Burkhardt Gerrit, Blackwell Simon E, Chen Miaoxi, Feldmann Lisa, Björklund Jonas, Dechantsreiter Esther, Bulubas Lucia, Goerigk Stephan, Keeser Daniel, Falkai Peter, Greimel Ellen, Bechmann Peter, Schulte-Körne Gerd, Hasan Alkomiet, Strube Wolfgang, Padberg Frank
Department of Psychiatry and Psychotherapy, LMU University Hospital, Munich, Germany.
German Center for Mental Health (DZPG), Partner Site Munich-Augsburg, Munich, Germany.
Eur Arch Psychiatry Clin Neurosci. 2024 Oct 10. doi: 10.1007/s00406-024-01926-5.
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.
间歇性θ波爆发刺激（iTBS）是重复经颅磁刺激（rTMS）的一种变体，是治疗成人重度抑郁症（MDD）的既定疗法。由于其良好的安全性，iTBS也是从青春期到成年早期过渡阶段有前景的早期干预措施，但迄今为止尚未进行系统研究。因此，EARLY - BURST试验研究了iTBS对左侧背外侧前额叶皮质（lDLPFC）进行治疗的、患有抑郁症（即重度抑郁症、持续性抑郁症、双相抑郁症）的年轻患者（年龄16 - 26岁）的疗效和安全性，允许存在相关合并症。参与者在过去12个月内未接受过抗抑郁药或抗精神病药物治疗，但短期（<2周）按需用药除外。该试验将采用一种新颖的序贯贝叶斯随机双盲平行组假对照设计。两个临床地点（慕尼黑、奥格斯堡）的多达90名患者将按1:1随机分配到治疗组，每组26名患者完成治疗后开始序贯分析。主要结局将是在第6周（治疗后访视）时，使用蒙哥马利 - 阿斯伯格抑郁评定量表（MADRS）评估的主动iTBS与假iTBS之间抑郁严重程度的差异。该试验计划根据获得额外资金的情况扩展为三臂跨越式设计。因此，EARLY - BURST试验除了可能提供iTBS对患有抑郁症的青少年和年轻人疗效的证据外，还旨在为这一动态研究领域的后续平台试验奠定基础，在该领域需要新颖的适应性研究设计来满足快速测试有前景的新rTMS方案与既定方案的需求。试验注册号：DRKS00033313。
