rTMS for Depressed Teens: A Sham-Controlled Trial, Part 1

Part 1 of the study aims to:

- Evaluate the antidepressant effects of daily, active rTMS (when compared with sham
treatment) in adolescents meeting criteria for Major Depressive Disorder, single or
recurrent episode.

- Evaluate, by proton magnetic resonance spectroscopy (1H-MRS) at 3 Tesla(3T),
neurometabolic biomarkers at the beginning and end of each study phase.

- Define regional specificity [anterior cingulate (AC) and left dorsolateral
prefrontal cortex (L-DLPFC)] of cerebral metabolites(i.e. glutamate and glutamine)
in adolescent depression.

- Study whether specific neurochemical resonances are associated with response,
remission, and/or maintenance of improvement of clinical depressive symptoms when
rTMS is used to treat adolescent depression.

Inclusion Criteria:

- Diagnosis of unipolar major depressive disorder, in a current major depressive
episode, without psychotic features

- Pretreatment CDRS-R Raw score ≥ 40

- Age is at least 12 and less than 22 years

- Ongoing, stable dose antidepressant therapy for at least 6 weeks to include the
following antidepressants (with dosing range):

- Celexa (citalopram hydrobromide) - 10 to 60mg

- Cymbalta (duloxetine) - 40mg to 120mg

- Desyrel (trazodone HCl) - 12.5mg to 150mg

- Effexor (venlafaxine HCl) - 37.5mg to 300mg

- Luvox (fluvoxamine maleate) - 25mg to 200mg

- Lexapro (escitalopram oxalate) - 10mg to 40mg

- Paxil (paroxetine HCl) - 10mg to 50mg

- Pristiq (desvenlafaxine) - 50mg to 100mg

- Prozac (fluoxetine HCl) - 10mg to 80mg

- Remeron (mirtazapine) - 7.5mg to 45mg

- Savella (milnacipran HCl) - 25mg to 200mg

- Zoloft (sertraline HCl) - 25mg to 200mg

- Subjects able to attend at least 31 study visits at study site.

- Willing to provide informed assent (adolescent) and informed consent (family)

Exclusion Criteria:

- Subjects currently on stimulant, antipsychotic, bupropion or tricyclic antidepressant
medications.

- Prior rTMS, vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT)

- Contraindication to MRI

- Contraindication to rTMS (history of neurological disorder such as seizures, increased
intracranial pressure, brain surgery, or head trauma with loss of consciousness for
>15 minutes, history of stroke, family history of epilepsy, intracardiac lines,
Anticoagulant, immune suppressive and/or chemotherapy, or those who received any of
these therapies within 3 months before enrollment in the study Unstable medication
conditions such as hematological or infectious (e.g., human immunodeficiency
virus-HIV) disorders, implanted electronic device, metal in the head, or pregnancy)

- History of schizophrenia, schizoaffective disorder, other [non mood disorder]
psychosis, depression secondary to a medical condition, mental retardation, substance
dependence or abuse within the past year (except nicotine), bipolar disorder,
psychotic features in this or previous episodes, amnestic disorder, obsessive
compulsive disorder, post-traumatic stress disorder, panic disorder

- History of autoimmune, endocrine, viral, or vascular disorder.

- Unstable cardiac disease, uncontrolled hypertension, or sleep apnea

- Active suicidal intent or plan, or history of attempt within the past 6 months