Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome

A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Viola Andresen, Victor Manuel Montori, Jutta Keller, Colin Patrick West, Peter Layer, Michael Camilleri

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Background & Aims: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT3) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). Methods: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT3 antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. Results: We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT3 antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval [CI], 1.49-1.72; I2 = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I2 = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I2 = 65%); there was less constipation with 5-HT3 antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT3 antagonists had possible ischemic colitis versus none in control groups. Conclusions: 5-HT3 antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT3 antagonists, although the risk is lower in those with D-IBS.

Original languageEnglish (US)
Pages (from-to)545-555
Number of pages11
JournalClinical Gastroenterology and Hepatology
Volume6
Issue number5
DOIs
StatePublished - May 2008

Fingerprint

Irritable Bowel Syndrome
Constipation
Serotonin 5-HT3 Receptor Antagonists
Meta-Analysis
Serotonin
Randomized Controlled Trials
Confidence Intervals
Ischemic Colitis
Proxy
MEDLINE
Abdominal Pain
Population
Diarrhea
Odds Ratio
Placebos
Safety
Control Groups

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{b4a90a9143644ac88427acdb3691628d,
title = "Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials",
abstract = "Background & Aims: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT3) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). Methods: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT3 antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. Results: We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT3 antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95{\%} confidence interval [CI], 1.49-1.72; I2 = 0{\%}) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95{\%} CI, 1.22-1.39; I2 = 22{\%}). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95{\%} CI, 3.28-5.60, I2 = 65{\%}); there was less constipation with 5-HT3 antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95{\%} CI, 0.41-0.99). Nine patients (0.2{\%}) using 5-HT3 antagonists had possible ischemic colitis versus none in control groups. Conclusions: 5-HT3 antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT3 antagonists, although the risk is lower in those with D-IBS.",
author = "Viola Andresen and Montori, {Victor Manuel} and Jutta Keller and West, {Colin Patrick} and Peter Layer and Michael Camilleri",
year = "2008",
month = "5",
doi = "10.1016/j.cgh.2007.12.015",
language = "English (US)",
volume = "6",
pages = "545--555",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",
number = "5",

}

TY - JOUR

T1 - Effects of 5-Hydroxytryptamine (Serotonin) Type 3 Antagonists on Symptom Relief and Constipation in Nonconstipated Irritable Bowel Syndrome

T2 - A Systematic Review and Meta-Analysis of Randomized Controlled Trials

AU - Andresen, Viola

AU - Montori, Victor Manuel

AU - Keller, Jutta

AU - West, Colin Patrick

AU - Layer, Peter

AU - Camilleri, Michael

PY - 2008/5

Y1 - 2008/5

N2 - Background & Aims: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT3) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). Methods: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT3 antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. Results: We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT3 antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval [CI], 1.49-1.72; I2 = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I2 = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I2 = 65%); there was less constipation with 5-HT3 antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT3 antagonists had possible ischemic colitis versus none in control groups. Conclusions: 5-HT3 antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT3 antagonists, although the risk is lower in those with D-IBS.

AB - Background & Aims: We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT3) antagonists in patients with nonconstipated (NC) or diarrhea-predominant (D)-irritable bowel syndrome (IBS). Methods: Two reviewers independently searched MEDLINE, EMBASE, and Web of Science (January 1, 1966 to December 15, 2006) for randomized controlled trials of 5-HT3 antagonists in IBS reporting clinical end points of the IBS symptom complex and safety parameters. Study characteristics, markers of methodologic quality, and outcomes for the intention-to-treat population for each randomized controlled trial were extracted independently. Results: We found 14 eligible randomized controlled trials of alosetron (n = 3024) or cilansetron (n = 1116) versus placebo (n = 3043) or mebeverine (n = 304). Random-effects meta-analyses found 5-HT3 antagonists more effective than the comparators in achieving global improvement in IBS symptoms (pooled relative risk, 1.60; 95% confidence interval [CI], 1.49-1.72; I2 = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I2 = 22%). Benefit was apparent for both agents, in patients of either sex. These agents were more likely to cause constipation (pooled relative risk, 4.28; 95% CI, 3.28-5.60, I2 = 65%); there was less constipation with 5-HT3 antagonists in D-IBS patients than in mixed populations (NC-IBS and D-IBS; relative risk ratio, 0.65; 95% CI, 0.41-0.99). Nine patients (0.2%) using 5-HT3 antagonists had possible ischemic colitis versus none in control groups. Conclusions: 5-HT3 antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT3 antagonists, although the risk is lower in those with D-IBS.

UR - http://www.scopus.com/inward/record.url?scp=42749097353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42749097353&partnerID=8YFLogxK

U2 - 10.1016/j.cgh.2007.12.015

DO - 10.1016/j.cgh.2007.12.015

M3 - Article

VL - 6

SP - 545

EP - 555

JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

IS - 5

ER -