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

Abstract

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.

• Authors: Alexander C Ford, Lawrence J Brandt, Christine Young, William D Chey, Amy E Foxx-Orenstein, Paul Moayyedi
• Journal: The American journal of gastroenterology (Am J Gastroenterol) Vol. 104 Issue 7 Pg. 1831-43; quiz 1844 (Jul 2009) ISSN: 1572-0241 [Electronic] United States
• PMID: 19471254 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

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

Topics

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