This multi-center, double-blind study, randomized controlled trial aims to evaluate the efficacy and safety of Temporal Interference transcranial Alternating Current Stimulation (TI-tACS) in patients with major depressive disorder (MDD) and generalized anxiety disorder (GAD).
All participants will be enrolled as two independent cohorts and randomized separately within each diagnostic group. Participants with major depressive disorder will be randomized to receive high-frequency TI-tACS(130 Hz), low-frequency TI-tACS(2Hz), or sham stimulation targeting the right amygdala. Participants with generalized anxiety disorder will be randomized to receive high-frequency TI-tACS(80Hz), low-frequency TI-tACS(5Hz), or sham stimulation targeting the right amygdala.
The intervention consists of 20 stimulation sessions administered over 2 weeks (twice a day for 5 consecutive days, followed by a 2-day break, and another 5 consecutive days). Clinical assessments will be conducted at baseline, during treatment, and at multiple follow-up time points up to 6 months.
The primary outcome for the MDD cohort is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. The primary outcome for the GAD cohort is the change from baseline in the Hamilton Anxiety Rating Scale (HAMA) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles in both the MDD and GAD cohorts.
Age between 18 and 55 years (inclusive), any gender;
Diagnosis of a single or recurrent episode of Major Depressive Disorder (MDD) or Generalized Anxiety Disorder (GAD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features;
For MDD participants: HAMD-17 score ≥14; inadequate response to stable, regular antidepressant medication for at least 1 month at an adequate dose;
For GAD participants: HAMA score ≥14; stable, regular medication for at least 2 months;
History of psychiatric disorders other than MDD or GAD;
Pregnancy or lactation;
Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma);
History of significant head injury or coma
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Treatment groupsSee each treatment group below.
Central South University
Lead sponsor
Second Xiangya Hospital of Central South University
Collaborator
Lanzhou University Second Hospital
Collaborator
Neuropsychiatric Institute of Fuzhou Second General Hospital
Collaborator
Affiliated Wuhan Mental Health Center of Huazhong University of Science and Technology
Collaborator
Affiliated WuTaiShan Hospital of Medical College of Yangzhou University
Collaborator
Xianyue Psychiatric Hospital, Xiamen
Collaborator