| Background:Irritable bowel syndrome(IBS)is a common functional gastrointestinal disorder.The latest Roman Ⅳ classifies IBS as irritable bowel syndrome with diarrhea(IBS-D)and irritable bowel syndrome with constipation(IBS-D).Irritable bowel syndrome with mixed bowel habits(IBS-M),and irritable bowel syndrome with unclassified(IBS-U).The prevalence of IBS in the Chinese population is about 1.4%to 11.5%,of which IBS-D is the most common subtype.Diarrhea symptoms seriously affect the work,study and life quality of patients,and increase the economic burden.Because the pathogenesis of IBS-D is still unclear,there are many therapeutic drugs for IBS-D at present,but the efficacy evaluation is different.Objective:This study was divided into two parts.In the first part,the efficacy and safety of single drug of clinically common drugs(antidiarrhaetics,spasmolytics,probiotics,antidepressants,5-HT3 receptor antagonists,opioid receptor agonists,aminosalicylic acid)compared with placebo in the treatment of BS-D were analyzed by Meta.In the second part,the efficacy and safety of one antidepressant combined with one commonly used drug compared with one commonly used drug alone in the treatment of IBS-D were analyzed by Meta-analysis..Methods:Literature databases including CNKI,PubMed,WanFang,The Cochrane Library,EMbase and CBM were searched for "irritable bowel syndrome","diarrhea","randomized controlled trial" and subject words and free words of The above seven drugs.All literatures related to randomized controlled trial were searched from The database establishment to December 2020.The Cochrane risk assessment tool was used to evaluate the quality of the included literature.Q test and I2 in Review Manager(Rev Man)5.3 software were used to test the heterogeneity of the included study data.If the heterogeneity was high,sensitivity analysis was conducted to exclude relevant data,and then heterogeneity test was conducted until the homogeneity was met between the data.The fixed effect model was used to analyze the overall symptom improvement rate and the incidence of adverse reactions of different kinds of drugs in the included literature.Relative risk(RR)and 95%confidence interval(CI)were calculated.The publication bias was tested by drawing funnel plot.Results:In the first part,20 randomized controlled trials involving 19,390 patients with single-agent versus placebo treatment for IBS-D were included,including 7 classes of antidiarrhetics,spasmolytics,probiotics,antidepressants,5-HT3 receptor antagonists,opioid receptor agonists,and aminosalicylic acid.The results showed that antidepressants[RR=1.73,95%CI(1.32,2.25),P<0.0001],spasmolysis medicine[RR=1.72,95%CI(1.41,2.10),P<0.00001],probiotics(RR=1.57,95%CI(1.22,2.03),P<0.0001],opioid agonist[RR=1.63,95%CI(1.45,1.83),P<0.0001]The overall symptom improvement rate was significantly higher in patients treated with IBS-D than with placebo.Antidiarrhoea[RR=1.20,95%CI(1.01,1.44),P=0.04]had a smaller improvement rate in overall symptoms than placebo.Aminosalicylic acid RR=1.11,95%CI(0.79,1.56),P=0.56]showed no significant difference in the overall symptom improvement rate between patients and placebo.5-Th3 receptor antagonist in female IBS-D patients[RR=1.52,95%CI(1.45,1.59),P<0.00001];Women treated with alosetron 0.5mg qd or 1mg qd or 1mg bid had significantly higher overall symptom improvement rates than placebo.However,ramosetron either 1,5 or 10ug qd was only marginally more effective than placebo at 4 weeks[RR=1.55,95%CI(1.08,2.22),P=0.02],and continued treatment was comparable to placebo.The overall symptom improvement rate of ramosetron in IBS-D male patients was significantly higher than that of placebo[RR=2.10,95%CI(1.86,2.38),P<0.00001].In this study,adverse reaction effect size of patients with IB S-D treated with 5-Th3 receptor antagonist was found[RR=1.26,95%CI(1.17,1.36),P<0.0001]was slightly higher than placebo,and the adverse reactions of other drugs were similar to placebo.Patients with IBS-D were better treated with low-dose antidepressants,and no significant increase in side effects was observed.However,due to the limited number of controlled trials involving antidepressants versus placebo in the treatment of IBS-D,the second part of the study failed to cover the types of antidepressants commonly used in clinical practice.In the second part,a total of 28 randomized controlled trials involving 2748 patients were included in which an antidepressant was combined with a commonly used drug to treat IBS-D alone.Among them,there were 1029 cases of TCAS in the experimental group and 949 cases in the control group.SSRI combined treatment group 105 cases,control group 100 cases;There were 223 cases in the SNRI combined treatment group and 213 cases in the control group.There were 53 patients in the NASSA combined treatment group and 53 patients in the control group.The overall symptom improvement rate of IBS-D patients treated with antidepressants combined with common drugs was higher than that treated with common drugs alone,RRTCAS=1.28,95%CI(1.23,1.34),P<0.00001;Other antidepressants RR=1.33,95%CI(1.23,1.44),P<0.00001.The adverse reactions described in the included literatures were mainly TCAs,the incidence effect size of adverse reactions RR=2.54,95%CI(1.31,4.93),P=0.006.However,no obvious adverse reactions were found in the original literature of the combination of SNRI and NASSA drugs,which were not included in the statistics.Conclusion:Monotherapy with antidepressants,opioid receptor agonists and 5-Th3 receptor antagonists can significantly improve the overall symptom improvement rate of IBS-D patients,and low-dose antidepressant monotherapy has obvious ad vantages.The efficacy of spasmolytic drugs and probiotics alone in the treatment of IBS-D was similar,but not much superior to placebo.Patients with IBS-D treated with antidiarrhoea and aminosalicylic acid monotherapy showed poor overall symptom improvement.Adverse reactions were slightly higher in patients with IBS-D treated with 5-Th3 receptor antagonist monotherapy than placebo,and alosetron was used only in women.There was no significant difference in the safety of other monotherapy types of IBS-D compared with placebo.The efficacy of TCAS or SSRI or SNRI or NASSA antidepressants and commonly used drugs in IBS-D treatment was significantly higher than that of commonly used drugs alone.The incidence of adverse reactions was slightly increased after TCAS and SSRI combined treatment.In general,antidepressant combination treatment of IBS-D can significantly improve patients’ satisfaction with treatment,and no serious adverse reactions were reported.Due to the small number of included literatures,the efficacy and safety of combined use of SSRI or SNRI or NASSA,and the stability of results need to be further studied. |
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