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. pmc The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial
    Jeffrey J Borckardt
    Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC, USA Electronic address
    Brain Stimul 6:925-8. 2013
  2. doi Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression
    Antonio Mantovani
    Department of Psychiatry, Columbia University College of Physicians and Surgeons New York State Psychiatric Institute, New York, New York 10032, USA
    Depress Anxiety 29:883-90. 2012
  3. pmc Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?
    Ashley B Arana
    Brain Stimulation Laboratory BSL, Psychiatry Department, Medical University of South Carolina MUSC, Charleston, SC 29425, USA
    Brain Stimul 1:44-51. 2008
  4. pmc The effect of daily prefrontal repetitive transcranial magnetic stimulation over several weeks on resting motor threshold
    Paul Zarkowski
    University of Washington, 325 Ninth Avenue, Seattle WA 98104 2499, USA
    Brain Stimul 2:163-7. 2009
  5. pmc Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial
    Kevin A Johnson
    Medical University of South Carolina, USA
    Brain Stimul 6:108-17. 2013
  6. doi Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression
    William M McDonald
    Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA
    Depress Anxiety 28:973-80. 2011
  7. doi Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial
    Mark S George
    Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA
    Arch Gen Psychiatry 67:507-16. 2010
  8. pmc Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS)
    Berry S Anderson
    Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, Charleston, SC 29425, USA
    Brain Stimul 2:88-92. 2009
  9. 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
  10. ncbi Known, forgotten and rediscovered--electricity and the brain
    Mark S George
    Clin EEG Neurosci 39:V-VII. 2008

Scientific Experts

Detail Information

Publications17

  1. pmc The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial
    Jeffrey J Borckardt
    Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA Department of Anesthesia and Perioperative Medicine, Medical University of South Carolina, Charleston, SC, USA Electronic address
    Brain Stimul 6:925-8. 2013
    ..The reduction in pain is hypothesized to be due to prefrontal stimulation and is not solely explained by accommodation to the stimulation...
  2. doi Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression
    Antonio Mantovani
    Department of Psychiatry, Columbia University College of Physicians and Surgeons New York State Psychiatric Institute, New York, New York 10032, USA
    Depress Anxiety 29:883-90. 2012
    ..This study examined the long-term durability of clinical benefit from TMS using a protocol-specified TMS taper and either continuation pharmacotherapy or naturalistic follow-up...
  3. pmc Focal electrical stimulation as a sham control for repetitive transcranial magnetic stimulation: Does it truly mimic the cutaneous sensation and pain of active prefrontal repetitive transcranial magnetic stimulation?
    Ashley B Arana
    Brain Stimulation Laboratory BSL, Psychiatry Department, Medical University of South Carolina MUSC, Charleston, SC 29425, USA
    Brain Stimul 1:44-51. 2008
    ....
  4. pmc The effect of daily prefrontal repetitive transcranial magnetic stimulation over several weeks on resting motor threshold
    Paul Zarkowski
    University of Washington, 325 Ninth Avenue, Seattle WA 98104 2499, USA
    Brain Stimul 2:163-7. 2009
    ..In many clinical studies to date, due to concerns about potential drift, the rMT has been routinely re-measured weekly or every fifth session...
  5. pmc Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial
    Kevin A Johnson
    Medical University of South Carolina, USA
    Brain Stimul 6:108-17. 2013
    ..However, anatomic variability results in variability of placement and effective intensity...
  6. doi Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression
    William M McDonald
    Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, USA
    Depress Anxiety 28:973-80. 2011
    ..And, to determine if patients who do not remit to fast left will remit using slow right rTMS (1 Hz @ 120% MT over the right DLPFC)...
  7. doi Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial
    Mark S George
    Brain Stimulation Division, Department of Psychiatry, Medical University of South Carolina, Charleston, SC 29425, USA
    Arch Gen Psychiatry 67:507-16. 2010
    ..Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions...
  8. pmc Decreasing procedural pain over time of left prefrontal rTMS for depression: initial results from the open-label phase of a multi-site trial (OPT-TMS)
    Berry S Anderson
    Brain Stimulation Laboratory, Psychiatry Department, Medical University of South Carolina, Charleston, SC 29425, USA
    Brain Stimul 2:88-92. 2009
    ..We analyzed interim results from the open-label phase of a multi-site randomized trial of rTMS as a treatment for depression to investigate whether the procedural pain of left prefrontal rTMS changes over time...
  9. 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...
  10. ncbi Known, forgotten and rediscovered--electricity and the brain
    Mark S George
    Clin EEG Neurosci 39:V-VII. 2008
  11. doi 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...
  12. 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
  13. pmc 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...
  14. 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...
  15. 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...