Efficacy and Safety of Accelerated Intermittent Theta-burst Stimulation (a-iTBS) in Adolescents With Depressive Disorder

Efficacy and Safety of Accelerated Intermittent Theta-burst Stimulation (a-iTBS) in Adolescents With Depressive Disorder: A Randomized, Double-Blind, Controlled Pilot Study

This study aims to assess the feasibility, safety, acceptability, and preliminary efficacy trends of a Accelerated Intermittent Theta-burst Stimulation (a-iTBS) intervention for adolescent depression through a pilot clinical trial. The findings will inform the design and optimization of subsequent formal randomized controlled trials, providing essential evidence for their execution.

This study is a randomized, double-blind, controlled pilot trial aimed at evaluating the feasibility, safety, acceptability, and preliminary efficacy trends of Accelerated Intermittent Theta-burst Stimulation (a-iTBS) for the treatment of adolescent depression.

Adolescents diagnosed with Major Depressive Disorder (MDD) will be randomly assigned in a 1:1:1 ratio to one of three groups: the experimental target a-iTBS treatment group, the conventional target a-iTBS treatment group, and the sham stimulation group. All three groups will receive 10 consecutive days of a-iTBS stimulation (5 Hz, 90% RMT) or sham stimulation intervention, using the Blackdolphin TMS Robot (SLD-YXRJ) by Xi'an Solide Brain Modulation Ltd. Co., with 50 sessions in total. The intervention frequency and procedure will remain consistent across all groups.

In the experimental target a-iTBS treatment group, participants will undergo MRI-guided identification of the left dorsolateral prefrontal cortex (DLPFC) region, where the voxel most negatively correlated with the functional connectivity of the subgenual anterior cingulate cortex (sgACC) will serve as the stimulation target. In the conventional target a-iTBS treatment group, participants will have the standard F3 target in the DLPFC identified via MRI guidance as the stimulation site. Participants in the sham stimulation group will receive a placebo treatment, simulating the a-iTBS procedure without generating an effective magnetic field output.

The primary outcome of the treatment phase is the efficacy rate or the remission rate of depressive symptoms. Secondary outcomes include symptom scales, anxiety symptoms, suicide risk, quality of life, sleep, rumination, and cognition. Safety will be monitored through adverse events, vital signs, laboratory tests, and tolerability assessments.

Inclusion Criteria:

(1) Age 12 - 18 (2) Diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), confirmed through the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime version (K-SADS-PL), currently in a depressive episode (3) Score≥40 on the CDRS-R (4) Stable pharmacological treatment: At least 4 weeks of stable psychiatric medication use prior to enrollment, with continuation of the same psychiatric medication regimen throughout the study.

-

Exclusion Criteria:

1. Psychiatric comorbidities other than anxiety disorders
2. Depression with psychotic symptoms
3. Young Mania Rating Scale (YMRS) score >13
4. A history of neurological disorders (e.g., epilepsy, brain injury) or severe somatic diseases (e.g., thyroid disorders, lupus, diabetes, pulmonary, hepatic, or renal impairment, major trauma)
5. Patients currently using anticonvulsants or high-dose benzodiazepines
6. A history of electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), or other neuromodulation treatments
7. A history of alcohol or substance abuse or dependence
8. Women who are pregnant or breastfeeding
9. Current high suicide risk
10. Potential complicating factors related to transcranial magnetic stimulation, such as scalp conditions or perforations that may affect magnetic field delivery
11. Contraindications to MRI -