BACKGROUND: Stimulated 5-hydroxytryptamine-3 (5-HT(3)) receptors promote intestinal motility, secretion, and sensation, effects that are related to the known pathophysiology of irritable bowel syndrome (IBS). A previous meta-analysis of 6 randomized controlled trials of the 5-HT(3)-receptor antagonist alosetron found that this agent was associated with global improvement in symptoms, pain, and discomfort in patients with IBS. OBJECTIVE: This was a meta-analysis of randomized, placebo-controlled trials that evaluated the efficacy and tolerability of alosetron for the management of IBS. It updated and expanded on the previous meta-analysis. METHODS: PubMed, EMBASE, SCOPUS, Web of Science, and the cochrane central Register of controlled Trials were searched from 1966 through September 2007 for placebo-controlled trials that examined the efficacy and tolerability of alosetron in the management of IBS. The search terms were alosetron, 5-HT, irritable bowel, functional bowel diseases, and irritable colon. No language restriction was applied. The data were analyzed in terms of 2 main outcomes: global improvement in IBS symptoms and adequate relief of IBS pain and discomfort. RESULTS: Eight multicenter, randomized, placebo-controlled, 12-week clinical trials met the criteria for inclusion in the meta-analysis. The studies included 4,170 patients with IBS (80% female) who were randomized to receive either alosetron or placebo. All patients met the Rome criteria for IBS, and all subtypes of IBS were represented. Most patients had diarrhea-predominant IBS; only 2.6% of patients had constipation-predominant IBS. In the 3 trials included in the analysis of global improvement in symptoms, alosetron was significantly more effective than placebo (relative risk [RR] = 1.60; 95% CI, 1.44-1.76; P <0.001). In the 6 trials included in the analysis of adequate relief of IBS pain and discomfort, there was also a significant difference in favor of alosetron (RR = 1.31; 95% CI, 1.20-1.43; P < 0.001). Analysis of adequate relief of IBS pain and discomfort by sex also indicated significant differences between alosetron and placebo in both sexes (female: RR = 1.34 [95% cI, 1.21-1.48]; male: RR = 1.23 [95% CI, 1.02-1.47]). The analysis of tolerability, which was based on data from 7 studies, found a significant difference between alosetron and placebo (RR = 1.19; 95% cI, 1.07-1.31; P<0.001). The only adverse events that occurred with a significantly higher incidence in those treated with alosetron compared with placebo were constipation in 8 trials (RR = 4.35; 95% CI, 3.01-6.26; P < 0.001) and abdominal pain and discomfort in 5 trials (RR = 1.96; 95% CI, 1.46-2.64; P < 0.001). In the alosetron group, there were 4 cases of ischemic colitis (0.16%) and 2 cases of serious complications of constipation (0.08%); neither of these was reported in the placebo group. Alosetron was not associated with any deaths. CONCLUSIONS: Alosetron was effective in these men and women with IBS. constipation was the most frequently reported adverse event associated with alosetron therapy. Ischemic colitis and serious complications of constipation were reported in a small number of patients treated with alosetron.