Synchronized Transcranial Magnetic Stimulation (sTMS) in Major Depressive Disorder

Inclusion Criteria

• Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major Depressive Disorder by DSM-IV-TR criteria rendered by structured interview using the Mini International Neuropsychiatric Interview (MINI).
• HAM-D17 score >= 17 and Item 1 score greater than or equal to 2.
• Duration of current episode >=8 weeks. The definition of an episode is demarcated by a period of >=2 months when the subject did not meet full criteria for the DSM-IV-TR definition of Major Depressive Episode. Maximum duration of current episode cannot exceed 2 years.
• The baseline EEG is of sufficient duration and quality that it can be processed for quantitative analysis.
• Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.

Exclusion Criteria

• Subjects are unable or unwilling to give informed consent.
• Diagnosed with the following conditions (current unless otherwise stated):
• Any other current primary Axis I mood, anxiety, or psychotic disorder, including bipolar disorder.
• Depression secondary to a general medical condition, or substance-induced.
• History of substance abuse or dependence within the past 6 months (except nicotine and caffeine).
• Any bipolar disorder or psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in this or previous episodes.
• Eating disorder (current or within the past year).
• Obsessive compulsive disorder (lifetime).
• Post-traumatic stress disorder (current or within the past year).
• ADHD (currently being treated).
• Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR criteria, which in the judgment of the Investigator may hinder the subjects in completing the procedures required by the study protocol.
• Subjects with a clinically defined neurological disorder 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 ECT (childhood febrile seizures are acceptable and these subjects may be included in the study).
• History of stroke.
• Transient ischemic attack within two years.
• Cerebral aneurysm.
• Dementia.
• Mini Mental Status Exam (MMSE-2) score of =<24.
• Parkinson's disease.
• Huntington's disease.
• Multiple sclerosis.
• Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold. Medications that lower the seizure threshold are included in the Prohibited Concomitant Medication (Section 5.7).
• Subjects who are currently hospitalized due to severity of depression symptoms.
• Subjects with any of the following treatment histories:
• TMS treatment within 6 months prior to the screening visit.
• ECT treatment within 1 year prior to the screening visit.
• Failure to respond to TMS or ECT treatment (i.e., consistent with ATHF confidence level 3 or higher) in this or any previous episode.
• Lifetime history of treatment with Deep Brain Stimulation or Vagus Nerve Stimulation.
• Use of any investigational drug or device within 4 weeks of the randomization visit.
• Subjects who have been treated with fluoxetine within the past four weeks.
• If participating in psychotherapy, must have been in stable treatment for at least 2 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 trial.
• Failure to respond to Monoamine Oxidase Inhibitors (MAOIs) in the current episode.
• Use of any medication(s) listed on the Prohibited Concomitant Medication within 1 week of randomization.
• Subjects are adequately benefiting from current antidepressant medication(s).
• Significant acute suicide risk, defined as:
• Suicide attempt within the previou