A multicenter, double-blind, placebo-controlled trial was conducted to determine if amitriptyline (10-30 mg nightly) is superior to placebo for improving irritable bowel syndrome (IBS) symptoms over 6 months in the primary care setting. The study included 463 patients who met the Rome IV criteria for IBS, with a baseline IBS-Symptom Severity Score (IBS-SSS) greater than 75. Patients were randomized to receive amitriptyline or a placebo, with the option to titrate the dose based on symptom improvement. The primary outcome was the change in IBS-SSS after 6 months, with a secondary outcome assessing global relief of IBS symptoms.

Results showed that amitriptyline significantly improved IBS symptoms, with the IBS-SSS score decreasing by an average of 27 points compared to 8 points for the placebo group (P = 0.008). Amitriptyline-treated patients were also more likely to report relief of IBS symptoms (odds ratio 1.78 for some relief, 1.88 for considerable/complete relief). Adverse events, primarily due to the drug’s anticholinergic effects, occurred more frequently in the amitriptyline group, with dry mouth, drowsiness, and blurred vision being the most common. Despite these side effects, amitriptyline was found to be effective in improving IBS symptoms in the primary care setting.

Reference: Schoenfeld P. Low-dose Tricyclic Antidepressants for Irritable Bowel Syndrome: Definitive Evidence of Benefit from ATLANTIS. American College of Gastroenterology. Published December 12, 2023. Accessed February 7, 2025. https://gi.org/journals-publications/ebgi/schoenfeld_dec2023/