Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

Inclusion Criteria: * Male or female, 22 to 80 years of age. * Able to provide informed consent. * Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major Depressive Episode (MDE). * Participants may currently be on a stable and adequate dose of SSRI antidepressant therapy. Participants may choose to not be on antidepressant therapy for the study duration, or to be switched from other classes to a medication from the SSRI class. * Participants may also have a history of intolerance to at least 2 antidepressant medications. These patients with the intolerance history will not be required to be currently taking an antidepressant medication. * Participants must qualify as "Moderately Treatment Refractory" or "High Treatment Refractory" using the Maudsley staging method. * Meet the threshold on the total HAMD17 score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * Meet the threshold on the total MADRS score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * Meet the threshold on the total BDI-II score of \>/=20 at both screening and baseline visits (Day -5/-14 and Day 0). * In good general health, as ascertained by medical history. * If female, a status of non-childbearing potential or use of an acceptable form of birth control. The form of birth control will be documented at screening and baseline. * Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone) will be allowed if the therapy has been stable for at least 4 weeks prior to screening and if it is expected to remain stable. Exclusion Criteria: * Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study. * Female that is pregnant or breastfeeding. * Female with a positive pregnancy test at participation. * Total HAMD17 score of \< 20 at the screen or baseline visits. * Total MADRS score of \< 20 at the screen or baseline visits. * Total BDI-II score of \< 20 at the screen or baseline visits. * Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by DSM-IV-TR), with the exception of nicotine dependence, at screening or within six months prior to screening. * Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of the participant's treatment for the past six months or more). * History of schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes. * Any Axis I or Axis II Disorder, which at screening is clinically predominant to their MDD or has been predominant to their MDD at any time within six months prior to screening. * Considered at significant risk for suicide during the course of the study. * Cognitive impairment (as noted by previous diagnoses-including dementia). * Has a clinically significant abnormality on the screening examination that might affect safety, study participation, or confound interpretation of study results. * Participation in any clinical trial with an investigational drug or device within the past month or concurrent to study participation. * Any current or past history of any physical condition which in the investigator's opinion might put the subject at risk or interfere with study results interpretation. * History of positive screening urine test for drugs of abuse at screening: cocaine, amphetamines, barbiturates, opiates. * Current (or chronic) use of opiates. * History of epilepsy. * History of rTMS exposure. * History of any implanted device or psychosurgery for depression. * Any history of ECT (greater than 8 sessions) without meeting responder criteria * History of shrapnel or metal in the head or skull. * "Low Treatment Refractory" using the Maudsley staging method. * History of cardiovascular disease or cardiac event. * History of OCD. * History of autism spectrum disorder. * History of intractable migraine * History of independent sleep disorder.