The overall objective of this current study is to evaluate the feasibility, safety, and tolerability of "high dose" aiTBS in psychiatric inpatient and outpatients with treatment-refractory unipolar, non-psychotic major depressive disorder, using patients receiving ECT as an active comparator. Developing a better understanding of the feasibility and tolerability of adapting this treatment to an acutely ill patient population could lead to huge breakthroughs for clinician decision-making and for the further optimization of brain stimulation depression protocols. The results of this study can help guide future confirmatory efficacy trials of high-dose aiTBS by providing a better understanding of how feasibility, safety and tolerability compare to ECT, as well as unforeseen challenges of its use.

Inclusion Criteria:

• • Ability to provide informed consent

  • Availability for the duration of the study and willingness to comply with all study procedures
  • Age 18 to 90
  • Diagnosis of major depressive disorder by DSM-5 criteria
  • Depressive symptoms are thought to be caused primarily by a major depressive episode and not by some other neurologic or psychiatric illness
  • Failure of or intolerance to at least 2 antidepressant treatments of different therapeutic classes (can include psychotherapy trial or neurostimulation trial)
  • Meets criteria for clinical eligibility for ECT treatment, including optimization of any medical conditions and completion of any medical testing or clearance as clinically indicated
  • Able to consent voluntarily to treatment
  • Score of at least 2 on the MADRS item 10
  • Ability to sit or lie down for an extended period of time and willingness to adhere to the theta burst stimulation protocol

Exclusion Criteria:

• • Presence of implanted ferromagnetic devices or materials, including cardiac pacemaker, cochlear implant, deep brain stimulation device, vagus nerve stimulation device, shrapnel, facial or scalp piercings that cannot be removed, or metallic face or head tattoos

  • Pregnancy or lactation
  • Previous bad reaction or intolerance to transcranial magnetic stimulation
  • Febrile illness within 1 week
  • Treatment with another investigational drug or other intervention within 30 days
  • Recent substance abuse or use disorder within the past 6 months, excluding tobacco or infrequent cannabis use
  • History of epilepsy or seizure disorder
  • History of penetrating traumatic brain injury, multiple sclerosis, or history of brain surgery or intracranial hemorrhage
  • Primary psychiatric or medical/neurologic illness other than MDD that is more likely to account for depressive symptoms, including severe personality disorder or psychotic illness
  • Severe or moderate intellectual disability
  • Major neurocognitive disorder
  • Involuntary commitment or petition filed for involuntary ECT treatment

Investigator and outcomes assessor will be blinded to patient's designation.