Efficacy of 5-HT3 Antagonists and 5-HT4 Agonists in Irritable Bowel Syndrome: Systematic Review and Meta-Analysis

OBJECTIVES: Irritable bowel syndrome (IBS) is a chronic functional disorder. 5-Hydroxytryptamine (5-HT) is a key modulator of gastrointestinal sensorimotor function. Many patients have IBS that can be difficult to treat, which has led to the development of newer agents, such as 5-HT(3) antagonists and 5-HT(4) agonists. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the efficacy of all available 5-HT agents in IBS. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to June 2008). Trials recruiting adults with IBS in primary, secondary, or tertiary care comparing 5-HT(3) antagonists or 5-HT(4) agonists with placebo were eligible. Dichotomous symptom data were pooled to obtain a relative risk (RR) of remaining symptomatic after therapy, with a 95% confidence interval (CI). The number needed to treat (NNT) was calculated from the reciprocal of the risk difference. RESULTS: The strategic search identified 1,593 citations. A total of 29 RCTs were eligible for inclusion; placebo was compared with 5-HT(3) antagonists in 11 RCTs, with tegaserod in 11, and with mixed 5-HT(3) antagonists/5-HT(4) agonists in 7. The study quality was generally high. The RR of IBS symptoms persisting with 5-HT(3) antagonists vs. placebo was 0.78 (95% CI: 0.71-0.86), with a similar benefit for both alosetron and cilansetron. Tegaserod was also superior to placebo (RR=0.85; 95% CI: 0.80-0.90). Renzapride and cisapride had no benefit in IBS. CONCLUSIONS: Alosetron, cilansetron, and tegaserod are all effective in the treatment of IBS. Serious adverse events were rare in the eligible RCTs included in this systematic review.