 day per week associated with stool changes
  • Ongoing symptoms despite first-line treatment
  • Normal full blood count and C-reactive protein | Negative celiac serology | No evidence of suicidal ideation
• Interventions
  • Low-dose oral amitriptyline (10 mg once daily) for 6 months
  • Placebo
• Study design
  • Amitriptyline dose titration occurred over 3 weeks (up to 30 mg daily)
  • Participants, their general practitioners, investigators, and  analysis team were all masked to allocation throughout the trial
  • Analysis by intention-to-treat
  • Safety analyses were conducted with all participants who took at least one dose of the trial drug
• Primary outcome
  • IBS- Severity Scoring System (SSS) score at 6 months

RESULTS:

• Low-dose amitriptyline: 232 participants | Placebo: 231
  • Mean age: 48.5 (SD, 16.1) years | Female: 68%
• There was a significant improvement in IBS-SSS score at 6 months among the low-dose amitriptyline
  • Difference: –27.0 (95% CI, –46.9 to –7.10) | P=0.0079
• Discontinuation due to adverse events before 6 months
  • Low-dose amitriptyline: 13% | Placebo: 9%
• There were 5 serious adverse reactions
  • Amitriptyline group: 2 | Placebo: 3

CONCLUSION:

• As a second-line treatment, low-dose amitriptyline, 10 mg to 30 mg daily, significantly improved IBS symptoms at 6 months vs placebo
• Treatment was well-tolerated
• The authors state

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

Management guidelines should be updated to reflect these findings 

Learn More – Primary Sources:

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