Controlling symptoms in irritable bowel syndrome with diarrhea (IBS-D) can be challenging. Studies have suggested a role for serotonin 5-hydroxytryptamine (5-HT₃) receptors and antagonists in the gastrointestinal tract in the pathogenesis of IBS-D. In one study, ramosetron, a 5-HT₃ antagonist, significantly improved stool consistency when compared with placebo in Japanese men (P < .001) [Fukudo S et al. Clin Gastroenterol Hepatol. 2014]. Of note, ramosetron is not FDA approved.

Shin Fukudo, MD, PhD, Tohoku University Graduate School of Medicine, Sendai, Japan, presented the results of a double-blind placebo-controlled phase 3 trial designed to determine the effects of ramosetron vs placebo in women with IBS-D and to assess adverse events (AEs) [NCT01736423]. Women with IBS-D were randomly assigned to oral ramosetron 2.5 µg (n = 292) or placebo (n = 284) once a day before breakfast for 12 weeks. Co–primary end points included responder rates assessed by global improvement of irritable bowel syndrome symptoms and the Bristol Stool Scale. Secondary end points included abdominal pain or discomfort, abnormal bowel habit, stool frequency, and Japanese version of IBS-Quality of Life (IBS-QOL-J).

There were no significant differences between groups in baseline characteristics, including mean age (41 years), duration of disease (156 months), and symptoms. The co–primary end point results are shown in Table 1.

Ramosetron rapidly improved symptoms, with significant relief occurring by week 2. Stool consistency improved significantly with ramosetron treatment vs placebo at monthly assessments throughout the trial (P < .001). At the last point, 40.8% of the ramosetron group vs 24.3% of the placebo group showed significant improvement in stool consistency (P < .001). By day 2, patients in the ramosetron group showed an improved Bristol Stool Scale (P = .018 vs placebo). In addition, ramosetron significantly reduced daily stool frequency (P < .001). At study end, ramosetron also significantly improved abdominal pain and discomfort vs placebo (51.4% vs 37.7%; P = .001) and abnormal bowel habits during the study (50.3% vs 31.0%; P < .001). Ramosetron significantly improved some measures of IBS-QOL at study end, including overall quality of life, dysphoria, and food avoidance (P < .01 for all), as well as interference with activity (P < .001).

Ramosetron was associated with significantly more AEs than placebo, including gastrointestinal disorders (P < .001); however, there were no differences between treatment groups in infections and infestations. No ischemic colitis was observed, but the number of patients in the study may be too small to see this AE.

To conclude, ramosetron is effective in women with IBS-D at a dose half of that indicated for men, for reasons that are currently unclear. Improvements in IBS-QOL exceeded the minimal clinically important difference, further supporting ramosetron as therapeutic option for women as well as men.