Temporal Interference Transcranial Alternating Current Stimulation for Major Depressive Disorder

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) 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. 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 MDD is the change from baseline in the Hamilton Depression Rating Scale (HAMD-17) at week 2. Secondary outcomes include changes in clinical symptoms, cognitive function, and safety profiles.

Inclusion Criteria: 1. Age between 18 and 55 years (inclusive), any gender; 2. Diagnosis of a single or recurrent episode of Major Depressive Disorder (MDD) according to DSM-5 criteria, assessed by trained researchers using the Structured Clinical Interview for DSM-5 (SCID), without psychotic features; 3. HAMD-17 score ≥14; inadequate response despite regular and stable antidepressant treatment at an effective therapeutic dose for at least 6 weeks; 4. Education level: junior high school or above; adequate cognitive and language ability to understand and complete study assessments; 5. Voluntary participation with signed informed consent; ability to comply with study visits, treatment schedules, laboratory tests, and other study procedures. Exclusion Criteria: 1. History of psychiatric disorders other than MDD; 2. Pregnancy or lactation; 3. Neurologic disorders or serious systemic diseases (e.g., thyroid disease, lupus erythematosus, diabetes, hepatic or renal impairment, active infection, major trauma); 4. History of significant head injury or coma 5. Received any standardized neuromodulation therapy targeting the nervous system within the past 6 months before enrollment, including but not limited to electroconvulsive therapy (ECT), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), or vagus nerve stimulation (VNS) 6. Suspected or confirmed history of alcohol or substance dependence; 7. Current severe suicidal ideation or recent suicide attempt; 8. Current participation in another clinical trial or recent use of prohibited psychotropic medications; 9. Positive urine drug screening or abnormal thyroid function tests; 10. Contraindications to magnetic resonance imaging (MRI) or electroencephalography (EEG); 11. Inability to provide fully informed consent.