Tianeptine vs amitriptyline for the treatment of irritable bowel syndrome with diarrhea: a multicenter, open-label, non-inferiority, randomized controlled study

Authors


Address for Correspondence
Oh Young Lee, MD, PhD, Department of Internal Medicine, Hanyang University College of Medicine, 17 Haengdang-dong Sungdong-gu, Seoul 133-792, Korea.
Tel: +82 2 2290 8343; fax: +82 2 972 0068;
e-mail: leeoy@hanyang.ac.kr

Abstract

Background  Tricyclic antidepressants have good efficacy in irritable bowel syndrome with diarrhea (IBS-D), but their clinical use is limited by considerations of tolerability. Tianeptine, another antidepressant, acts as a selective serotonin reuptake enhancer. We compared tianeptine with amitriptyline for the treatment of patients with IBS-D.

Methods  We undertook a multicenter, randomized, open-label, non-inferiority clinical study that compared tianeptine with amitriptyline, each in combination with probiotics, for the treatment of IBS-D. Subjects were randomized to receive tianeptine (37.5 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) or amitriptyline (10 mg)/probiotics (Bacillus subtilis + Streptococcus faecium) for 4 weeks. A total of 228 patients were analyzed by the intention-to-treat approach. The primary efficacy endpoint was the proportion of patients who had global relief of IBS symptoms at week 4. The secondary efficacy endpoints were intensity of abdominal pain/discomfort, stool frequency/consistency, quality of life, and overall satisfaction with treatment.

Key Results  At week 4, non-inferiority of the tianeptine group to the amitriptyline group (treatment difference −15.1%; 95% CI −26.6% to −3.8%) was shown, with 81.1% (99 of 122 patients) of the patients in the tianeptine group and 66.0% (70 of 106 patients) in the amitriptyline group reporting global relief of IBS symptoms. The secondary endpoints also demonstrated non-inferiority of the tianeptine group to the amitriptyline group. Adverse events such as dry mouth and constipation were significantly lower in the tianeptine group than the amitriptyline group (< 0.05).

Conclusions & Inferences  Tianeptine is not inferior to amitriptyline for treating IBS-D in terms of both efficacy and tolerability.

Ancillary