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

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

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.