• Shaoyuan Li, Peijing Rong, Yu Wang, Guixing Jin, Xiaobing Hou, Suxia Li, Xue Xiao, Wei Zhou, Yue Wu, Yaping Liu, Yue Zhang, Bin Zhao, Yiting Huang, Jin Cao, Helen Chen, Sierra Hodges, Mark Vangel, and Jian Kong.
• Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China.
• Neuromodulation. 2022 Apr 1; 25 (3): 450-460.

ObjectivesMajor depressive disorder (MDD) is one of the most common mental illnesses. This study aims to investigate the effectiveness of transcutaneous auricular vagus nerve stimulation (taVNS) compared with the effectiveness of citalopram, a commonly used antidepressant, in patients with depression.Material And MethodsA total of 107 male and female patients with MDD (55 in the taVNS group and 52 in the citalopram group) were enrolled in a prospective 12-week, single-blind, comparative effectiveness trial. Participants were recruited from the outpatient departments of three hospitals in China. Participants were randomly assigned to either taVNS treatment (eight weeks, twice per day, with an additional four-week follow-up) or citalopram treatment (12 weeks, 40 mg/d). The primary outcome was the 17-item Hamilton Depression Rating Scale (HAM-D17) measured every two weeks by trained interviewers blinded to the treatment assignment. The secondary end points included the 14-item Hamilton Anxiety Scale and peripheral blood biochemical indexes.ResultsThe HAM-D17 scores were reduced in both treatment groups; however, there was no significant group-by-time interaction (95% CI: -0.07 to 0.15, p = 0.79). Nevertheless, we found that taVNS produced a significantly higher remission rate at week four and week six than citalopram. Both treatments were associated with significant changes in the peripheral blood levels of 5-hydroxytryptamine, dopamine, γ-aminobutyric acid, and noradrenaline, but there was no significant difference between the two groups.ConclusiontaVNS resulted in symptom improvement similar to that of citalopram; thus, taVNS should be considered as a therapeutic option in the multidisciplinary management of MDD. Nevertheless, owing to the design of this study, it cannot be ruled out that the reduction in depression severity in both treatment groups could be a placebo effect.Copyright © 2021. Published by Elsevier Inc.

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