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 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.

Exclusion criteria

• 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);
• 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
• Space occupying brain lesion
• Any history of seizure EXCEPT those therapeutically induced by Electroconvulsive T Therapy (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 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.
• Any self-inflicted harm in the past 3 months not in the context of suicidal ideation.
• 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).
• Individuals who have cardiac pacemakers or active implantable electrodes/neurostimulators within 30 cm of the treatment coil.
• 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
• 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 of contraception when engaging in sexual intercourse.