Optimization of TMS for Depression - Coordinating Center
Principal Investigator: Mark George
Affiliation: Medical University of South Carolina
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
- The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS TrialJeffrey 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...
- Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depressionAntonio 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...
- 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....
- The effect of daily prefrontal repetitive transcranial magnetic stimulation over several weeks on resting motor thresholdPaul 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...
- Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trialKevin 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...
- Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depressionWilliam 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)...
- Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trialMark 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...
- 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...
- Deep brain stimulation in movement and psychiatric disordersDavid 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...
- Known, forgotten and rediscovered--electricity and the brainMark S George
Clin EEG Neurosci 39:V-VII. 2008
- More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant responseTal 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...
- Transcranial magnetic stimulation: a stimulating new method for treating depression, but saddled with the same old problemsMark S George
Medical University of South Carolina, Charleston, SC 29425, USA
Int J Neuropsychopharmacol 9:637-40. 2006
- Focal electrically administered therapy: device parameter effects on stimulus perception in humansJeffrey 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...
- Prefrontal EEG asymmetry as a potential biomarker of antidepressant treatment response with transcranial magnetic stimulation (TMS): a case seriesAgnes 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...
- Tolerability and safety of high daily doses of repetitive transcranial magnetic stimulation in healthy young menBerry 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...