5-hydroxytryptamine Receptor Moderator For Irritable Bowel Syndrome: A Systematic Review Of Randomized Controlled Trials

Background: Irritable bowel syndrome (IBS) is a kind of commongastrointestinal disease, which the prevalence is very high and affect patient'squality of life severely. The pathogenesis of irritable bowel syndrome isunclear so that the effective treatments are scare. In spite of many studiesabout 5-hydroxytryptamine receptor moderator in recent ten years, the exacteffeciveness and safety has no distinct conclusion.Objective: This review aims to determine the effectiveness an safety of5-hydroxytryptamine receptor moderator (5-HT3 receptor antagonist and5-HT4 agonist tegoserod) in patients with irritable bowel syndrome.Materials and Methods: Trials were located through electronic searches ofthe Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINEor PUBMED, EMBASE, ISI, OVID Database and WANFANG database. Wealso handsearched the bibliographies of retrieved articles. Two reviewsassessed the quality of studies, extracted data independently. Disagreementswere resolved by discussion or the third party if needed. The primaryoutcomes were assessed: (1) efficacy of global symptom. The second outcomes were: (1) efficacy of individual symptoms (2) advers events (3)quality of life scores.Results: Twenty nine trials involving 16355 patients were included in theMeta-analysis. Quality of the trials is inconsistent. (1) improvement of globalsymptom: alsetron (1 mg bid) was superior to placebo(P＜0.00001); tegaserod(6mg bid, 4 weeks) (P＜0.00001) and tegaserod (6mg bid, 12 weeks)(P＜0.00001) was superior to placebo. (2) efficacy of individual symptoms:1)efficacy of pain: alosetron (1 mg bid) was superior to placebo(P＜0.00001);tegaserod (6mg bid,4 weeks) (P＜0.00001) and tegaserod (6mg bid, 12 weeks)(P=0.044) was suprerior to placebo; tegoserod was suprerior to cisapride(P=0.03). 2) efficacy of bowel urgency: alsetron (1mg bid) was superiorto placebo (P=0.0001). 3) efficacy of constipation: tegaserod (6mg bid)was superior to placebo (P=0.0009). 4) efficacy of abdominal distension:tegaserod (6mg bid) was superior to placebo (P＜0.0001) and cisapride (P=0.03). (3) adverse events: alosetron (1mg bid) was higher than placebo(P=0.006); tegaserod (6mg bid) (P=0.0008) and tegaserod (2mg bid)(P=0.03) was higher than placebo. 1) constipation: alosetron (1mg bid) washigher than placebo (P＜0.00001). 2) ischemic colitis: only one ischemiccolitis in all including studies. 3) diarrhea: tegaserod was higher than placebo(P=0.0002). 4) headache: tegaserod was higher than placebo (P=0.02). (4)improvement of life quality: alosetron (1mg bid) was superior to placebo inIBSQOL questionnaire (P＜0.05), tegaserod(6mg bid)was superior to placeboin work productivity and activities impairment (P＜0.0001).Conclusions: The limited current evidence showed that: alosetron andtegaserod were superior to placebo in improvement of the global symptoms. Alosetron was superior to placebo in improvement of pain and bowel urgency.Tegaserod was superior to placebo in improvement of pain, constipation andabdominal distention and superior to cisapride in that of pain and abdominaldistention. Both alosetron and tegaserod can improvement life quality ofpatients with IBS. However, the adverse events of alosetron and tegaserodwere much more than placebo. Because of limited studies and poor quality ofsome studies, the above conclusions were needed to be cautious to beapplicated.