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Author Notes:

Kevin A. Johnson, Ph.D., RN, Stanford Systems Neuroscience & Pain Laboratory, 780 Welch Road #208, Palo Alto, CA 94304, johnsk@stanford.edu.

Following a competitive bid and request involving all TMS manufacturers at the time of trial initiation, Neuronetics Inc was selected and loaned the TMS devices, head holders, and coils for the trial and allowed use of the safety Investigational Device Exemption for their device.

The authors wish to acknowledge the many individuals involved in the OPT-TMS Study, who are listed in the primary clinical report:

Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA Arch Gen Psychiatry. 2010 May; 67(5):507-16.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.

See publication for full list of disclosures.


Research Funding:

This study was supported by the National Institute of Mental Health as the Optimization of TMS for the Treatment of Depression Study (OPT-TMS) involving grants 5R01MH069929 (Dr Avery), 5R01MH069887 (Dr George), 5R01MH069896 (Dr. George), 5R01MH069895 (Dr Lisanby), and 5R01MH069886 (Dr McDonald).


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences
  • Neurosciences & Neurology
  • Transcranial magnetic stimulation (TMS)
  • Imaging (MRI)
  • Motor cortex
  • Prefrontal cortex
  • Depression
  • Classifications
  • Transcranial Magnetic Stimulation (TMS)
  • Psychiatry

Prefrontal rTMS for Treating Depression: Location and Intensity Results from the OPT-TMS Multi-Site Clinical Trial

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Journal Title:

Brain Stimulation


Volume 6, Number 2


, Pages 108-117

Type of Work:

Article | Post-print: After Peer Review


Background: Motor cortex localization and motor threshold determination often guide Transcranial Magnetic Stimulation (TMS) placement and intensity settings for non-motor brain stimulation. However, anatomic variability results in variability of placement and effective intensity. Objective: Post-study analysis of the OPT-TMS Study reviewed both the final positioning and the effective intensity of stimulation (accounting for relative prefrontal scalp-cortex distances). Methods: We acquired MRI scans of 185 patients in a multi-site trial of left prefrontal TMS for depression. Scans had marked motor sites (localized with TMS) and marked prefrontal sites (5 cm anterior of motor cortex by the "5 cm rule"). Based on a visual determination made before the first treatment, TMS therapy occurred either at the 5 cm location or was adjusted 1 cm forward. Stimulation intensity was 120% of resting motor threshold. Results: The "5 cm rule" would have placed stimulation in premotor cortex for 9% of patients, which was reduced to 4% with adjustments. We did not find a statistically significant effect of positioning on remission, but no patients with premotor stimulation achieved remission (0/7). Effective stimulation ranged from 93 to 156% of motor threshold, and no seizures were induced across this range. Patients experienced remission with effective stimulation intensity ranging from 93 to 146% of motor threshold, and we did not find a significant effect of effective intensity on remission. Conclusions: Our data indicates that individualized positioning methods are useful to reduce variability in placement. Stimulation at 120% of motor threshold, unadjusted for scalp-cortex distances, appears safe for a broad range of patients.

Copyright information:

© 2013 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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