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). ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH069887-04
Application #
7250236
Study Section
Special Emphasis Panel (ZMH1-NRB-G (17))
Program Officer
Hillefors, MI
Project Start
2004-09-29
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2010-05-31
Support Year
4
Fiscal Year
2007
Total Cost
$564,943
Indirect Cost
Name
Medical University of South Carolina
Department
Psychiatry
Type
Schools of Medicine
DUNS #
183710748
City
Charleston
State
SC
Country
United States
Zip Code
29425
Johnson, Kevin A; Baig, Mirza; Ramsey, Dave et al. (2013) Prefrontal rTMS for treating depression: location and intensity results from the OPT-TMS multi-site clinical trial. Brain Stimul 6:108-17
Borckardt, Jeffrey J; Nahas, Ziad H; Teal, John et al. (2013) 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. Brain Stimul 6:925-8
Mantovani, Antonio; Pavlicova, Martina; Avery, David et al. (2012) Long-term efficacy of repeated daily prefrontal transcranial magnetic stimulation (TMS) in treatment-resistant depression. Depress Anxiety 29:883-90
McDonald, William M; Durkalski, Valerie; Ball, Edward R et al. (2011) Improving the antidepressant efficacy of transcranial magnetic stimulation: maximizing the number of stimulations and treatment location in treatment-resistant depression. Depress Anxiety 28:973-80
George, Mark S; Lisanby, Sarah H; Avery, David et al. (2010) Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry 67:507-16
Anderson, Berry S; Kavanagh, Katie; Borckardt, Jeffrey J et al. (2009) 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). Brain Stimul 2:88-92
Borckardt, Jeffrey J; Linder, Katherine J; Ricci, Raffaella et al. (2009) Focal electrically administered therapy: device parameter effects on stimulus perception in humans. J ECT 25:91-8
Zarkowski, Paul; Navarro, Rita; Pavlicova, Martina et al. (2009) The effect of daily prefrontal repetitive transcranial magnetic stimulation over several weeks on resting motor threshold. Brain Stimul 2:163-7
Herbsman, Tal; Avery, David; Ramsey, Dave et al. (2009) More lateral and anterior prefrontal coil location is associated with better repetitive transcranial magnetic stimulation antidepressant response. Biol Psychiatry 66:509-15
George, Mark S; Sackeim, Harold A (2008) Brain stimulation, revolutions, and the shifting time domain of depression. Biol Psychiatry 64:447-8

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