A naturalistic study comparing the efficacy of unilateral and bilateral sequential theta burst stimulation in treating major depression – the U-B-D study protocol

BMC Psychiatry

Study Protocol

Zafiris J. Daskalakis¹  Ram Brender²  Lisa McMurray²  Ruxandra Antochi²  Abir Gebara³  Jessica Drodge⁴  Jennifer Cuda⁴  Stacey Shim⁴  Youssef Nasr⁴  Antoinette Broomfield⁴  Nasim Kiaee⁵  Molly Watson⁵  Sara Tremblay⁶  Reggie Taylor⁷  Lauri Tuominen⁸  Alexandra Lemoyne⁹  Manon Desforges⁹  Noémie Landry⁹  Christophe Carleton⁹  Arthur R. Chaves^1,10 

[1] Department of Psychiatry, University California San Diego, 9500 Gilman Dr, 92093, La Jolla, CA, USA;Department of Psychiatry, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada;Royal Ottawa Mental Health Centre, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;School of Medicine, Stanford University, 300 Pasteur Drive, 94305, Stanford, CA, USA;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Department of Neuroscience, Carleton University, 1125 Colonel By Drive, K1S 5B6, Ottawa, ON, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Department of Neuroscience, Carleton University, 1125 Colonel By Drive, K1S 5B6, Ottawa, ON, Canada;Département de Psychoéducation Et Psychologie, Université du Québec en Outaouais, 283 Alexandre-Taché Boul, J8X 3X7, Gatineau, QC, Canada;Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Department of Physics, Carleton University, 1125 Colonel By Drive, K1S 5B6, Ottawa, ON, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Department of Psychiatry, University of Ottawa, 451 Smyth Road, K1H 8M5, Ottawa, ON, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Département de Psychoéducation Et Psychologie, Université du Québec en Outaouais, 283 Alexandre-Taché Boul, J8X 3X7, Gatineau, QC, Canada;University of Ottawa Institute of Mental Health Research at The Royal, 1145 Carling Ave, K1Z 7K4, Ottawa, ON, Canada;Faculty of Health Sciences, University of Ottawa, 125 University, K1N6N5, Ottawa, ON, Canada;

关键词: Major depressive disorder;    Transcranial magnetic stimulation (TMS);    Theta burst stimulation (TBS);    Magnetic resonance spectroscopy;    Evoked potential;    TMS-EEG;    Biomarkers;    Predictors of response;    Corticospinal excitability;    Resting state connectivity;   

DOI  :  10.1186/s12888-023-05243-4

 received in 2023-08-14, accepted in 2023-10-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMajor depressive disorder (MDD) is a prevalent mental health condition affecting millions worldwide, leading to disability and reduced quality of life. MDD poses a global health priority due to its early onset and association with other disabling conditions. Available treatments for MDD exhibit varying effectiveness, and a substantial portion of individuals remain resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS), applied to the left and/or right dorsolateral prefrontal cortex (DLPFC), is an alternative treatment strategy for those experiencing treatment-resistant MDD. The objective of this study is to investigate whether this newer form of rTMS, namely theta burst stimulation (TBS), when performed unilaterally or bilaterally, is efficacious in treatment-resistant MDD.MethodsIn this naturalistic, randomized double-blinded non-inferiority trial, participants with a major depressive episode will be randomized to receive either unilateral (i.e., continuous TBS [cTBS] to the right and sham TBS to the left DLPFC) or bilateral sequential TBS (i.e., cTBS to the right and intermittent TBS [iTBS] to the left DLPFC) delivered 5 days a week for 4–6 weeks. Responders will move onto a 6-month flexible maintenance phase where TBS treatment will be delivered at a decreasing frequency depending on degree of symptom mitigation. Several clinical assessments and neuroimaging and neurophysiological biomarkers will be collected to investigate treatment response and potential associated biomarkers. A non-inferiority analysis will investigate whether bilateral sequential TBS is non-inferior to unilateral TBS and regression analyses will investigate biomarkers of treatment response. We expect to recruit a maximal of 256 participants. This trial is approved by the Research Ethics Board of The Royal's Institute of Mental Health Research (REB# 2,019,071) and will follow the Declaration of Helsinki. Findings will be published in peer-reviewed journals.DiscussionComprehensive assessment of symptoms and neurophysiological biomarkers will contribute to understanding the differential efficacy of the tested treatment protocols, identifying biomarkers for treatment response, and shedding light into underlying mechanisms of TBS. Our findings will inform future clinical trials and aid in personalizing treatment selection and scheduling for individuals with MDD.Trial registrationThe trial is registered on https://clinicaltrials.gov/ct2/home (#NCT04142996).

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

Fig. 2

Fig. 1