Review Efficacy and safety of Xiaoyao San in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis 2025 Wang et al

[Andy]

Background: Xiaoyao San (XYS) has been increasingly used in China for treating chronic fatigue syndrome (CFS), but its efficacy and safety remain unclear.

Objective: To systematically evaluate the efficacy and safety of XYS compared to standard biomedical treatments (SBT) in CFS patients.

Methods: A comprehensive search of English and Chinese databases was conducted up to December 2024. Eligible studies included randomized controlled trials comparing XYS or XYS + SBT to SBT alone. Primary outcomes were effective rate (ER) and fatigue scale-14 (FS-14). Secondary outcomes included self-rating anxiety scale (SAS), self-rating depression scale (SDS), and adverse events (AEs). Data were analyzed using Review Manager 5.4, and evidence quality was assessed using the GRADE approach.

Results: Six studies involving 623 patients were included. The meta-analysis showed that XYS-based interventions significantly improved ER (RR = 1.27, 95% CI: 1.18–1.37, I2 = 0%) and FS-14 (MD = 1.77, 95% CI: 1.49–2.06, I2 = 54%). Subgroup analyses confirmed consistent efficacy for both XYS vs. SBT and XYS + SBT vs. SBT. Anxiety and depression improved significantly in the XYS + SBT group, with SAS (MD = 5.16, 95% CI: 3.84–6.48, I2 = 24%) and SDS (MD = 4.62, 95% CI: 3.15–6.09, I2 = 0%). Additionally, the risk of AEs was significantly reduced in the XYS + SBT group compared to SBT alone (RR = 0.48, 95% CI: 0.32–0.72, I2 = 0%). However, the quality of evidence was rated “low” due to risk of bias and potential publication bias among the studies.

Conclusion: XYS, whether alone or with SBT, is effective and safe for improving ER, fatigue, anxiety, and depression in CFS patients. However, due to the low quality of the evidence, results should be interpreted cautiously. High-quality RCTs with larger sample sizes and longer follow-up are needed to provide stronger evidence for the clinical use of XYS in managing CFS.

Open access

 

[Utsikt]

XYS, whether alone or with SBT, is effective and safe for improving ER, fatigue, anxiety, and depression in CFS patients. However, due to the low quality of the evidence, results should be interpreted cautiously.

They should take their own advice for the first sentence.

 

[rvallee]

Xiaoyao San (XYS) has been increasingly used in China for treating chronic fatigue syndrome (CFS), but its efficacy and safety remain unclear

Ah, good old evidence-based medicine, where a completely ridiculous statement like this is not only normal, but almost a universal standard. It's really amazing how health care is the only industry where something like this can occur. Because in all other industries everyone would look at a proposal to use something without any evidence with a concerned "uh, are you OK? do you need an extended vacation?" look and prompt dismissal.

But here? Perfectly normal. And not because it's TCM, actually they are borrowing from the EBM playbook and applying it exactly as it is commonly practiced. In fact this would likely get a moderate rating from applying GRADE, depending on what the people doing the grading think of TCM. Because in the end it's literally the only thing that matters: what people think of the treatment and its rationale. Evidence is entirely irrelevant to the process, it goes whichever way the cultural beliefs go.

 

[forestglip]

Commentary: Efficacy and safety of Xiaoyao San in the treatment of chronic fatigue syndrome: a systematic review and meta-analysis

Runhua Zhang, Hongxia Hu

We read with great interest the recent systematic review and meta-analysis evaluating the efficacy and safety of XYS for the treatment of CFS. This study provides timely and valuable insights, particularly in the context of the post-COVID era where CFS-like symptoms have received renewed attention. Synthesizing data from six randomized controlled trials (RCTs), the authors report that XYS significantly improves clinical symptoms such as fatigue, anxiety, and depression with few adverse events (1). While the findings are encouraging, several methodological and clinical issues require deeper reflection to assess the reliability, applicability, and future direction of this research.

First, we note significant limitations in the quality and standardization of the included RCTs. [...]

Second, we are concerned about the substantial clinical and pharmacological heterogeneity introduced by the use of “Modified XYS” across the included trials. [...]

Third, the use of "effective rate" (ER) as the primary outcome deserves critical scrutiny. [...]

Finally, while the review briefly outlines several possible mechanisms—such as modulation of mitochondrial energy metabolism, Th1/Th2 and Th17/Treg immune balance, HPA axis regulation, and gut microbiota composition—these remain largely speculative. [...]

Web | Frontiers in Pharmacology | Provisionally accepted

 

[Utsikt]

Moreover, ER does not capture the severity, persistence, or multidimensional nature of fatigue, which is central to the clinical burden of CFS. In contrast, validated instruments such as the Chalder Fatigue Scale quantify fatigue across both physical and mental domains (3), while the SF-36 includes subscales for vitality, role functioning, and general health perceptions (4). These tools enable a more nuanced, reproducible, and internationally comparable assessment of therapeutic outcomes. Future trials should prioritise such validated scales to enhance both the internal validity and global relevance of outcome measurement in CFS research.

I’m sure using the CFS and SF-36 is going to be so much better..