Overview
This randomized, double-blind, sham-controlled pilot study will evaluate the feasibility, acceptability, safety, and preliminary clinical effects of transcranial alternating current stimulation as an adjunctive treatment for adolescents with major depressive disorder. It will also examine changes in depressive symptoms and related clinical outcomes, while exploring potential effects on emotional regulation, cognitive function, and brain function following the intervention.
Description
This randomized, double-blind, sham-controlled pilot trial will evaluate transcranial alternating current stimulation (tACS) as an adjunct to stable pharmacotherapy in adolescents with major depressive disorder (MDD). Eligible participants will be aged 12-18 years, meet DSM-5 criteria for a current depressive episode, have a Children's Depression Rating Scale-Revised (CDRS-R) score of at least 40, and have received stable antidepressant treatment for at least 4 weeks.
Thirty participants will be randomized 1:1 to active or sham stimulation while continuing their current medication. The active group will receive 20 sessions over 4 weeks using the NEXALIN ADI device (77.5 Hz, 15 mA, approximately 40 minutes per session). The sham device will be identical in appearance but will deliver no current. Participants and operators will remain blinded.
Primary outcomes will include feasibility, acceptability, safety, and preliminary clinical efficacy. These will be examined through recruitment, treatment completion, follow-up retention, adverse events, and CDRS-R-defined response and remission. Secondary outcomes will assess depressive and anxiety symptoms, suicidality, sleep quality, global clinical status and improvement, rumination, and pediatric health-related quality of life. Exploratory outcomes will include THINC-it cognitive performance, magnetic resonance imaging, electroencephalography, functional near-infrared spectroscopy, eye tracking, facial expression features, and acoustic features.
Eligibility
Inclusion Criteria:
- Age 12-18 years.
- Meet DSM-5 diagnostic criteria for a current depressive episode, as confirmed by the K-SADS-PL.
- Children's Depression Rating Scale-Revised (CDRS-R) score ≥40 at baseline.
- Stable psychotropic medication treatment for at least 4 weeks prior to enrollment and willingness to continue the same regimen throughout the study.
Exclusion Criteria:
- Psychiatric comorbidities other than anxiety disorders.
- Depression with psychotic features.
- Young Mania Rating Scale (YMRS) score \>13.
- History of neurological disorders (e.g., epilepsy, traumatic brain injury) or severe physical illnesses (e.g., thyroid disease, lupus, diabetes, significant liver, kidney, or lung impairment, major trauma).
- Previous treatment with electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), tACS, or other neurostimulation therapies.
- Current use of antiepileptic drugs or high-dose benzodiazepines.
- History of alcohol or substance abuse or dependence.
- Pregnant or breastfeeding females.
- Contraindications to MRI.
- Current high suicide risk.
