A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression.

Objective: Research and clinical application of transcranial magnetic stimulation (TMS) for adolescents with major depressive disorder has advanced slowly. Significant gaps persist in the understanding of optimized, age-specific protocols and dosing strategies. This study aimed to compare the clinical effects of 1-Hz vs 10-Hz TMS regimens and examine a biomarker-informed treatment approach with glutamatergic intracortical facilitation (ICF).

Method: Participants with moderate-to-severe symptoms of major depressive disorder were randomized to 30 sessions of left prefrontal 1-Hz or 10-Hz TMS, stratified by baseline ICF measures. The primary clinical outcome measure was the Children's Depression Rating Scale-Revised (CDRS-R). The CDRS-R score and ICF biomarker were collected weekly.

Results: A total of 41 participants received either 1-Hz (n = 22) or 10-Hz (n = 19) TMS treatments. CDRS-R scores improved compared with baseline in both 1-Hz and 10-Hz groups. For participants with low ICF at baseline, the overall least squares means of CDRS-R scores over the 6-week trial showed that depressive symptom severity was lower for participants treated with 1-Hz TMS than for participants who received 10-Hz TMS. There were no significant changes in weekly ICF measurements across 6 weeks of TMS treatment.

Conclusion: Low ICF may reflect optimal glutamatergic N-methyl-d-aspartate receptor activity that facilitates the therapeutic effect of 1-Hz TMS through long-term depression-like mechanisms on synaptic plasticity. The stability of ICF suggests that it is a tonic, traitlike measure of N-methyl-d-aspartate receptor-mediated neurotransmission, with potential utility to inform parameter selection for therapeutic TMS in adolescents with major depressive disorder.

Clinical Trial Registration Information: Biomarkers in Repetitive Transcranial Magnetic Stimulation (rTMS) for Adolescent Depression; https://clinicaltrials.gov; NCT03363919.

Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list.