Using brain connectivity to guide rTMS treatment for depression

Inclusion Criteria:

* Age 22 to 65 years
* Major Depressive Disorder (by M.I.N.I., Diagnostic Statistical Manual V (DSM-V criteria)); Verification by evaluation by licensed study psychiatrist or psychologist
* At least moderately severe depression (17-item Hamilton Depression Rating Scale greater than or equal to 18)
* Failure to respond in the current episode to at least 1 antidepressant medication at an adequate dose and duration as measured by a modified Antidepressant Treatment History Form. The Maudsley Staging Method will also be used to quantify treatment resistance.
* Any and all medication intended to treat depression or reduce symptoms of depression must be discontinued or maintained at the same daily dose for ≥ 4 weeks prior to enrollment and for the duration of the study
* Capacity to consent
* Written consent to allow communication between members of the research team and the patient's outpatient clinician(s) (psychiatrist, psychotherapist, nurse practitioner, primary care physician, or equivalent) as needed to ensure safety
* Ability to safely participate in MRI
* Fluent in English

Exclusion Criteria:

* Imminent risk of suicide (based on the Columbia-Suicide Severity Rating Scale)
* Current depressive episode greater than or equal to 2 years duration
* Presence of primary psychiatric diagnoses other than MDD and/or comorbid generalized anxiety disorder (GAD) or phobia (e.g., post-traumatic stress disorder; obsessive-compulsive disorder; MDD w psychotic features; primary psychotic illness; Bipolar I or II)
* DSM-5 defined addiction to, dependence on, abuse of, or misuse of any substance during the prior 12 months, excluding nicotine
* Evidence of cognitive impairment (MMSE score falling greater than or equal to 1 SD below the mean score for his or her age and education)
* Recent onset (within 8 weeks of screening) psychotherapy, including, but not limited to: any form of treatment, aid, or therapy that has intensively and extensively examined the patient's psychological history, including, but not limited to: cognitive behavioral therapy, dialectical behavioral therapy, interpersonal therapy, and family-focused therapy
* Prior exposure to an adequate dose and duration of the TMS treatment protocol administered in this study during the current depressive episode.
* Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
* History of neurosurgery to treat a neurological or psychiatric disorder
* Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor), epilepsy, history of seizures, cerebrovascular disease, dementia, increased intracranial pressure, history of repetitive or severe head trauma, or primary or secondary tumors within the central nervous system
* Implanted electronic devices and/or conductive objects in or near the head, including metal plates, aneurysm coils, cochlear implants, ocular implants, deep brain stimulation devices and stents
* Any implanted device that is activated or controlled in any way by physiological signals, including, but not limited to: deep brain stimulators, cochlear implants, and vagus nerve stimulators
* Patients with major depressive disorder who have failed to receive clinical benefit from Vagus Nerve Stimulation (VNS) or are currently receiving these therapies.
* History of seizures (except juvenile febrile seizures) or any condition/concurrent medication that could notably lower seizure threshold
* Individuals who are pregnant, nursing, contemplating pregnancy within the length of the study or, in the opinion of the investigator, not adherent to a medically acceptable method of birth control
* History or presence of any disease, medical condition or physical condition that, in the opinion of the investigator, may compromise, interfere, limit, effect, or reduce the participant's ability to complete a treatment study lasting up to 21 weeks
* Abnormal bloodwork for electrolytes, thyroid and liver function
* Individuals who are taking \> 300 mg daily dose of bupropion in any formulation (immediate, extended, or slow-release)
* Individuals who are taking tricyclic antidepressants.