The Effectiveness of rTMS in Depressed VA Patients

Inclusion Criteria:

   - Between 18 and 80 years of age

   - Using the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM)
   Disorders (SCID) for DSM-IV-TR (First et al. 2002) patients will be diagnosed Major
   Depressive Disorder (MDD).

   - Have a Hamilton Rating Scale for Depression (HRSD-24) score greater or equal to 20 no
   more than 7 days prior to randomization.

   - Exhibit moderate level of resistance to antidepressant treatment defined, using the
   Antidepressant Treatment History Form (ATHF) (Sackeim et al. 1990), as failure of at
   least two adequate medication trials.

   - Duration of current episode of less than or equal to 10 years.

   - Ability to obtain a Motor Threshold (MT) (should be determined at the end of the
   screening process).

   - Currently under the care of a VA psychiatrist.

   - If on a psychotropic medication regimen, that regimen will be stable for at least 4
   weeks prior to randomization and patient will be willing to remain on a stable regimen
   during the acute treatment phase.

   - Has an adequately stable condition and environment to enable attendance at scheduled
   clinic visits.

   - For female participants, agrees to use one of the following acceptable methods of
   birth control

      - Complete abstinence (not having sexual intercourse with anyone)

      - An oral contraceptive (birth control pills)

      - Norplant

      - Depo-Provera

      - A condom with spermicide

      - A cervical cap with spermicide

      - A diaphragm with spermicide

      - An Intrauterine device

      - Surgical sterilization (having tubes tied)

   - Able to read, verbalize understanding and voluntarily sign the Informed Consent Form
   prior to performance of any study-specific procedures or assessments.

Exclusion Criteria:

   - Pregnant or lactating female (This is an FDA-required exclusion. In the future, if
   rTMS becomes a proven treatment for major depression, its safety in the context of
   pregnancy should be studied separately (Nahas et al. 1999).

   - Unable to be safely withdrawn, at least two-weeks prior to treatment commencement,
   from medications that substantially increase the risk of having seizures. For the
   purpose of this study, those medications are listed in Appendix G (for example,
   theophylline).

   - Have a cardiac pacemaker.

   - Have an implanted device (deep brain stimulation) or metal in the brain.

   - Have a cochlear implant.

   - Have a mass lesion, cerebral infarct, increased intracranial pressure, or other active
   central nervous system (CNS) disease, including a seizure disorder.

   - Known current psychosis as determined by DSM-IV or SCID (axis I, psychotic disorder,
   schizophrenia) or a history of a non-mood psychotic disorder.

   - Known current Bipolar I disorder as determined by SCID or a History of Bipolar I
   disorder.

   - Current amnestic disorders, dementia, Blessed Orientation-Memory-Concentration (BOMC)
   greater than 10, delirium, or other cognitive disorders.

   - Current substance abuse (not including caffeine or nicotine) as determined by positive
   toxicology screen, or by history via SCID, within 3 months prior to screening.

   - Patients with an elevated risk of seizure due to traumatic brain injury (TBI).

   - Participation in another concurrent clinical trial.

   - Patients with prior exposure to rTMS.

   - Active current suicidal intent or plan as evidenced by a score of 4 or 5 on the
   suicidal ideation portion of the Columbia Suicide Severity Rating Scale (C-SSRS) or
   the endorsement of an actual attempt, interrupted attempt, or an aborted attempt in
   the past 6 months. All patients will be required to establish a written safety plan
   involving their primary psychiatrist and the treatment team before entering the
   clinical trial (See Section X.B.8).

   - Unstable cardiac disease or recent (< 3 months previous) myocardial infarction.

   - Patient refuses to sign consent for participation in the study.