Effects of Jie Yu Wan on Generalized Anxiety Disorder: A Randomized Clinical Trial

OBJECTIVE: To systematically assess the clinical efficacy of the Jie Yu Wan (JYW) formula in treating generalized anxiety disorder (GAD). METHODS: A multicenter, prospective, double-blind, double-dummy, randomized controlled trial (RCT) was conducted at four hospitals in China. A total of one hundred thirty-three patients with GAD were enrolled from 2017 to 2019. This study aimed to evaluate the effects of a Traditional Chinese Medicine (TCM) JYW formula on GAD at eight weeks, with the use of Buspirone as the comparator. A stepwise dosing protocol was used (JYW: high dose 24 g/day, low dose 12 g/day; Buspirone: high dose 30 mg/day, low dose 15 mg/day) and the dose was adjusted depending on whether the treatment response of Hamilton Anxiety Scale (HAMA) score was less than or equal to 25% after one week. The primary outcome was a change in total score on the HAMA. The secondary outcomes included the Hamilton Depression Scale (HAMD), Clinical Global Impression (CGI) scale, and TCM Syndrome Scale. Adverse events were recorded using the Treatment Emergent Symptom Scale (TESS). Assessments were conducted at the baseline and 1, 2, 4, and 8 weeks. RESULTS: A total of one hundred thirty-three participants were randomly assigned to the JYW group (n = 66) and the Buspirone group (n = 67). One hundred twenty-one patients (91%) completed at least one follow-up session. There were no significant differences between the two groups in terms of gender, age, disease course, HAMA, HAMD, CGI, and TCM Syndrome Scale scores at baseline (all P > 0.05). Repeated-measures analysis of variance revealed statistically significant time effects for the HAMA (P=0.002), HAMD (P = 0.018), and CGI (P=0.001) in both groups. Sensitivity analyses supported the credibility of the main results (P > 0.05). The group effect was not significant for the HAMA (P=0.43), HAMD (P=0.27), CGI (P=0.37), and TCM Syndrome Scale (P=0.86). Furthermore, there were no significant interaction effects between time and group in terms of the HAMA (P=0.47), HAMD (P=0.79), CGI (P=0.67), and TCM Syndrome Scale (P=0.69). After one week, 53 patients (80%) of the JYW group and 52 patients (78%) of the Buspirone group were adjusted to high doses. The interaction effect between time, group, and the dose was determined by repeated measures ANOVA test, and the HAMA score served as the outcome measure. The interaction effect between time and dose was statistically significant (P=0.04), which shows that high-dose JYW (24 g/day) was more effective in decreasing patients' HAMA scores than low-dose JYW (12 g/day), and Buspirone had the same effect, which means that high-dose Buspirone (30 mg/day) was more effective than low dose. (15 mg/day). CONCLUSIONS: The conclusion of this study supports that JYW and Buspirone can effectively alleviate the anxiety symptoms of GAD patients, which are both effective and safe for treatment of mild to moderate GAD. Besides, high-dose JYW or Buspirone are more effective than low-dose, which is of great importance in assisting clinical medication choice.