Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis

Am J Gastroenterol. 2009 Jul;104(7):1831-43; quiz 1844. doi: 10.1038/ajg.2009.223. Epub 2009 May 26.


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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Carbazoles / administration & dosage
  • Carbazoles / adverse effects
  • Carbolines / administration & dosage
  • Carbolines / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Education, Medical, Continuing
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Irritable Bowel Syndrome / diagnosis*
  • Irritable Bowel Syndrome / drug therapy*
  • Male
  • Middle Aged
  • Patient Satisfaction
  • Pyridines / administration & dosage
  • Pyridines / adverse effects
  • Quality of Life*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Serotonin Antagonists / administration & dosage*
  • Serotonin Antagonists / adverse effects
  • Severity of Illness Index
  • Sex Factors
  • Treatment Outcome


  • Carbazoles
  • Carbolines
  • Indoles
  • Pyridines
  • Serotonin Antagonists
  • alosetron
  • cilansetron
  • tegaserod