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

Neurogastroenterol Motil. 2012 Sep;24(9):860-e398. doi: 10.1111/j.1365-2982.2012.01945.x. Epub 2012 Jun 11.


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 (P<0.05).

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

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amitriptyline / adverse effects
  • Amitriptyline / therapeutic use*
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Diarrhea / drug therapy*
  • Diarrhea / etiology
  • Female
  • Humans
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / drug therapy*
  • Male
  • Middle Aged
  • Probiotics / therapeutic use
  • Thiazepines / adverse effects
  • Thiazepines / therapeutic use*
  • Treatment Outcome


  • Antidepressive Agents, Tricyclic
  • Thiazepines
  • tianeptine
  • Amitriptyline