Efficacy and safety of 5-hydroxytryptamine 3 receptor antagonists in irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.

Abstract

AIM:

We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT3) receptor antagonists in adults with non-constipated irritable bowel syndrome (IBS) or diarrhea-predominant IBS (IBS-D).

METHODS:

We searched PubMed, MEDLINE, EMBASE, and the Cochrane Controlled Trials Register for randomized controlled trials (RCTs) involving adults with non-constipated IBS or IBS-D that compared 5-HT3 receptor antagonists with placebo or other conventional treatment. Dichotomous symptom data were pooled to obtain the relative risk (RR) and 95% confidence intervals (CIs) for improving global IBS symptoms, abdominal pain and abnormal bowel habits, or stool consistency symptoms after therapy, and adverse events, including constipation. Meta- analysis was performed with Mantel Haenszel method using Revman 5.3 software.

RESULTS:

We included 21 RCTs; 16 were high quality (Jadad score ≥ 4). The pooled RR of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56 (95% CI: 1.43-1.71); alosetron, ramosetron, and cilansetron had similar treatment effects. The pooled RR of abdominal pain relieved by 5-HT3 receptor antagonists versus placebo was 1.33 (95% CI: 1.26-1.39). The pooled RR showed that 5-HT3 receptor antagonists improved abnormal bowel habits or stool consistency symptoms (RR = 1.63, 95% CI: 1.33, 1.99). The pooled RR of adverse events following 5-HT3 receptor antagonist treatment was 1.15 (95% CI: 1.08, 1.22). Subgroup analysis indicated that alosetron had a high rate of adverse effects (RR = 1.16, 95% CI: 1.08, 1.25); adverse events following ramosetron treatment were not statistically significantly different. 5-HT3 receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT3 receptor antagonist versus placebo was 3.71 (95% CI: 2.98-4.61). However, constipation was likelier in patients with non-constipated IBS after taking 5-HT3 receptor antagonists than in patients with IBS-D only (non-constipated IBS and IBS-D: RR = 5.28 [95% CI: 3.93, 7.08] vs. IBS-D only 3.24 [2.54, 4.12]).

CONCLUSIONS:

Ramosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.

• Authors: Yongping Zheng, Ting Yu, Yurong Tang, Wenjie Xiong, Xiaoxue Shen, Ling Jiang, Lin Lin
• Journal: PloS one (PLoS One) Vol. 12 Issue 3 Pg. e0172846 ( 2017) ISSN: 1932-6203 [Electronic] United States
• PMID: 28291778 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Placebos
• Serotonin 5-HT3 Receptor Antagonists

Topics

• Humans
• Irritable Bowel Syndrome (drug therapy)
• Placebos
• Serotonin 5-HT3 Receptor Antagonists (therapeutic use)