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. 2025 Sep;275(6):1827-1838.
doi: 10.1007/s00406-024-01926-5. Epub 2024 Oct 10.

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials

Gerrit Burkhardt  1   2 , Simon E Blackwell  3 , Miaoxi Chen  4   5 , Lisa Feldmann  6   5 , Jonas Björklund  4   5 , Esther Dechantsreiter  4   5 , Lucia Bulubas  4   5 , Stephan Goerigk  4   7   5 , Daniel Keeser  4   5 , Peter Falkai  4   5 , Ellen Greimel  6   5 , Peter Bechmann  5 , Gerd Schulte-Körne  6   5 , Alkomiet Hasan  8   5 , Wolfgang Strube  8   5 , Frank Padberg  4   5
Affiliations

Intermittent theta burst stimulation in adolescents and young adults with depressive disorders: protocol of a randomized, sham-controlled study with a sequential Bayesian design for adaptive trials

Gerrit Burkhardt et al. Eur Arch Psychiatry Clin Neurosci. 2025 Sep.

Abstract

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.Trial registration: DRKS00033313.

Keywords: Adaptive trial design; Adolescents; Depression; Major depressive disorder; Theta burst stimulation; Transcranial magnetic stimulation.

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Conflict of interest statement

Declarations. Conflict of interest: GB, SB, MC, LF, JB, AK, ED, LB, SG, DK, EG, PB, and GS report no competing interests. WS has received a paid speakership from Mag & More (neurocare), Recordati and Rovi. He was member of advisory boards of Recordati, Janssen and Boehringer Ingelheim. Invitations to conferences or other activities were not accepted. AH is editor of the German (DGPPN) schizophrenia treatment guidelines, first author of the WFSBP schizophrenia treatment guidelines; on advisory boards of and speaker fees from AbbVie (speaker fees only), Advanz (speaker fees only), Janssen-Cilag, Lundbeck, Recordati, Rovi, and Otsuka. PF received research support/honoraria for lectures or advisory activities from Boehringer-Ingelheim, Janssen, Lundbeck, Otsuka, Recordati and Richter; he has received and is currently receiving grants from several national and international foundations and institutions, e.g. from the “German Science Foundation”, the “German Ministry of Science” and the “German Ministry of Health”. FP has received grants from the German Research Foundation (BR 4264/6–1) and the German Federal Ministry of Education and Research (01EW1903); consulting fees from Brainsway (Jerusalem, Israel) as a member of the European Scientific Advisory Board and from Sooma (Helsinki, Finland) as a member of the International Scientific Advisory Board; honoraria for workshops from Mag&More (Munich, Germany) and honoraria for lectures from the NeuroCare Group and Brainsway; and has received equipment from Mag&More, the NeuroCare Group, and Brainsway.

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