Neuronavigated aiTBS for TRD

Exclusion Criteria

• •Psychiatric Exclusions:
• •1. Any psychiatric disorder other than MDD and comorbid anxiety disorders, including but not limited to:
• •(i) Bipolar disorder (Type I or II) (ii) Schizophrenia spectrum or other psychotic disorders (iii) Post-traumatic stress disorder (PTSD) (iv) Attention-deficit/hyperactivity disorder (ADHD) (v) Autism spectrum disorder (ASD) (vi) Obsessive-compulsive disorder (OCD) (vii) Current DSM-5 substance-use disorder (abuse or dependence) within the past 6 months, except nicotine dependence
• •2. Personality disorder confirmed on clinical interview by an experienced study psychiatrist
• •3. Severe suicidal ideation with structured plan (HDRS-17 item 3 score \>2) or as determined by the evaluating psychiatrist
• •4. Depressive symptoms better explained by another psychiatric condition, a medical condition, substance use, or use of medications
• •Medical and Neurological Exclusions:
• •1. Any neurological disorder including but not limited to:
• •(i) History of seizure disorder or epilepsy (ii) Family history of epilepsy (first-degree relatives) (iii) Significant head trauma with loss of consciousness \>5 minutes (iv) Stroke or transient ischemic attack (v) Neurodegenerative disorders (e.g., Parkinson's disease, multiple sclerosis, dementia) (vi) Brain tumor or intracranial mass lesion
• •2. Unstable medical condition, defined as any condition requiring acute medical intervention or hospitalization within the past 3 months, or any condition that in the investigator's judgment could affect participant safety or study outcomes
• •Contraindications to TMS/MRI:
• •1. Presence of ferromagnetic material in or near the head, including:
• •(i) Intracranial implants (e.g., aneurysm clips, shunts, stimulators) (ii) Cochlear implants or hearing aids (iii) Metallic facial tattoos or permanent makeup (iv) Other implanted medical devices deemed unsafe for MRI/TMS
• •2. Inability to tolerate MRI scanning due to claustrophobia or other reasons
• •Medication Exclusions:
• •Current use of medications known to significantly alter cortical excitability:
• •1. Anticonvulsants (including those used for mood stabilization)
• •2. Psychostimulants
• •3. Lithium
• •4. Benzodiazepines exceeding 10mg diazepam-equivalent daily dose
• •Prior Treatment Exclusions:
• •1. Electroconvulsive therapy (ECT) (≥ 6 sessions) in the current depressive episode
• •2. Ketamine or esketamine treatment (≥ 6 sessions) in the current depressive episode
• •3. Use of rTMS/iTBS (≥ 15 sessions) during the current depressive episode
• •4. Vagus nerve stimulation (VNS) or deep brain stimulation (DBS) implantation
• •Psychotherapy:
• •Concurrent evidence-based psychotherapy is permitted if initiated \>4 weeks prior to enrollment and maintained at stable frequency throughout the tria
• •Other reasons:
• •1. Unable to adhere to the study visit schedule
• •2. Planning to relocate outside the study catchment area during the trial period
• •3. No reliable transportation to attend study visits
• •4. Current participation in another research study
• •5. Current pregnancy (confirmed by in interview and clinical evaluation and, if deemed necessary, urine pregnancy test at screening)
• •6. Currently breastfeeding