Effect of transcutaneous vagus nerve stimulation with electrical stimulation on generalized anxiety disorder: Study...

Generalized anxiety disorder (GAD) is the most common type of anxiety disorder and can cause severe damage to patients and increase medical and social burdens. Vagus nerve stimulation (VNS) has been used for treating mental disorders, but the involvement of surgery, perioperative risks, and potentially significant side effects have limited this treatment. Anatomical studies have shown that the ear is the only area where the afferent vagus nerve is distributed on the skin. Recently, the safety and efficacy of transcutaneous auricular vagus nerve stimulation (t-VNS) with electrical stimulation for depression and epilepsy have been objectively evaluated. This trial is trying to evaluate the efficacy of t-VNS with electrical stimulation for the treatment of GAD and explore the potential underlying neural mechanism using fMRI.

An assessor-participant blinded, randomized sham-controlled trial will be performed. Sixty participants with GAD will be randomly assigned to the t-VNS group or sham t-VNS group. The treatment will last for 8 weeks, once every 30 min and twice a day. Four clinical assessments will be conducted: before treatment, at 2 weeks, at 4 weeks, and posttreatment. The primary outcome parameter is the categorical classification of treatment response in the Hamilton Anxiety Rating Scale (HAMA) score. Functional magnetic resonance imaging (fMRI) scans will be applied, and the alterations in Amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) on resting-state fMRI will be compared between the two groups before and after treatment. Moreover, the correlation between the changes in clinical symptoms and the changes in the altered ALFF and FC in the two groups will be analyzed.

This high-level evidence-based medical research is expected to evaluate the value of t-VNS in treating GAD and provide a preliminary explanation of its mechanism of action in brain functional imaging. In addition, the use of t-VNS devices has substantially decreased time and financial costs, potentially providing a promising option for complementary alternative medicine in the treatment of GAD, thereby advancing treatment decisions for this condition.

International Traditional Medicine Clinical Trial Registry, ITMCTR2022000099. Registered on June 30, 2022.