Adolescent Biomarker Guided rTMS


About this study

The purpose of this study is to gather information regarding the use of rTMS as a treatment for depression in adolescents with Major Depressive Disorder. The investigators 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. 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Ages 12-18, male or female.
  • 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 will need to have stopped taking antidepressants at least 1 week prior (4 weeks for fluoxetine) to the baseline visit.
  • 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.

Inclusion Criteria - Healthy Controls:

  • Ages 12-18, male or female.

Exclusion Criteria:

  • The following psychiatric comorbidities are exclusionary:
    • psychotic disorders;
    • bipolar disorders;
    • anorexia nervosa;
    • bulimia nervosa;
    • 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.
  • 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.

Exclusion Criteria - Healthy Healthy Controls:

  • History of depression or any psychiatric treatment.
  • Subjects found to be pregnant at time of screening will be ineligible.
  • Positive urine drug screening.
  • Contraindications to MRI/MRS (CMRR Subject Safety Screening Form).

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Paul Croarkin, D.O., M.S.

Open for enrollment

Contact information:

Marjorie Gresbrink M.S.


More information


  • Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Read More on PubMed
  • Abnormalities in glutamate neurotransmission may have a role in the pathophysiology of adolescent depression. The present pilot study examined changes in cortical glutamine/glutamate ratios in depressed adolescents receiving high-frequency repetitive transcranial magnetic stimulation. Ten adolescents with treatment-refractory major depressive disorder received up to 30 sessions of 10-Hz repetitive transcranial magnetic stimulation at 120% motor threshold with 3000 pulses per session applied to the left dorsolateral prefrontal cortex. Baseline, posttreatment, and 6-month follow-up proton magnetic resonance spectroscopy scans of the anterior cingulate cortex and left dorsolateral prefrontal cortex were collected at 3T with 8-cm(3) voxels. Glutamate metabolites were quantified with 2 distinct proton magnetic resonance spectroscopy sequences in each brain region. After repetitive transcranial magnetic stimulation and at 6 months of follow-up, glutamine/glutamate ratios increased in the anterior cingulate cortex and left dorsolateral prefrontal cortex with both measurements. The increase in the glutamine/glutamate ratio reached statistical significance with the TE-optimized PRESS sequence in the anterior cingulate cortex. Glutamine/glutamate ratios increased in conjunction with depressive symptom improvement. This reached statistical significance with the TE-optimized PRESS sequence in the left dorsolateral prefrontal cortex. High-frequency repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex may modulate glutamate neurochemistry in depressed adolescents. Read More on PubMed
  • Noninvasive brain stimulation (NIBS) techniques such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (tCS) have the potential to mitigate a variety of symptoms associated with neurological and psychiatric conditions, including stroke, cerebral palsy, autism, depression, and Tourette syndrome. While the safety of these modalities has been established in adults, there is a paucity of research assessing the safety of NIBS among children. Read More on PubMed
  • Depressive disorders are among the most commonly experienced mental health concerns and a leading cause of mortality in adolescence. Current treatment guidelines recommend the use of antidepressant medication, cognitive behavioral therapy or both treatments. Unfortunately 40–60% of adolescents fail to respond to these treatments, therefore a new effective alternative treatment modality would be of particular benefit. rTMS is effective in addressing treatment resistant depression in adults and investigation into its effectiveness with adolescent populations has begun. Read More on PubMed
  • Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. Read More on PubMed
  • Transcranial magnetic stimulation (TMS) is emerging as a new treatment and neurophysiological research tool for psychiatric disorders. Recent publications suggest that this modality will also serve as a treatment and research tool in child and adolescent psychiatry. Current reports on therapeutic trials of repetitive transcranial magnetic stimulation (rTMS) in adolescents have primarily focused on depression. However, other pilot work involves the treatment of attention-deficit/hyperactivity disorder (ADHD), autism and schizophrenia. Neurophysiological studies typically utilize single and paired-pulse TMS paradigms which index cortical excitability and inhibition. Initial studies have focused on ADHD, autism, and depression. General knowledge regarding TMS among child and adolescent psychiatrists is lacking. The aim of this review is to provide an overview of TMS in the context of child and adolescent psychiatry, discuss recent therapeutic and neurophysiological studies, and examine relevant ethical considerations. Read More on PubMed
  • Depression is often a serious and debilitating illness in adolescents. Unfortunately, a significant number of adolescents do not respond to antidepressant medications or psychotherapy. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment intervention shown to benefit depression in adults. This study considered rTMS as an adjunctive treatment in adolescents with major depressive disorder. Read More on PubMed