Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression

The Researchers are going to gather information regarding the use of rTMS as a treatment for depression in adolescents with Major Depressive Disorder. The researchers also hope to learn if measures of brain activity (cortical excitability and inhibition) collected with transcranial magnetic stimulation (TMS) can be used to identify which patients will benefit from certain types of rTMS treatment.

Phase I is a double-blind, randomized, biomarker-stratified trial of 1 Hz vs. 10 Hz rTMS. Phase II is for participants who do not respond to Phase I treatment and is a biomarker guided, double-blind trial of continuous vs intermittent theta burst stimulation (TBS). Please note that transcranial magnetic stimulation (TMS) biomarkers will be collected in this protocol during the course of the proposed interventions. Participants in Phase I will be offered enrollment in a separate protocol with baseline and posttreatment 7 Tesla Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) scans

Eligibility Criteria:
Inclusion Criteria:

* Depressed adolescent participants will have a primary diagnoses of MDD based on a clinical and structured interview with the MINI
* Depression symptoms severity of a 40 or greater based on evaluation with the Children's Depression Rating Scale Revised (CDRS-R) at screening and baseline visits. Further, the total score of the baseline CDRS-R score must not have had a 25% or greater decrease from the screening CDRS-R score
* The duration of the current episode of depression must be 4 weeks or more but 3 years or less.
* For any participant currently receiving antidepressant medication, the referring clinician must determine that insufficient benefit is being received from this treatment and it is clinically appropriate to discontinue the existing antidepressant.
* Participants in psychotherapy are eligible provided that this was initiated 4 weeks prior to enrollment and that the frequency of visits will be maintained during study participation.

Exclusion criteria:

* The following psychiatric comorbidities are exclusionary: psychotic disorders, bipolar disorders, anorexia nervosa, bulimia nervosa, and substance use disorders within the past year (with the exception of caffeine and tobacco)
* A positive urine drug screen at baseline
* Seizure history
* Family history of epilepsy in a first degree relative
* Head trauma with loss of consciousness for greater than 5 minutes
* Any true positive findings on the rTMS safety screening form.
* Any concurrent psychotropic medications (for potential participants receiving antidepressants or psychotropic medications, the referring clinician must determine that insufficient benefit is being received from the treatment and if clinically appropriate, discontinue existing antidepressants and other psychotropic medications)
* Prohibited concomitant medications (See Appendix A)
* Pregnancy or suspected pregnancy in female Participants (assessed with urine pregnancy test)
* Conductive, ferromagnetic, or other magnetic-sensitive metals implanted in the subject's head within 30 cm of the treatment coil excluding the mouth that cannot safely be removed. Examples include cochlear implants, implanted electrodes/stimulators, aneurysm clips or coils, stents, bullet fragments, jewelry and hair barrettes.
* Prior brain surgery
* Risk for increased intracranial pressure such as a brain tumor
* Any unstable medical condition
* History of treatment with ECT or TMS Therapy for any disorder
* Use of any investigational drug within 4 weeks of the baseline visit
* Initiation of a new psychotherapeutic treatment within the past 4 weeks
* Suicide attempt within the previous 6 months that required medical treatment or ≥ 2 attempts in the past 12 months, or has a clear cut plan for suicide and states that he/she cannot guarantee that he/she will inform a family member or call his/her psychiatrist or the investigator if the impulse to implement the plan becomes substantial during the study; or, in the investigator's opinion, is likely to attempt suicide within the next 6 months.