Inclusion Criteria:
1. Outpatients with non-psychotic, unipolar Major Depressive Disorder (MDD) assessed via the MINI structured interview
2. Must have been on a stable dose of antidepressant medication (excluding tricyclic antidepressants) for at least 1 month prior to randomization, and with significant residual MDD symptoms as evidenced by a HamD17 score \> 17;
3. If receiving medication other than for depression (e.g., anxiety, sleep, mood stabilization), must have been on stable dose for at least 1 month prior to randomization
4. A history of treatment failure with at least one adequate trial of an antidepressant medication in the current episode, assessed by the Antidepressant Treatment and History Form
5. Age range: 22-65.
Exclusion Criteria:
1. Patient is mentally or legally incapacitated, unable to give informed consent.
2. Patients with psychosis (psychotic depression, schizophrenia, or schizoaffective diagnoses (lifetime)); bipolar disorder (lifetime); dementia (lifetime); current Mini Mental State Examination ≤ 24; delirium or substance abuse within the past 6 months; eating disorder within the past year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within the past year; acute risk for suicide or self-injurious behavior. Patients with diagnostic uncertainty or ambiguity (e.g. rule-out pseudodementia of depression) will be excluded.
3. Patients with a HamD suicidality item score of '3' or '4,' corresponding to "suicidal ideas or gestures" or "attempts at suicide," will be excluded.
4. Patients with exposure to Electroconvulsive Therapy within the past 6 months, previous TMS treatment for any condition, or Vagus Nerve Stimulation treatment (lifetime).
5. Patients who have met diagnostic criteria for any current substance abuse disorder at any time in the 6 months prior to enrollment.
6. Past history of skull fracture; cranial surgery entering the calvarium; space occupying intracranial lesion; stroke, Cerebral Vascular Accident, or Transient Ischemic Attacks; cerebral aneurysm; Parkinson's or Huntington's disease; or Multiple Sclerosis.
7. Any history of intracranial implant including cochlear implant, implanted electrodes/stimulators, aneursym clips or coils, stents, bullet fragments; implanted cardiac pacemaker, defibrillator, vagus nerve stimulator, deep brain stimulator; or other implanted devices or objects contraindicated by product labeling.
8. Neurological conditions including epilepsy, cerebrovascular disease, dementia, increased intracranial pressure, history of repetitive or severe head trauma, or with primary or secondary tumors in the Central Nervous System.
9. current pregnancy, breast feeding, or not using a medically accepted means of contraception.
10. Infection or loss of integrity of skin over the forehead, where the device will be positioned.
11. Increased risk of seizure as indicated by: a) history (or family history) of seizure or epilepsy; b) history of stroke, head injury, or unexplained seizures; c) concurrent medication use such as tricyclic antidepressants, neuroleptic medications, or other drugs that are known to lower the seizure threshold; d) secondary conditions that may significantly alter electrolyte balance or lower seizure threshold; e) no quantifiable motor threshold such that TMS dosage cannot be accurately determined.
12. Other medical contraindications to any of the study procedures.
