Efficacy and Safety of a Theta Burst Stimulation Protocol of Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Depression

A Prospective, Multicenter, Randomized, Single-Blind, Exploratory Clinical Trial to Validate the Efficacy and Safety and Predict Treatment Response of a Theta Burst Stimulation Protocol of Repetitive Transcranial Magnetic Stimulation in Treatment-Resistant Depression

This study will evaluate the efficacy and safety of a theta burst stimulation (TBS) protocol of repetitive transcranial magnetic stimulation (rTMS) in adults with treatment-resistant depression. Participants will be randomized to either antidepressant treatment plus active rTMS TBS or antidepressant treatment plus sham stimulation for the first 10 sessions followed by active rTMS TBS for the next 10 sessions. The main objective is to compare the change in Hamilton Depression Rating Scale (HAM-D) total score after 10 treatment sessions between groups and to explore predictors of treatment response.

This is a prospective, multicenter, randomized, double-blind, exploratory clinical trial evaluating the efficacy and safety of rTMS theta burst stimulation (TBS) in patients with depression.

A total of 120 participants will be enrolled, including 80 adults (≥19 years) with treatment-resistant depression and 40 adolescents (15-17 years) with depressive disorders. Participants will be stratified by age group and randomized in a 1:1 ratio to one of two treatment arms.

In the combined treatment arm, participants will receive antidepressant therapy plus active bilateral sequential TBS (bsTBS) for 20 sessions over approximately 4 to 7 weeks. In the comparator arm, participants will receive antidepressant therapy plus sham stimulation for the first 10 sessions, followed by active TBS for the remaining 10 sessions.

The primary outcome is the change in depressive symptom severity after 10 treatment sessions, measured by HAM-D in adults and age-appropriate scales in adolescents. Secondary outcomes include sleep, cognitive function, global clinical improvement, social functioning, and neuroimaging biomarkers. Safety outcomes include adverse events and suicidal ideation assessments.

This study aims to explore the efficacy of TBS across different age groups and to identify predictors of treatment response.

Inclusion Criteria:

• Age ≥15 years
• Diagnosis of depressive disorder based on DSM criteria
• Adults: treatment-resistant depression
• Adolescents: depressive disorder requiring treatment
• Moderate or greater depressive symptoms
• Adults: HAM-D ≥17, MADRS ≥14
• Adolescents: age-appropriate validated scale (e.g., CDRS-R)
• Currently receiving or eligible for antidepressant treatment

Exclusion Criteria:

• Bipolar disorder, schizophrenia, or psychotic disorder
• Substance use disorder (recent)
• Neurological disorders (e.g., epilepsy, brain injury)
• Severe medical illness
• Metal implants or contraindications to TMS
• Pacemaker or implanted device
• Prior rTMS or ECT
• Pregnancy
• Any condition deemed unsuitable by investigator