Optimization of TMS for Depression - Coordinating Center

Summary

Principal Investigator: Mark George
Affiliation: Medical University of South Carolina
Country: USA
Abstract: This application requests support for a 4 year, 4 site randomized sham-controlled trial of daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) for the acute treatment of major depression. TMS has shown an antidepressant effect in 20 small sample randomized controlled comparisons, five separate meta-analyses of these studies, and in randomized trials with electroconvulsive therapy. However, the sample sizes of these studies have been small and the TMS stimulus administered may not have been optimal for antidepressant effect. Considerable skepticism and many questions remain concerning the ultimate clinical meaningfulness of these studies. Recent scientific evidence and pilot data from our groups support the fact that the antidepressant response to rTMS is dose-dependent. The present protocol uses TMS parameters that maximize the stimulation duration and intensity within the published safety guidelines to treat 240 unipolar depressed adults with moderate levels of treatment resistance. We will investigate the safety and efficacy of repeated daily left prefrontal TMS at 120% of motor threshold (MT) in a 3 week fixed dose trial. In subjects showing an antidepressant response after 3 weeks, rTMS will be administered for up to 6 weeks to achieve remission of clinical symptoms of depression. Patients who do not remit with the initial fixed dose trial will be administered rTMS in an open dose escalation trial with the intensity of rTMS increased to a maximum of 140% MT. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual variations in cortical to skull distances. Safety measures will include the most comprehensive neuropsychological testing and adverse event profile used to date. We will also determine the long-term antidepressant affect of TMS in remitters, using a standardized continuation medication protocol over 6 months. Finally, we will evaluate whether neuroanatomic findings on magnetic resonance image, stimulus location, demographic, and/or clinical variables affect clinical response to TMS. (This coordinating Center Grant (CCG) application is submitted under a CSMD mechanism, linked to 4 clinical site grants (CSG).
Funding Period: 2004-09-29 - 2010-05-31
more information: NIH RePORT

Top Publications

  1. ncbi Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young men
    Berry Anderson
    Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, 29425, USA
    J ECT 22:49-53. 2006
  2. ncbi Deep brain stimulation in movement and psychiatric disorders
    David E Hardesty
    Department of Biological Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA
    Biol Psychiatry 61:831-5. 2007
  3. ncbi Transcranial magnetic stimulation: a stimulating new method for treating depression, but saddled with the same old problems
    Mark S George
    Medical University of South Carolina, Charleston, SC 29425, USA
    Int J Neuropsychopharmacol 9:637-40. 2006
  4. ncbi Known, forgotten and rediscovered--electricity and the brain
    Mark S George
    Clin EEG Neurosci 39:V-VII. 2008
  5. ncbi Prefrontal EEG asymmetry as a potential biomarker of antidepressant treatment response with transcranial magnetic stimulation (TMS): a case series
    Agnes P Funk
    Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina MUSC, Charleston, South Carolina, USA
    Clin EEG Neurosci 39:125-30. 2008
  6. ncbi Focal electrically administered therapy: device parameter effects on stimulus perception in humans
    Jeffrey J Borckardt
    Psychiatry Department, Medical University of South Carolina, Charleston, SC 29425, USA
    J ECT 25:91-8. 2009
  7. ncbi More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response
    Tal Herbsman
    Department of Psychiatry, Brain Stimulation Laboratory, Center for Advanced Imaging Research, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Biol Psychiatry 66:509-15. 2009

Scientific Experts

Detail Information

Publications8

  1. ncbi Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young men
    Berry Anderson
    Brain Stimulation Laboratory, Department of Psychiatry, Medical University of South Carolina, Charleston, 29425, USA
    J ECT 22:49-53. 2006
    ..Despite this intense treatment regimen, we failed to produce significant side effects. Doses of up to 12,960 pulses per day appear safe and tolerable in healthy young men...
  2. ncbi Deep brain stimulation in movement and psychiatric disorders
    David E Hardesty
    Department of Biological Psychiatry, New York State Psychiatric Institute, New York, New York 10032, USA
    Biol Psychiatry 61:831-5. 2007
    ..Deep brain stimulation may prove to be a reasonable option for severely ill and treatment-resistant patients who otherwise have limited therapeutic options and a poor prognosis...
  3. ncbi Transcranial magnetic stimulation: a stimulating new method for treating depression, but saddled with the same old problems
    Mark S George
    Medical University of South Carolina, Charleston, SC 29425, USA
    Int J Neuropsychopharmacol 9:637-40. 2006
  4. ncbi Known, forgotten and rediscovered--electricity and the brain
    Mark S George
    Clin EEG Neurosci 39:V-VII. 2008
  5. ncbi Prefrontal EEG asymmetry as a potential biomarker of antidepressant treatment response with transcranial magnetic stimulation (TMS): a case series
    Agnes P Funk
    Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina MUSC, Charleston, South Carolina, USA
    Clin EEG Neurosci 39:125-30. 2008
    ..EEG shows potential as a biomarker of response for depression treatments, particularly the brain stimulation devices, which, unlike medications, can focally interact with neural tissue in specific frequency patterns...
  6. ncbi Focal electrically administered therapy: device parameter effects on stimulus perception in humans
    Jeffrey J Borckardt
    Psychiatry Department, Medical University of South Carolina, Charleston, SC 29425, USA
    J ECT 25:91-8. 2009
    ..This study used a simpler paradigm and evaluated the effects of different stimulation parameters on subjective perception of the quality and location of scalp pain...
  7. ncbi More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response
    Tal Herbsman
    Department of Psychiatry, Brain Stimulation Laboratory, Center for Advanced Imaging Research, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    Biol Psychiatry 66:509-15. 2009
    ..This study is a post hoc analysis of data from a large repetitive TMS (rTMS) trial in which we examined the variability of coil placement and how it affects antidepressant efficacy...