Inclusion Criteria:  Male or female at the age of 18-75 years old at time of screening. Primary diagnosis of Major Depressive Disorder (without psychosis) based on DSM-5 criteria and MINI 7.0. MADRS score ≥22 No other causes of depressive symptoms other than MDD. Ability to read, understand and sign an informed consent document. Not more than 2 past failed pharmacologic interventions for the current depressive episode. If subject is female and at reproductive age, she must be tested negative for pregnancy. If subject is female and at reproductive age with childbearing potential (i.e., not post-menopausal or surgically sterilized) she must agree to use adequate birth control methods during the whole study duration.  Exclusion Criteria:  EXCLUSION CRITERIA  Patient is diagnosed with other major psychopathologies (i.e. schizophrenia, bipolar disorder, psychotic depression, geriatric depression). Patient requires antipsychotic medication or mood stabilizers (other than study medication), lithium, carbamazepine, valproate and other that may have an antidepressant effect. Electroconvulsive therapy (ECT) or transcranial magnetic stimulation therapy (TMS) conducted in the past or started within 90 days of screening or planned during the study. Nonpsychopharmacologic drugs with CNS effects that have been taken for less than 30 days prior to baseline. Subjects with a vagus nerve or deep brain stimulator. Patient is at substantial suicidal risk as determined by the Mini Neuropsychiatric Interview (MINI) Suicidality subscale for suicide attempts and/or judged by the treating physician. Patient has any current unstable medical condition or surgical illness. Patient has history of seizure or convulsions. A current status of dependence to a drug or alcohol. Inadequate communication with the patient. Patient has participated in another clinical study in the last 30 days preceding this study. In the investigator's judgement, patient is not able to provide written informed consent and follow protocol requirements. Pregnant women.