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

AIM: We assessed the efficacy and safety of 5-hydroxytryptamine (5-HT(3)) 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-HT(3) 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-HT(3) 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-HT(3) receptor antagonists versus placebo was 1.33 (95% CI: 1.26–1.39). The pooled RR showed that 5-HT(3) 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-HT(3) 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-HT(3) receptor antagonists were likelier to cause constipation: the pooled RR of constipation developing with 5-HT(3) 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-HT(3) 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.