STUDY PROTOCOL article

Front. Neurol.

Sec. Neurotrauma

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1605157

This article is part of the Research TopicNeurological and Neuropsychiatric Disorders Affecting Military Personnel and Veterans - Volume IIView all 4 articles

Adaptive Trial for the Treatment of Depressive Symptoms Associated with Concussion using Accelerated Intermittent Theta Burst Stimulation (ADEPT): Rationale, Design and Methods

Provisionally accepted
  • 1National Institute of Mental Health (NIH), Bethesda, United States
  • 2Henry M Jackson Foundation for the Advancement of Military Medicine (HJF), Bethesda, Maryland, United States
  • 3Palo Alto Veterans Institute for Research, Palo Alto, California, United States
  • 4Department of Radiology and Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, Illinois, United States
  • 5VA Palo Alto Health Care System, Veterans Health Administration, United States Department of Veterans Affairs, Palo Alto, California, United States
  • 6Department of Neurosurgery, School of Medicine, Stanford University, Stanford, California, United States
  • 7Walter Reed National Military Medical Center, Bethesda, Maryland, United States
  • 8William Beaumont Army Medical Center, El Paso, Texas, United States
  • 9Arizona State University School of Medicine and Advanced Medical Engineering, Phoenix, Arizona, United States
  • 10Department of Psychiatry & Behavioral Sciences, School of Medicine, Duke University, Durham, North Carolina, United States
  • 11Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda, Illinois, United States

The final, formatted version of the article will be published soon.

Military service members (SMs) and veterans who have sustained one or more concussions during their service have significantly higher rates of persistent depressive symptoms and suicidality compared to non-injured peers. Despite over 500,000 SMs who have sustained concussions, there are currently no Level I evidence-based treatments for improving depressive symptoms associated with concussion. Accelerated intermittent theta burst stimulation (aiTBS), a specific repetitive transcranial magnetic stimulation (rTMS) protocol, targeted at the dorsolateral prefrontal cortex (DLPFC) has demonstrated efficacy and is cleared for the treatment of Major Depressive Disorder (MDD) by the United States Food and Drug Administration (FDA). The mechanism of action of aiTBS is thought to be via the modulation of functional networks. Herein we outline the design of a multisite, double-blind, randomized, sham-controlled trial of aiTBS for the treatment of depressive symptoms in SMs and veterans with a history of concussion. We present the rationale for this specific design and highlight the potential for personalized neuroimaging-informed parameter determination in this population where brain injuries have resulted in variable structural and functional brain circuitry disruptions.If successful, this project will accelerate solutions to improve the health, well-being, and healthcare of SMs and veterans with depressive symptoms following concussion.

Keywords: concussion, Major Depressive Disorder, Accelerated intermittent theta burst stimulation, Traumatic Brain Injury, Transcranial Magnetic Stimulation, Bayesian Adaptive Trial, military, resting state functional MRI

Received: 02 Apr 2025; Accepted: 27 May 2025.

Copyright: © 2025 Oberman, Penafiel, Dieterich, Phan, Chou, Pham, Adamson, Hines, Rezaee, Deng, Pal, Lisanby and Brody. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lindsay M Oberman, National Institute of Mental Health (NIH), Bethesda, United States

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