The Effectiveness of rTMS in Depressed VA Patients

Major depression occurs in about 10% of American outpatients every year and of those, approximately 20% respond incompletely or not at all to trials of antidepressants, mood stabilizers, or psychotherapy (Kaplan and Sadock, 1996; Keller et al 1992; Thase, 2004). Treatment as usual for these cases of treatment resistant major depression (TRMD) frequently involves increased risks and increased side effects, such as those seen in monoamine oxidase inhibitors (MAOIs) and electroconvulsive therapy (ECT). New TRMD treatments are needed, preferably without major safety concerns or side effects as seen with aggressive polypharmacy or ECT. Repetitive transcranial magnetic stimulation (rTMS) is a method of delivering brain stimulation without the seizures or risks associated with ECT, nor the potential side effects and risks of MAOI therapy. Systematic review and meta-analysis of the studies to date, which are typically of a small scale, appear to show a positive effect in TRMD (Martin et al. 2003). With a minimal side effect profile, and the rarity of untoward events and side-effects (Pascual-Leone et al. 1993; Wassermann 1997), safety concerns regarding the use of rTMS are considerably less than with ECT. Given this, rTMS has the potential to be a significant advance in care, if it were shown to be effective in TRMD in VA patients. The trials of rTMS performed to date have not included participants with comorbid disorders, such as substance abuse and post-traumatic stress disorder (PTSD), thus the generalizability of their findings to a VA population is not clear. Further research including Veterans with possible comorbid disorders is necessary, given the high rates of co-occurring substance abuse and PTSD that is present in the Veteran population. The present study is a randomized, controlled trial that compares active rTMS to a sham condition in Veterans with treatment resistant major depression and possible comorbid post-traumatic stress disorder (PTSD) and / or a history of substance abuse. Veterans will remain under the care of their VA primary mental health provider throughout the project. Participants will be assessed at pre-, mid- and several post-treatment time points. This is a multisite trial that will be conducted at 9 VA Medical Centers around the country.