EEG-Guided Transcranial Magnetic Stimulation for Adults With Depression

The purpose of this research is to see if an experimental treatment for depression called intermittent theta burst stimulation (iTBS), a form of transcranial magnetic stimulation (TMS) can be improved for better results using electroencephalography (EEG) recordings (brain waves) for individuals with Major Depressive Disorder (MDD). This is a feasibility study to test a "closed-loop" procedure which guides the timing of this FDA-cleared form of TMS. Each participant will receive an active experimental treatment, and the timing of the TMS pulses will be at one of three phases in the brain wave of interest.

Inclusion Criteria: * Outpatients * Voluntary patient seeking treatment with the capacity to consent * 22-60 years of age * Have Major Depressive Disorder (MDD) single or recurrent episodes confirmed with the Mini-International Neuropsychiatric Interview (MINI)57 * Failed to achieve a clinical response to an adequately dosed antidepressant as assessed with an Antidepressant Treatment History Form score of 3 or greater in the current episode or have had 2 separate trials of antidepressants that were intolerable * Have a score of 18 or higher on the Hamilton Depression Rating Scale (17 item) HDRS * In a current episode of MDD with duration of at least 4 weeks but less than 2 years * Have no initiation or dose change in any psychotropic medication or for the 4 weeks prior to screening * Have no clinically significant changes (as determined by the study investigators) in psychotherapeutic interventions for the 4 weeks prior to screening Can safely undergo TMS treatment based on the TMS Adult Safety Screen questionnaire * On a medically acceptable form of birth control if capable of becoming pregnant * Are able to adhere to the protocol and treatment schedule * Currently and throughout study participation is under the care of a licensed psychiatrist and/or other mental health care provider and agrees to promptly inform the investigator or study staff of any change in such provider(s). * Agrees to allow any and all forms of communication between the investigators and study staff with any healthcare provider who has provided service to the patient/participant within at least two years of study enrollment for the purposes of eligibility confirmation or in case of a safety event. * Agrees to provide the name and verifiable contact information (email and mailing addresses, mobile and land-line phone numbers, as applicable) of at least two persons 22 years or older who reside within reasonable driving time of the patient's home address. Participant also agrees that research personnel are at liberty to contact these individuals if the participant is unable to be contacted. Exclusion Criteria: * Have a history of a substance use disorder (including alcohol) * Within the past 3 months have a major medical illness, intracranial lesion or increased intracranial pressure, prior ischemic or hemorrhagic stroke, neurologic conditions with structural cerebral damage, stroke, multiple sclerosis, traumatic brain injury, epilepsy, a personal history of a seizure, or individuals with a family history of epilepsy or seizure in a first degree relative (please note that an individual with a first-degree relative with a history of epilepsy, or one or more seizures does not need to be excluded if the cause of epilepsy or seizure(s) is non-genetic (i.e., "non-idiopathic"), Alzheimer's and other neurodegenerative diseases, meningoencephalitis or intracerebral abscess, parenchymal or leptomeningeal cancers), moderate to severe heart disease, cardiac pacemaker, implanted devices, or implanted medication pumps * Contraindications for TMS or MRI * Have active suicidal intent, as determined by the Principal Investigator (PI) and/or is considered a moderate-high risk of suicide according to the Columbia-Suicide Severity Rating Scale (C-SSRS) Screen Version - Recent (i.e., answers YES to Question 3 and NO to Question 6 (Moderate risk) or YES to Question 4, 5, or 6 (High risk))4 by the PI. (Columbia Suicide Severity Rating Scale. * Pregnant and lactating patients * As determined by the Principal Investigator (PI), has: (a) a lifetime history of mania or hypomania symptoms from any cause; (b) a medical condition or diagnosis, within 1 year of screening, that seems somewhat likely to cause such symptoms; or (c) scores 12 on the Young Mania Rating Scale. * Based on the MINI interview have a lifetime diagnosis of bipolar I, bipolar II, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or any current psychotic symptoms. * Patients taking bupropion/Wellbutrin or antipsychotics are excluded