Repetitive Transcranial Magnetic Stimulation for Adolescent Major Depressive Disorder: A Focus on Neurodevelopment

Adolescent depression is a potentially lethal condition and a leading cause of disability for this age group. There is an urgent need for novel efficacious treatments since half of adolescents with depression fail to respond to current therapies and up to 70% of those who respond will relapse within 5 years. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising treatment for major depressive disorder (MDD) in adults who do not respond to pharmacological or behavioral interventions. In contrast, rTMS has not demonstrated the same degree of efficacy in adolescent MDD. We argue that this is due, in part, to conceptual and methodological shortcomings in the existing literature. In our review, we first provide a neurodevelopmentally focused overview of adolescent depression. We then summarize the rTMS literature in adult and adolescent MDD focusing on both the putative mechanisms of action and neurodevelopmental factors that may influence efficacy in adolescents. We then identify limitations in the existing adolescent MDD rTMS literature and propose specific parameters and approaches that may be used to optimize efficacy in this uniquely vulnerable age group. Specifically, we suggest ways in which future studies reduce clinical and neural heterogeneity, optimize neuronavigation by drawing from functional brain imaging, apply current knowledge of rTMS parameters and neurodevelopment, and employ an experimental therapeutics platform to identify neural targets and biomarkers for response. We conclude that rTMS is worthy of further investigation. Furthermore, we suggest that following these recommendations in future studies will offer a more rigorous test of rTMS as an effective treatment for adolescent depression.