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

Prior treatment

• 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
• Conductive, ferromagnetic or other magnetic-sensitive metals implanted in the head (excluding the mouth) or within 10 cm of the treatment coil (e.g., cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, shrapnel, surgical clips, fragments from welding or metal work).
• If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the rTMS trial

Other illness

• Individuals diagnosed by the Investigator with the following conditions (current unless 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 as long as the investigator excludes abuse of the substance.
• Any psychotic disorder (lifetime), including schizoaffective disorder or major depression 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 disorder or social anxiety disorder as assessed by the investigator to be primary, causing a higher degree of distress or impairment than MDD.
• Presence (within 12 months of baseline) of a personality disorder (such as antisocial, schizotypal, histrionic, borderline, narcissistic) as assessed by the investigator to be primary, causing a higher degree of distress or impairment than MDD.
• Individuals with a significant neurological disorder or insult including (but not limited to):
• Any condition likely to be associated with increased intracranial pressure
• Any history of seizure EXCEPT those therapeutically induced by Electroconvulsive T Therapy (ECT) or febrile seizures
• History of cerebrovascular accident
• Dementia
• Parkinson's disease
• Individuals with a first-degree relative family history of seizure.
• Present suicidal risk as assessed by the investigator or significant suicide risk based on HDRS-21 item 3 score of 3 or 4, or significant suicide risk as assessed using the Scale for Suicide Ideation (SSI), or a history of attempted suicide in the last year.
• Individuals who have cardiac pacemakers or active implantable electrodes/neurostimulators within 30 cm of the treatment coil.
• Clinically significant medical condition in the opinion of the Investigator.

Other

• Investigators, site personnel directly affiliated with this study, and their immediate families (immediate family is defined as a spouse, parent, child or sibling, whether by birth or legal adoption);
• Space occupying brain lesion
• Transient ischemic attack within two years
• Cerebral aneurysm
• Mini Mental State Exam score of less than or equal to 24
• Huntington's chorea
• Multiple sclerosis
• Any self-inflicted harm in the past 3 months not in the context of suicidal ideation.
• Known or suspected pregnancy
• Women who are breast-feeding
• Women of childbearing potential and not using a medically accepted form of contraception when engaging in sexual intercourse.

• 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 for the DSM-5 Disorders (QuickSCID-5), with the additional requirements of a current episode ≥4 weeks and CGI-S ≥4.
• Current depressive episode is less than 5 years in duration (the definition of an episode is demarcated by a period of ≥2 months in which the patient did not meet full 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., a minimum of 1 and a maximum of 4 antidepressant drug trials, of adequate dose and duration (defined as a minimum level of 3 on the Antidepressant Treatment History Form - Short Form (ATHF-SF)) in the current episode; or Patients who have not completed 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 demonstrated intolerance 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 medication during the study period.
• Satisfactory safety screening questionnaire for transcranial magnetic stimulation.