Efficacy and Safety of Chinese Herbal Medicine Xiao Yao San in Functional Gastrointestinal Disorders: A meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Background and Aims: Functional gastrointestinal disorders are now named disorders of gut-brain interaction (DGBI) according to the Rome IV criteria, characterized by the interaction of gastrointestinal symptoms and dysregulation of central nervous systems. Xiao-Yao-San (XYS) is effective in the treatment of gastrointestinal symptoms in China, especially in patients with concurrent mood disorders. A meta-analysis was designed to evaluate the efficacy and safety of Xiao-Yao-San for FGIDs.Methods: We searched randomized controlled trials in seven databases from their inception till November 22, 2021. Pooled analysis included therapeutic efficacy, symptom score, Self-Rating Anxiety Scale (SAS) score, Self-Rating Depression Scale (SDS) score, and the recurrence rate. Conventional meta-analysis with random-effects model or fixed-effects model and trial sequential analysis (TSA) were performed.Results: A total of 48 RCTs were eligible for inclusion (n = 4,403). Meta-analysis results showed that XYS could improve the effective rate of FGIDs compared with western drugs [RR = 1.23; (95%CI, 1.19-1.27); p < 0.00001], and XYS combined with western medicine could also improve the effective rate [RR = 1.26; (95%CI, 1.21-1.33); p < 0.00001]. In addition, XYS could reduce the symptom score [SMD = -1.07; (95%CI -1.42, -0.72); Z = 6.03; p < 0.00001], SAS score [MD = -6.24; (95%CI -7.48, -4.99); Z = 9.81; p < 0.00001] and SDS score [MD = -6.70; (95%CI -8.18, -5.21); Z = 8.83; p < 0.00001] of FGIDs patients, and reduce the recurrence rate [MD = -6.70; (95%CI -8.18, -5.21); Z = 8.83; p < 0.00001]. XYS was safe in most cases and no serious adverse events were observed in any of the included trials. TAS showed adequate "information size " for the primary outcome, and further confirmed the efficacy of XYS in the treatment of FGIDs.Conclusion: XYS could improve symptoms and reduce recurrence rates in FGIDs patients, and XYS may be a potential candidate for the treatment of FGIDs. However, due to the limited quality of current studies, more long-term, randomized, double-blinded clinical trials are needed in future studies.