Inclusion Criteria:
* DSM-5 diagnosis of major depressive disorder confirmed using the Mini International Neuropsychiatric Interview (MINI30) Axis 1 and mood modules
* Treatment-resistant MDD during the current major depressive episode documented in the MGH Antidepressant Treatment History Questionnaire (ATRQ31), which will be defined as being non-responders (less than 50% of symptom improvement) to two or more depression treatment trials of adequate dose and duration as defined by the MGH ATRQ.
* At least moderate depression severity, operationalized as Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20
Exclusion Criteria:
* Ever met criteria for a psychotic disorder (Sz, SzAff, Bipolar disorder)
* Anorexia nervosa or bulimia nervosa within the last year
* Unstable medical condition by history, physical exam or laboratory results
* Currently pregnant or breastfeeding women; fecund women not using adequate contraceptive methods or with plan to become pregnant
* Contraindications to MRI (based on metal screening form)
* Meets criteria for claustrophobia
* Recent drug or alcohol use disorder with DSM-5 specifier of moderate or severe within 6 months, or mild within 2 months; or lifetime history of IV drug use A- ctively suicidal, as defined by expressive ideation with a plan or with suicidal ideation that requires immediate medical or treatment intervention.
* Neurological or neuromuscular disorder
* Requires medications for a general medical condition that contraindicate the TMS treatment
* Prior non-response to ECT, vagal nerve stimulation (VNS) or deep brain stimulation (DBS)
* History of ketamine treatment within 6 months
* History of monoamine oxidase inhibitor (MAOI) within the past month
* Lacks capacity to consent
* Taking medications that increase the risk of seizures.
* For patients on permitted concomitant psychotropic agents (antidepressants, anticonvulsants, benzodiazepines, hypnotics, opiates, triiodothyronine (T3), modafinil, psychostimulants, buspirone, melatonin, omega-3 fatty acids, folate, l-methylfolate, s-adenosyl methionine, lithium) dosing must be stable for at least four weeks prior to study entry and patients must agree to continue at the same dose during the study
