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


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
Tianeptine is not inferior to amitriptyline for treating IBS-D in terms of both efficacy and tolerability.
Departments of Gastroenterology, Hanyang University School of Medicine, Seoul, Korea.
W
W
Sohn
O Y
OY
Lee
J G
JG
Kwon
K S
KS
Park
Y J
YJ
Lim
T H
TH
Kim
S W
SW
Jung
J I
JI
Kim
D000328:Adult; D000368:Aged; D000639:Amitriptyline / Q000009:adverse effects / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D019936:Probiotics / Q000627:therapeutic use; D013841:Thiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000929:Antidepressive Agents, Tricyclic; D013841:Thiazepines; C050504:tianeptine; D000639:Amitriptyline