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 MajorDepressive Episode (MDE).
• Participants may currently be on a stable and adequate dose of SSRI antidepressanttherapy. Participants may choose to not be on antidepressant therapy for the studyduration, 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 antidepressantmedications. These patients with the intolerance history will not be required to becurrently taking an antidepressant medication.
• Participants must qualify as "Moderately Treatment Refractory" or "High TreatmentRefractory" using the Maudsley staging method.
• Meet the threshold on the total HAMD17 score of >/=20 at both screening and baselinevisits (Day -5/-14 and Day 0).
• Meet the threshold on the total MADRS score of >/=20 at both screening and baselinevisits (Day -5/-14 and Day 0).
• Meet the threshold on the total BDI-II score of >/=20 at both screening and baselinevisits (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 ofbirth 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 screeningand if it is expected to remain stable.

Exclusion Criteria:

• Female of childbearing potential who is not willing to use one of the specified formsof 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 byDSM-IV-TR), with the exception of nicotine dependence, at screening or within sixmonths prior to screening.
• Current diagnosis of Axis I disorders other than Dysthymic Disorder, GeneralizedAnxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or SpecificPhobia (unless one of these is comorbid and clinically unstable, and/or the focus ofthe participant's treatment for the past six months or more).
• History of schizophrenia or schizoaffective disorders, or any history of psychoticsymptoms in the current or previous depressive episodes.
• Any Axis I or Axis II Disorder, which at screening is clinically predominant to theirMDD or has been predominant to their MDD at any time within six months prior toscreening.
• 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 mightaffect safety, study participation, or confound interpretation of study results.
• Participation in any clinical trial with an investigational drug or device within thepast month or concurrent to study participation.
• Any current or past history of any physical condition which in the investigator'sopinion 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.