A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea-predominant irritable bowel syndrome

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen in primary care practice. The symptoms of IBS, including abdominal pain, discomfort, and abnormal bowel function, may be modulated by activity of the serotonin type 3 receptor (5-HT3). The efficacy and tolerability of the 5-HT3 receptor antagonist alosetron hydrochloride in nonconstipated female patients with IBS were evaluated in a double-blind, randomized, placebo-controlled trial. Methods: Patients received either 1 mg of alosetron hydrochloride (n=309) or placebo (n=317) twice daily for 12 weeks, followed by a 4-week post-treatment period. Adequate relief of IBS pain and discomfort was the primary end point. Secondary end points included improvements in urgency, stool frequency, stool consistency, incomplete evacuation, and bloating. Results: Seventy-one percent of patients were classified as having diarrhea-predominant IBS. Forty-three percent of alosetron-treated patients with diarrhea-predominant IBS. reported adequate relief for all 3 months compared with 26% of placebo-treated patients (P<.001; percentage point difference= 17; 95% confidence interval, 8.0-25.4). Improvement with alosetron compared with placebo was observed by the end of the fourth week of treatment and persisted throughout the remainder of treatment. Alosetron significantly decreased urgency and stool frequency and caused firmer stools within 1 week of starting treatment. Effects were sustained throughout treatment and symptoms returned following treatment cessation. No significant improvement in the percentage of days with sense of incomplete evacuation or bloating was observed compared with placebo during the first month of treatment. Constipation was the most commonly reported adverse event. Conclusion: Alosetron hydrochloride, 1 mg twice daily for 12 weeks, is effective in relieving pain and some bowel-related symptoms in diarrhea-predominant female patients with IBS.