Major Depressive Disorder
Conditions
Keywords
Intermittent Theta Burst Stimulation, iTBS, Transcranial Magnetic Stimulation, Accelerated iTBS, Major Depressive Disorder
Brief summary
This randomized, rater-blinded clinical trial aims to compare the effectiveness, safety, and tolerability of accelerated intermittent theta burst stimulation (iTBS) with standard iTBS in adults with major depressive disorder (MDD). Participants will be randomly assigned in a 1:1 ratio to receive either accelerated or standard iTBS targeting the left dorsolateral prefrontal cortex. Participants may be psychotropic-medication naïve or may continue stable psychotropic medication according to the protocol-defined medication stability criteria. The accelerated iTBS group will receive 45 treatment sessions over approximately 15 treatment days, while the standard iTBS group will receive 20 treatment sessions over 4 weeks. The primary objective is to compare changes in depressive symptom severity, measured using the 17-item Hamilton Depression Rating Scale (HAM-D17), from baseline to the end-of-treatment assessment. Secondary and exploratory assessments include treatment response and remission, sleep quality, quality of life, cognitive measures, safety and tolerability, resting electroencephalography (EEG), and transcranial magnetic stimulation combined with EEG (TMS-EEG).
Interventions
Intermittent theta burst stimulation (iTBS) is delivered to the left dorsolateral prefrontal cortex using the Beam F3 approach. Stimulation consists of triplet bursts at 50 Hz repeated at 5 Hz, with 2 seconds on and 8 seconds off. Each session consists of 1,200 pulses delivered at 100% of the resting motor threshold. Participants receive three sessions per treatment day, separated by 30 ± 5-minute intervals, over 15 treatment days, for a total of 45 sessions.
DEVICEStandard Intermittent Theta Burst Stimulation
Intermittent theta burst stimulation (iTBS) is delivered to the left dorsolateral prefrontal cortex using the Beam F3 approach. Stimulation consists of triplet bursts at 50 Hz repeated at 5 Hz, with 2 seconds on and 8 seconds off. Each session consists of 600 pulses delivered at 120% of the resting motor threshold. Participants receive one session per treatment day, 5 days per week for 4 weeks, for a total of 20 sessions.
Sponsors
Military Hospital 175
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Outcome assessors will be blinded to treatment allocation. Participants and personnel administering the intervention will not be blinded because of differences in the treatment schedules. Participants will be instructed not to disclose their treatment allocation or treatment schedule to outcome assessors. Outcome assessors will not have access to randomization or treatment-allocation records.
Intervention model description
Participants with major depressive disorder are randomly assigned in a 1:1 ratio to one of two parallel active-treatment groups: accelerated intermittent theta burst stimulation (iTBS) or standard iTBS.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Age 18 to 65 years. * Right-handed. * Diagnosis of major depressive disorder according to ICD-10 criteria (F32 or F33), confirmed by a psychiatrist. * 17-item Hamilton Depression Rating Scale (HAM-D17) total score ≥18 at screening/baseline. * Able and willing to provide written informed consent and comply with essential study procedures. * Participants may be psychotropic-medication naïve or may be receiving psychotropic medication. Participants currently receiving psychotropic medication must have maintained the same medication(s) and dose(s) for at least 2 weeks before randomization; for fluoxetine, the required stable period is at least 4 weeks.
Exclusion criteria
* Intracranial or head/neck metallic foreign bodies or implants that constitute a contraindication to TMS or MRI. * Implanted electronic devices such as a cardiac pacemaker, implantable cardioverter-defibrillator, or deep brain stimulator. * Untreated or clinically unstable thyroid dysfunction based on abnormal TSH and/or free T4 levels. * Clinically significant intracranial structural abnormalities that may affect TMS safety, neuropsychiatric presentation, or study neurophysiological measures. * History of epilepsy or seizures, except febrile seizures in childhood. * Bipolar disorder. * Other major psychiatric disorders, including schizophrenia, delusional disorder, or eating disorders. * Acute suicide risk, defined as a score ≥3 on item 3 of the HAM-D17 or clear suicidal ideation or behavior. * Alcohol or substance abuse or dependence within the previous 6 months. * A medical condition associated with a high seizure risk or a history of cranial surgery. * Current use of medication judged by the screening physician to substantially increase seizure risk, or rapid reduction/discontinuation of benzodiazepines, antiseizure medications, or other centrally acting medications associated with withdrawal or increased seizure risk. * Serum vitamin D level \<20 ng/mL that has not been adequately corrected. * Elevated C-reactive protein associated with clinically significant acute infection or acute inflammatory illness that, in the investigator's judgment, may affect participant safety or study outcome assessment. * Pregnant or breastfeeding. * Unable to understand or complete essential study procedures. Participants with potentially reversible temporary exclusion conditions may be rescreened once the condition has been adequately corrected or clinically stabilized.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 17-Item Hamilton Depression Rating Scale (HAM-D17) Score From Baseline to End of Treatment | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Depressive symptom severity will be assessed using the 17-item Hamilton Depression Rating Scale (HAM-D17). The total score ranges from 0 to 52, with higher scores indicating greater depressive symptom severity. The primary outcome is the change in HAM-D17 total score from baseline (T0) to the end-of-treatment assessment (T4). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Response Based on HAM-D17 | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Treatment response is defined as a reduction of at least 50% in the 17-item Hamilton Depression Rating Scale (HAM-D17) total score from baseline. |
| Change in Sleep Quality Assessed by the Pittsburgh Sleep Quality Index (PSQI) | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Sleep quality is assessed using the Pittsburgh Sleep Quality Index (PSQI). The PSQI global score ranges from 0 to 21, with higher scores indicating poorer sleep quality. Change in PSQI global score from baseline to the end of treatment will be evaluated. |
| Change in Quality of Life Assessed by the WHOQOL-BREF | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Quality of life is assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF), which evaluates four domains: physical health, psychological health, social relationships, and environment. Each domain score is transformed to a 0-100 scale, with higher scores indicating better quality of life. Change in each domain score from baseline to the end-of-treatment assessment will be evaluated. |
| Change in Cognitive Function Assessed by the Montreal Cognitive Assessment (MoCA) | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Cognitive function is assessed using the Montreal Cognitive Assessment (MoCA). The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. Change in MoCA total score from baseline to the end of treatment will be evaluated. |
| Change in Cognitive Function Assessed by the Mini-Mental State Examination (MMSE) | Baseline (T0) and 24-72 hours after the final treatment session (T4) | Cognitive function is assessed using the Mini-Mental State Examination (MMSE). The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. Change in MMSE total score from baseline to the end of treatment will be evaluated. |
| Remission Based on HAM-D17 | End of treatment (T4), assessed 24-72 hours after the final treatment session | Remission is defined as a 17-item Hamilton Depression Rating Scale (HAM-D17) total score of 7 or less at the end of treatment. |
| Incidence of Adverse Events and Serious Adverse Events | From the first treatment session through the end-of-treatment assessment (T4) | Safety and tolerability will be assessed by monitoring adverse events (AEs) and serious adverse events (SAEs) throughout the treatment period. Adverse events potentially associated with iTBS, including headache, scalp discomfort, dizziness, and other reported adverse events, will be recorded. The number and proportion of participants experiencing at least one AE or SAE will be summarized by treatment group. |
Countries
Vietnam
Contacts
CONTACTDang Minh Ly, MD
Outcome results
None listed