Study of a Repetitive Transcranial Magnetic Stimulation (rTMS) Device for the Treatment of Major Depressive Disorder

Inclusion Criteria:

• Primary diagnosis by DSM-IV criteria for Major Depressive Episode, single or recurrentepisode as confirmed by the Structured Clinical Interview for the DSM-IV (SCID-IV),with the additional stipulation of a duration for this episode of greater than orequal to 4 weeks and CGI-S greater than or equal to 4

• Duration of current episode of depression less than 3 years (the definition of anepisode is demarcated by a period of greater than or equal to 2 months when thepatient did not meet full criteria for the DSM-IV definition of major depressiveepisode);

• Total HAM-D17 score of greater than or equal to 20 and Item 1 score greater than orequal to 2 at screening visit;

• Medication resistance to at least two different antidepressant treatments, defined asresistance to a minimum of 1 and a maximum of 4 antidepressant drug trials of adequatedose and duration in the current episode with adequate dose and duration defined asminimum level 3 on the Antidepressant Treatment History Form (ATHF); or, if patienthas not received a sufficient number of antidepressant treatments to assess theirmedication resistance in the current episode, then the patient must meet level 3medication resistance by ATHF criteria to at least 1 and no more than 4 drug trials ina previous episode.

• Patients who have not completed antidepressant trials of adequate dose and durationdue to intolerance to therapy may be included if they have demonstrated intolerance togreater than or equal to 4 anti-depressant medications in the current or a previousepisode, and did not meet ATHF criteria for a single adequate treatment trial in thecurrent episode.

• Capable and willing to provide informed consent

• Signed HIPAA authorization

• Able to adhere with the treatment schedule, and withdrawal of ongoing pharmacotherapy

• If currently taking antidepressant pharmacotherapy, must be clinically appropriate todiscontinue treatment with those agents.

Exclusion Criteria:

• Investigators, site personnel directly affiliated with this study, and their immediatefamilies (immediate family is defined as a spouse, parent, child or sibling, whetherby birth or legal adoption);

• Individuals diagnosed by the Investigator with the following conditions (currentunless otherwise stated):

• Depression secondary to a general medical condition, or substance-induced;

• Seasonal pattern of depression as defined by DSM-IV

• History of substance abuse or dependence within the past year (except nicotineand caffeine)

• Any psychotic disorder (lifetime), including schizoaffective disorder, or majordepression with psychotic features in this or previous episodes

• Bipolar disorder

• Eating disorder (current or within the past year)

• Obsessive compulsive disorder (lifetime)

• Post-traumatic stress disorder (current or within the past year)

• An Axis II Personality Disorder, which in the judgment of the Investigator may hinderthe patient in completing the procedures required by the study protocol.

• Individuals with a clinically defined neurological disorder or insult including, butnot 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

• History of cerebrovascular accident

• Transient ischemic attack within two years

• Cerebral aneurysm

• Dementia

• Mini Mental Status Exam score of less than or equal to 24

• Parkinson's disease

• Huntington's chorea

• Multiple sclerosis

• Increased risk of seizure for any reason, including prior diagnosis of increasedintracranial pressure (such as after large infarctions or trauma), or history ofsignificant head trauma with loss of consciousness for greater than or equal to 5minutes

• A true positive response to any question on the Transcranial Magnetic StimulationAdult Safety Screen questionnaire

• Inability to locate and quantify a motor threshold as defined in the protocol

• ECT treatment within 3 months prior to the screening visit

• Failure to respond to ECT treatment (i.e., consistent with ATHF level 2 or higher) inthis or any previous episode

• History of treatment with rTMS therapy for any disorder

• History of treatment with Vagus Nerve Stimulation

• Use of any investigational drug within 4 weeks of the randomization visit

• Use of fluoxetine within 6 weeks of the randomization visit

• Use of an MAOI within 2 weeks of the randomization visit

• Use of any medication(s) listed on the Excluded Medication List within 1 week of therandomization visit

• Significant acute suicide risk, defined as follows:

• Suicide attempt within the previous 6 months that required medical treatment; or

• Greater than or equal to 2 suicide attempts in the past 12 months; or

• Has a clear-cut plan for suicide and states that he/she cannot guarantee thathe/she will call his/her regular psychiatrist or the Investigator if the impulseto implement the plan becomes substantial during the study; or

• In the Investigator's opinion, is likely to attempt suicide within the next 6months.

• Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstablecardiac disease;

• Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, orelectrodes) or any other metal object within or near the head, excluding the mouth,that cannot be safely removed

• Known or suspected pregnancy

• If participating in psychotherapy, must have been in stable treatment for at least 3months prior to entry into the study, with no anticipation of change in the frequencyof therapeutic sessions, or the therapeutic focus over the duration of the rTMS trial

• Positive urine drug screen. (A positive urine drug screen at screening may be repeatedonce prior to randomization)

• Clinically significant laboratory abnormality, in the opinion of the Investigator

• Women who are breast-feeding

• Women of child-bearing potential not using a medically accepted form of contraceptionwhen engaging in sexual intercourse.