Repetitive Transcranial Magnetic Stimulation (Rtms) is a promising new treatment Major Depressive Disorder: some small controlled studies of high frequency rTMS electrical current is induced in the cortext of the brain by the magnetic field of a small electromagnetic coil placed on the scalp. Unlike electroconvulsive therapy (ETC), one of the most effective treatment for severe depression, rTMS gives a much smaller, subconvulsive stimulus and is more focal in its localization. Preliminary data suggest no disorientation, confusion, or memory disturbance associated with Rtms. We propose to study 86 drug-free patients with Major Depressive Disorder who have failed at least two trials of antidepressant medication either because of medication resistance and/or medication intolerance. The subjects will be randomized into one of two stimulations to the left DLPFC: 1) Rtms at 110 percent of motor threshold intensity at 10 Hz with 5 second trains (rTMS) or 2) Sham stimulation (the electromagnetic coil angled at 90 degrees so that the cortex is not stimulated) at 110 percent motor threshold intensity at 10 Hz for 5 seconds. Each subject will be given 10 sessions with 32 trains per session over a period of two weeks. Blind assessment of the depression will take place before the 1st Rtms session, after the 5th and 10th rTMS sessions and 1 week and 2 weeks after the 10 rTMS session. Neuropsychological measures fo attention, memory, language production, psychomotor speed, visual motor sequencing, cognitive flexibility, information processing speed and executive functioning will be administered by a trained examiner blind to treatment conditions at screening. Baseline, and following the last rTMS session. Additionally, measures of orientation, attention, and memory to monitor for post-rTMS confusion will be administered following each Rtms treatment session. We hypothesize that the rTMS stimulations will be significantly more efficacious than the sham stimulations. Ultimately, if Rtms is shown efficacious, safe and free from cognitive disturbance, rTMS could be an alternative treatment for depressed patients who have failed to respond to antidepressant medication trials. In a second phase of the study, we will place responders on maintenance antidepressant medication two weeks after the last rTMS session and evaluate them at follow-up visits 1 month, 2 month, 3 months, 4 months, 5 months, and 6 months after the last rTMS session. Nonresponders to sham stimulation will be offered rTMS.
