Accelerated Versus Standard Intermittent Theta Burst Stimulation for Major Depressive Disorder

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.