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Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers

Corlier, Juliana and Tadayonnejad, Reza and Wilson, Andrew C. and Lee, Jonathan C. and Marder, Katharine G. and Ginder, Nathaniel D. and Wilke, Scott A. and Levitt, Jennifer and Krantz, David and Leuchter, Andrew F. (2021) Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers. Psychological Medicine . ISSN 0033-2917. doi:10.1017/S0033291721002178. (In Press)

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Background: Major depressive disorder (MDD) and chronic pain are highly comorbid, and pain symptoms are associated with a poorer response to antidepressant medication treatment. It is unclear whether comorbid pain also is associated with a poorer response to treatment with repetitive transcranial magnetic stimulation (rTMS). Methods: 162 MDD subjects received 30 sessions of 10 Hz rTMS treatment administered to the left dorsolateral prefrontal cortex (DLPFC) with depression and pain symptoms measured before and after treatment. For a subset of 96 patients, a resting-state electroencephalogram (EEG) was recorded at baseline. Clinical outcome was compared between subjects with and without comorbid pain, and the relationships among outcome, pain severity, individual peak alpha frequency (PAF), and PAF phase-coherence in the EEG were examined. Results: 64.8% of all subjects reported pain, and both depressive and pain symptoms were significantly reduced after rTMS treatment, irrespective of age or gender. Patients with severe pain were 27% less likely to respond to MDD treatment than pain-free individuals. PAF was positively associated with pain severity. PAF phase-coherence in the somatosensory and default mode networks was significantly lower for MDD subjects with pain who failed to respond to MDD treatment. Conclusions: Pain symptoms improved after rTMS to left DLPFC in MDD irrespective of age or gender, although the presence of chronic pain symptoms reduced the likelihood of treatment response. Individual PAF and baseline phase-coherence in the sensorimotor and midline regions may represent predictors of rTMS treatment outcome in comorbid pain and MDD.

Item Type:Article
Related URLs:
URLURL TypeDescription
Corlier, Juliana0000-0002-1342-5505
Lee, Jonathan C.0000-0003-3934-6458
Marder, Katharine G.0000-0002-3073-2427
Ginder, Nathaniel D.0000-0003-1854-2337
Wilke, Scott A.0000-0002-7421-4015
Krantz, David0000-0002-4208-1633
Additional Information:© The Author(s), 2021. Published by Cambridge University Press. This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, which permits unrestricted re- use, distribution and reproduction, provided the original article is properly cited. Received: 28 August 2020; Revised: 16 April 2021; Accepted: 13 May 2021. Published online by Cambridge University Press: 22 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. Dr Corlier was supported by the Neuromodulation Postdoctoral Scholar Fund, which was established by the generous gifts of Janet and Barry Lang, Sally and David Weil, and in memory of Morris A. Hazan. Their contributions have advanced the university's education and research missions through the support of a postdoctoral scholar in the Neuromodulation Division. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Conflict of interest: Drs Corlier, Tadayonnejad, Marder, Ginder, Wilke, Levitt, and Krantz have no disclosures. Wilson has served as a consultant to HeartCloud, Inc. within the past 36 months. Dr Lee has received equipment in-kind support from Magventure Inc. Dr Leuchter discloses that within the past 36 months he has received research support from the National Institutes of Health, 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 an equity interest in BBA.
Subject Keywords:Major depressive disorder (MDD); Chronic Pain; Repetitive transcranial magnetic stimulation (rTMS); peak alpha frequency (PAF); phase coherence
Record Number:CaltechAUTHORS:20210716-212219116
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Official Citation:Corlier J et al (2021). Repetitive transcranial magnetic stimulation treatment of major depressive disorder and comorbid chronic pain: response rates and neurophysiologic biomarkers. Psychological Medicine 1–10.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109885
Deposited By: Tony Diaz
Deposited On:16 Jul 2021 21:47
Last Modified:16 Jul 2021 21:47

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