New Investigational Stimulation Protocol for Treatment of Major Depression Disorder (MDD)

Inclusion Criteria:

• Outpatients.

• Men and women 22-68 years of age.

• Primary Diagnostic and Statistical Manual (DSM-V) diagnosis of Major Depression,single or recurrent episode confirmed by the Quick Structured Clinical Interview forthe DSM-5 Disorders (QuickSCID-5), with the additional requirements of a currentepisode ≥4 weeks and CGI-S ≥4.

• Current depressive episode is less than 5 years in duration (the definition of anepisode is demarcated by a period of ≥2 months in which the patient did not meetfull criteria for the DSM-V definition of major depressive episode);

• Total HDRS-21 ≥20 and Item 1 score ≥2 at the screening visit;

• The patient did not respond to at least one antidepressant treatment, i.e., aminimum of 1 and a maximum of 4 antidepressant drug trials, of adequate dose andduration (defined as a minimum level of 3 on the Antidepressant Treatment HistoryForm - Short Form (ATHF-SF)) in the current episode; or Patients who have notcompleted antidepressant trials of adequate dose and duration (defined as a level of 1-2 on the ATHF-SF) due to intolerance to therapy, if they have demonstratedintolerance to 2 or more antidepressant medications in the current episode.

• Capable and willing to provide informed consent

• Able to adhere to the treatment schedule.

• Patient is stable on medication for 2 month and is not expected to change medicationduring the study period.

• Satisfactory safety screening questionnaire for transcranial magnetic stimulation.

Exclusion Criteria:

• Investigators, site personnel directly affiliated with this study, and theirimmediate families (immediate family is defined as a spouse, parent, child orsibling, whether by birth or legal adoption);

• Individuals diagnosed by the Investigator with the following conditions (currentunless otherwise stated):

• Depression secondary to a general medical condition, or substance-induced;

• Substance abuse disorder within the past 3 months (except nicotine and caffeine).Note that use of cannabis for medical reasons in a stable regimen is permitted aslong as the investigator excludes abuse of the substance.

• Any psychotic disorder (lifetime), including schizoaffective disorder or majordepression with psychotic features or Bipolar disorder.

• Post-traumatic stress disorder (current or within the past year)

• Current (within 12 months of baseline) generalized anxiety disorder, panic disorderor social anxiety disorder as assessed by the investigator to be primary, causing ahigher degree of distress or impairment than MDD.

• Presence (within 12 months of baseline) of a personality disorder (such asantisocial, schizotypal, histrionic, borderline, narcissistic) as assessed by theinvestigator to be primary, causing a higher degree of distress or impairment thanMDD.

• Individuals with a significant neurological disorder or insult including (but notlimited to):

• Any condition likely to be associated with increased intracranial pressure

• Space occupying brain lesion

• Any history of seizure EXCEPT those therapeutically induced by Electroconvulsive TTherapy (ECT) or febrile seizures

• History of cerebrovascular accident

• Transient ischemic attack within two years

• Cerebral aneurysm

• Dementia

• Mini Mental State Exam score of less than or equal to 24

• Parkinson's disease

• Huntington's chorea

• Multiple sclerosis

• Individuals with a first-degree relative family history of seizure.

• ECT treatment within 3 months prior to the screening visit

• History of treatment with Vagus Nerve Stimulation (VNS)

• History of treatment with Deep Brain Stimulation (DBS)

• Use of any investigational drug within 4 weeks of the baseline visit

• Present suicidal risk as assessed by the investigator or significant suicide riskbased on HDRS-21 item 3 score of 3 or 4, or significant suicide risk as assessedusing the Scale for Suicide Ideation (SSI), or a history of attempted suicide in thelast year.

• Any self-inflicted harm in the past 3 months not in the context of suicidalideation.

• Conductive, ferromagnetic or other magnetic-sensitive metals implanted in the head (excluding the mouth) or within 10 cm of the treatment coil (e.g., cochlearimplants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bulletfragments, shrapnel, surgical clips, fragments from welding or metal work).

• Individuals who have cardiac pacemakers or active implantableelectrodes/neurostimulators within 30 cm of the treatment coil.

• If participating in psychotherapy, must have been in stable treatment for at least 3months prior to entry into the study, with no anticipation of change in thefrequency of therapeutic sessions, or the therapeutic focus over the duration of therTMS trial

• Clinically significant medical condition in the opinion of the Investigator.

• Known or suspected pregnancy

• Women who are breast-feeding

• Women of childbearing potential and not using a medically accepted form ofcontraception when engaging in sexual intercourse.