Subthreshold stimulation intensity is associated with greater clinical efficacy of intermittent theta-burst stimulation priming for Major Depressive Disorder
Abstract
Background: Intermittent theta-burst stimulation priming (iTBS-P) can improve clinical outcome of patients with Major Depressive Disorder (MDD) who do not show early benefit from 10 Hz stimulation of left dorsolateral prefrontal cortex (DLPFC), also known as high-frequency left-sided (HFL) stimulation. The intensity and pulse number for iTBS-P needed to induce clinical benefit have not been systematically examined. Objective: To study the effect of intensity and pulse number on the clinical efficacy of iTBS-P. Methods: We conducted a retrospective review of 71 participants who received at least five sessions of HFL with limited clinical benefit and received iTBS-P augmentation for between 5 and 25 sessions. Intensity of iTBS-P priming stimuli ranged from 75 to 120% of motor threshold (MT) and pulse number ranged from 600 to 1800. Associations among intensity, pulse number, and clinical outcome were analyzed using a mixed methods linear model with change in IDS-SR as the primary outcome variable, priming stimulation intensity (subthreshold or suprathreshold), pulse number (<1200 or >1200 pulses), and gender as fixed factors, and number of iTBS-P treatments and age as continuous covariates. Results: Subjects who received subthreshold intensity iTBS-P experienced greater reduction in depressive symptoms than those who received suprathreshold iTBS-P (p = 0.011) with no effect of pulse number after controlling for stimulus intensity. Conclusions: Subthreshold intensity iTBS-P was associated with greater clinical improvement than suprathreshold stimulation. This finding is consistent with iTBS-P acting through homeostatic plasticity mechanisms.
Additional Information
© 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Received 16 March 2021, Revised 14 June 2021, Accepted 15 June 2021, Available online 23 June 2021. The authors would like to acknowledge the patients and their families who received treatment in the clinic during the study period, and the dedication of the technicians and administrative team that have made this work possible. This project was made possible by the Ryan Family Fund for TMS Research. We thank the Ryan Family for their generous support of innovative approaches to depression treatment and of groundbreaking TMS technology. Their contributions have advanced the university's education and research missions through their support of the Neuromodulation Division. CRediT authorship contribution statement: Jonathan C. Lee: was involved in, Conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, preparing, writing and editing the manuscript, Visualization, and project administration. Juliana Corlier: was involved in conceptualization, Methodology, and editing the manuscript. Andrew C. Wilson: was involved in conceptualization, Methodology, Validation, Formal analysis, Software, Visualization, review and editing, and project administration. Reza Tadayonnejad: was involved in conceptualization, Methodology, and editing the manuscript. Katharine G. Marder: was involved in data curation and editing the manuscript. Doan Ngo: was involved in data curation and validation. David E. Krantz: was involved in data curation and editing the manuscript. Scott A. Wilke: was involved in data curation and editing the manuscript. Jennifer G. Levitt: was involved in data curation and editing the manuscript. Nathaniel D. Ginder: was involved in data curation and editing the manuscript. Andrew F. Leuchter: was involved in conceptualization, Methodology, Validation, Formal analysis, Investigation, Data curation, preparing, writing and editing the manuscript, Resources, Supervision, Project administration, Funding acquisition. Declaration of competing interest: Drs. Corlier, Tadayonnejad, Marder, Krantz, Wilke, Levitt, and Ginder, along with Ms. Doan Ngo have no disclosures, Andrew Wilson has served as a consultant to HeartCloud, Inc within the past 36 months. Dr. Leuchter discloses that within the past 36 months he has received research support from the National Institutes of Health, Neuronetics, Department of Defense, CHDI Foundation, and NeuroSigma, Inc. He has served as a consultant to NeoSync, Inc., Ionis Pharmaceuticals, Inc., and ElMindA. He is Chief Scientific Officer of Brain Biomarker Analytics LLC (BBA). Dr. Leuchter has equity interest in BBA. Jonathan Lee has received in-kind equipment support from Magventure Inc. The authors report no other conflicts of interest in this work.Attached Files
Published - 1-s2.0-S1935861X21001273-main_pub.pdf
Accepted Version - 1-s2.0-S1935861X21001273-main.pdf
Supplemental Material - 1-s2.0-S1935861X21001273-mmc1.docx
Files
Additional details
- Eprint ID
- 109660
- Resolver ID
- CaltechAUTHORS:20210629-215429809
- Ryan Family Fund for TMS Research
- Created
-
2021-07-01Created from EPrint's datestamp field
- Updated
-
2021-07-06Created from EPrint's last_modified field