Cortical Inhibition as a Biomarker of Response in a Comparison of Bilateral Versus Unilateral Accelerated Theta Burst Stimulation for Suicidal Ideation in Treatment-Resistant Depression -COMBAT-SI

Inclusion criteria

• 18-70 years old.
• Diagnosis of major depressive episode, confirmed on Mini-International Neuropsychiatric Interview (MINI), with HRSD score ≥18.
• Ongoing SI present beyond screening phase of study (confirmed with Beck SSI score ≥4).
• Pass the TMS adult safety screening (TASS) questionnaire and the MRI safety screening questionnaire.
• Have failed to achieve a clinical response to an adequate dose of two antidepressants based on an Antidepressant Treatment History Form (ATHF) score for each antidepressant trial of \> 3 in the current episode OR have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (ATHF score of 1 or 2 on those 2 separate antidepressants) OR have a combination of one failed trial and one not tolerated trial, per the definitions above.
• Psychiatric illness due to a general medical condition (GMC) has been ruled out during initial assessment.
• Voluntary outpatients capable to consent to treatment and seen at the UC San Diego Health Interventional Psychiatry program.
• Able to adhere to the treatment schedule.

Exclusion criteria

• Have a confirmed diagnosis of substance use disorder within the last 3 months.
• Have a lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
• Have a diagnosis of obsessive compulsive disorder, post-traumatic stress disorder (current or within the last year), anxiety disorder (generalized anxiety disorder, social anxiety disorder, panic disorder), or dysthymia, that is assessed by a study investigator to be primary and causing greater impairment than MDD.
• Have a diagnosis of any personality disorder, and assessed by a study investigator to be primary and causing greater impairment than MDD.
• Have SI prompting emergent involuntary hospital stay (SI in which the participant can maintain voluntary and capable outpatient status as well as recent suicide attempt will not be exclusionary).
• Currently pregnant or lactating, or woman or childbearing age without adequate birth control.
• Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
• Not capable to consent to treatment and/or not suitable for outpatient treatment.
• Have a concomitant major unstable medical illness, cardiac pacemaker or implanted medication pump; Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT or a febrile seizure of infancy, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, significant head trauma with loss of consciousness for greater than 5 minutes; Have an intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
• Currently take more than lorazepam 2 mg daily (or equivalent) or any dose of an anticonvulsant due to the potential to limit rTMS efficacy.