Open Access

Miaoxi Chen, Simon Blackwell, Jonas Björklund, Lisa Feldmann, Wolfgang Strube, Lucia Bulubas, Ellen Greimel, Peter Bechmann, Frank Padberg, Gerrit Burkhardt

• Intermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for major depressive disorder (MDD) in adults. However, its effectiveness in younger populations remains understudied. The EARLY-BURST trial addresses this gap by assessing the efficacy and safety of iTBS targeting the left dorsolateral prefrontal cortex (lDLPFC) in adolescents and young adults seeking treatment for depressive disorders. The study utilizes an innovative sequential Bayesian, randomized, triple-blind, parallel-group, sham-controlled design. Up to 60 participants aged 16 to 26 years will be randomized to receive either active or sham iTBS, with data analyzed sequentially after 14 patients per group complete treatment. The primary outcome is the between-group difference in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 6, controlling for baseline MADRS scores. Since the trial's initiation in April 2024, fourIntermittent theta burst stimulation (iTBS), a form of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for major depressive disorder (MDD) in adults. However, its effectiveness in younger populations remains understudied. The EARLY-BURST trial addresses this gap by assessing the efficacy and safety of iTBS targeting the left dorsolateral prefrontal cortex (lDLPFC) in adolescents and young adults seeking treatment for depressive disorders. The study utilizes an innovative sequential Bayesian, randomized, triple-blind, parallel-group, sham-controlled design. Up to 60 participants aged 16 to 26 years will be randomized to receive either active or sham iTBS, with data analyzed sequentially after 14 patients per group complete treatment. The primary outcome is the between-group difference in scores on the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 6, controlling for baseline MADRS scores. Since the trial's initiation in April 2024, four participants have been enrolled, with an average age of 21.5 years, an average depression onset age of 16.5 years, and a mean baseline MADRS score of 25.5. Preliminary results indicate a significant reduction in depression severity across both groups, with a mean post-treatment MADRS score of 10. The EARLY-BURST trial not only investigates the potential of iTBS as an early intervention but also sets the stage for future adaptive platform trials to evaluate emerging and established rTMS protocols in youth populations. This trial represents a critical step toward refining therapeutic strategies in this rapidly evolving field. This trial is funded by the German Federal Ministry of Education and Research (BMBF) within the initial phase of the German Center for Mental Health (funding no. 01EE2303A).…