Neuroimaging in Patients Undergoing TMS for Depression

General Inclusion Criteria:

1. Male or female outpatients, 18 to 60 years of age.
2. Primary diagnosis of Major Depressive Disorder as confirmed by the Structured Clinical Interview for Diagnostic and Statistical Manual (DSM-IV-TR) Disorders (SCID-IV-TR).
3. Duration of the index episode of at least 1 month.
4. MDD symptoms, defined as a total HDRS-17 score ≥ 18 despite treatment with an adequate trial of a serotonin reuptake inhibitor (SRI).
5. Individuals who cannot tolerate medications.
6. Patients currently on medication must be at the same stable dose(s) for 1 month prior to enrollment and be willing to continue at the same dose(s) through the duration of the study.
7. Capable and willing to provide informed consent.
8. Signed HIPAA authorization.
9. Right-handed.
10. Willingness to undergo research fMRI scan (3T).
11. Willingness to undergo randomization to either treatment arm.

General Exclusion Criteria:

1. Investigators, and their immediate families (defined as a spouse, parent, child or sibling, whether by birth or legal adoption).
2. Individuals diagnosed by the investigators with the following conditions: Bipolar Disorder (lifetime), any Psychotic Disorder (lifetime), history of substance abuse or dependence within the past year (except nicotine and caffeine).
3. Behavior, which in the judgment of the investigator may hinder the patient in completing the procedures required by the study protocol.
4. Individuals with a clinically defined neurological disorder including, but not limited to: tics, space occupying brain lesion; any history of seizures except those therapeutically induced by electroconvulsive therapy (ECT); history of cerebrovascular accident; history of fainting; transient ischemic attack within two years; cerebral aneurysm, Dementia; Parkinson's Disease; Huntington chorea; Multiple Sclerosis.
5. Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or history of significant head trauma with loss of consciousness for ≥ 5 minutes.
6. Use of any investigational drug within 12 weeks of the randomization visit.
7. Significant acute suicide risk, defined as follow: suicide attempt within the previous 6 months that required medical treatment; or ≥ 2 suicide attempts in the past 12 months; or in the investigator's opinion, has significant risk for suicide based on the current state or recent history.
8. Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease.
9. Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed.
10. Current illicit drug use (cannabinoid, phencyclidine, amphetamines, barbiturates, cocaine, methadone, and opiates), defined as drug use during the 6 months before screening.
11. Known or suspected pregnancy. Urine pregnancy test Women who are breast-feeding.
12. Women of childbearing potential not using a medically accepted form of contraception when engaging in sexual intercourse.
13. Medicinal patch, unless removed prior to the magnetic resonance (MR) scan.
14. MDD patients with very severe depression, defined as a total HDRS-17 score ≥ 23, will be excluded and referred to immediate treatment.
15. Risks related to seizures, such as substance abuse or sleep disruptions/insomnia.

SpecificExclusion criteria (group 1):

History of treatment with rTMS therapy for any disorder.

Specific Inclusion criteria (group 2):

History of non-response to rTMS in this depressive episode.