rTMS to Target Neural Connectivity and Rumination in Treatment-Resistant Depression

Inclusion criteria

• Diagnosis of unipolar major depressive disorder without psychotic features by the Mini-International Neuropsychiatric Interview (MINI) and confirmed by study psychiatrist
• First depressive episode prior to age 50
• Current moderate to severe depression, Hamilton Depression Rating Scale (HDRS) ≥17)
• Failure to respond to ≥1 antidepressant medication at adequate dose and duration in the current depressive episode; (note: this criterion is designed to be consistent with the original 2008 FDA-labeled indication for TMS in Major Depressive Disorder, that specifies failure to respond to "one prior medication at or above the minimal effective dose and duration in the current episode" (https://www.accessdata.fda.gov/cdrh\_docs/pdf8/K083538.pdf). ))
• Off psychotropic medications OR on a stable dose of medication(s) for 6 weeks, and willing to remain on stable medication dosage throughout the study
• Capacity to consent
• Ability to safely receive MRI

Exclusion criteria

• Actively/imminently suicidal, Quick Inventory of Depressive Symptomatology (QIDS) item 12 score \>2)
• Current depressive episode duration \> 5 years
• Presence of clinically significant psychiatric diagnoses other than unipolar, non-psychotic major depression, such as post-traumatic stress disorder (PTSD) or obsessive-compulsive disorder (OCD)
• Evidence of cognitive impairment, Montreal Cognitive Assessment (MOCA) \< 23)
• Significant substance use disorder within past 6 months
• New-onset psychotherapy and/or somatic therapy (e.g., light therapy) within 6 weeks of screening
• Prior exposure to any form of TMS
• Have participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
• Failure to respond to Electroconvulsive therapy (ECT)
• Any history of neurosurgery to treat a neurologic or psychiatric disorder (e.g. Vagus nerve stimulation, cortical stimulation, deep brain stimulation, or ablative surgery)
• Unstable medical illness
• 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 (except juvenile febrile seizures or provoked seizures at the PI's discretion) or any condition/concurrent medication that could notably lower seizure threshold
• Pregnancy or planned pregnancy during the study
• Presence of cardiac pacemaker, cochlear implant, or other implanted electronic device
• Any vision problem that will prevent them from seeing the adjectives presented inside the MRI scanner without glasses