Efficacy of 5-HT3 antagonists and 5-HT4 agonists in irritable bowel syndrome: systematic review and meta-analysis.
OBJECTIVE
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.
Ford
Alexander C
AC
Gastroenterology Division, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada. alexf12399@yahoo.com
Brandt
Lawrence J
LJ
Young
Christine
C
Chey
William D
WD
Foxx-Orenstein
Amy E
AE
Moayyedi
Paul
P
D000328:Adult; D000367:Age Factors; D000368:Aged; D002227:Carbazoles / Q000008:administration & dosage / Q000009:adverse effects; D002243:Carbolines / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004502:Education, Medical, Continuing; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D043183:Irritable Bowel Syndrome / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D017060:Patient Satisfaction; 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; D012737:Sex Factors; D016896:Treatment Outcome
D002227:Carbazoles; D002243:Carbolines; D007211:Indoles; D011725:Pyridines; D012702:Serotonin Antagonists; C090840:alosetron; C084473:cilansetron; C105050:tegaserod