This resubmission 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, rTMS 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 rTMS stimulus administered may not have been of an adequate dose in terms of the intensity of stimulation or length of treatment in order to demonstrate an optimal 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 rTMS 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 5Hz rTMS 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 1Hz rTMS in an open trial over the right prefrontal cortex. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences 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 effect of TMS in remitters, using a standardized continuation medication protocol over 6 months. Finally, we will evaluate whether neuroanatomic findings on magnetic resonance images, stimulus location, demographic, and/or clinical variables affect clinical response to TMS. [This clinical site grant (CSG) proposal is one of four scientifically identical proposals resubmitted under a CSMD mechanism.]

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH069895-01A1
Application #
6823808
Study Section
Special Emphasis Panel (ZMH1-NRB-G (10))
Project Start
2004-09-15
Project End
2008-05-31
Budget Start
2004-09-15
Budget End
2005-05-31
Support Year
1
Fiscal Year
2004
Total Cost
$427,011
Indirect Cost
Name
New York State Psychiatric Institute
Department
Type
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
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
Stanford, Arielle D; Sharif, Zafar; Corcoran, Cheryl et al. (2008) rTMS strategies for the study and treatment of schizophrenia: a review. Int J Neuropsychopharmacol 11:563-76