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.
OBJECTIVE
We performed a systematic review and meta-analyses to estimate treatment efficacy and constipation rate of 5-hydroxytryptamine (serotonin) (5-HT(3)) 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-HT(3) 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-HT(3) 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; I(2) = 0%) and relief of abdominal pain and discomfort (pooled relative risk, 1.30; 95% CI, 1.22-1.39; I(2) = 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, I(2) = 65%); there was less constipation with 5-HT(3) 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-HT(3) antagonists had possible ischemic colitis versus none in control groups.


CONCLUSIONS
5-HT(3) antagonists significantly improve symptoms of NC-IBS or D-IBS in men and women. There is an increased risk of constipation with 5-HT(3) antagonists, although the risk is lower in those with D-IBS.
Andresen
Viola
V
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Montori
Victor M
VM
Keller
Jutta
J
West
Colin P
CP
Layer
Peter
P
Camilleri
Michael
M
D000284:Administration, Oral; D002227:Carbazoles / Q000008:administration & dosage* / Q000009:adverse effects; D002243:Carbolines / Q000008:administration & dosage* / Q000009:adverse effects; D003248:Constipation / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D003967:Diarrhea / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010627:Phenethylamines / Q000008:administration & dosage* / Q000009:adverse effects; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002227:Carbazoles; D002243:Carbolines; D010627:Phenethylamines; D011725:Pyridines; D012702:Serotonin Antagonists; C090840:alosetron; C084473:cilansetron; C005096:mebeverine