Abstract
AimWe 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).MethodsWe 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.ResultsWe 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]).ConclusionsRamosetron, cilansetron, ondansetron, and alosetron are effective for treating non-constipated IBS and IBS-D. Our systematic review found rare serious adverse events.
Highlights
Irritable bowel syndrome (IBS) is one of the most common functional bowel diseases, and is characterized by abdominal pain and abnormal bowel habits [1]
The pooled relative risk (RR) of global IBS symptoms improved by 5-HT3 receptor antagonists versus placebo or mebeverine was 1.56; 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
Summary
Irritable bowel syndrome (IBS) is one of the most common functional bowel diseases, and is characterized by abdominal pain and abnormal bowel habits [1]. According to the Rome III criteria, IBS is classified into four subtypes: with diarrhea (IBS-D), with constipation (IBS-C), mixed type (IBS-M), and unsubtyped (IBS-U) [2]. The mechanism of its etiology may be related to altered bowel motility and visceral hypersensitivity [3]. Its effect on society is well-recognized because the quality of life of individuals with IBS is profoundly disrupted, and it causes economic loss to such individuals and society due to the medical consultations required and the consumption of other valuable resources. Treatments for IBS are unsatisfactory; only 22% of patients with IBS receiving conventional medical care report at least 50% reduction in bowel symptoms [4]
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