Intermittent theta burst stimulation (iTBS), a variant of repetitive transcranial magnetic stimulation (rTMS), is an established treatment for adults with major depressive disorder (MDD). Due to its favorable safety profile, iTBS is also a promising early intervention in the transition phase from adolescence to early adulthood, but this has not been systematically investigated to date. Thus, the EARLY-BURST trial investigates the efficacy and safety of iTBS over the left dorsolateral prefrontal cortex (lDLPFC) in treatment-seeking young patients (age 16–26 years) with depressive disorders (i.e. major depressive disorder, persistent depressive disorder, bipolar depression), allowing for relevant co-morbidities. Participants have not received antidepressant or antipsychotic medication during the last 12 months except for short-term (< 2 weeks) on-demand medication. The trial will employ a novel sequential Bayesian, randomized, double-blind, parallel-group, sham-controlled design. Up to 90 patients at two clinical sites (Munich, Augsburg) will be randomized 1:1 to the treatment groups, with sequential analyses starting after 26 patients in each group completed the treatment. The primary outcome will be the difference in depression severity at week 6 (post-treatment visit) between active iTBS and sham iTBS, assessed with the Montgomery-Åsberg Depression Rating Scale (MADRS). The trial is planned to be expanded towards a three-arm leapfrog design, contingent on securing additional funding. Thus, in addition to potentially providing evidence of iTBS’s efficacy in adolescents and young adults with depressive disorders, the EARLY-BURST trial aims at setting the stage for subsequent platform trials in this dynamic research field, where novel adaptive study designs are required to meet the need for rapidly testing promising new vs established rTMS protocols.
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, 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).
