Major depression occurs in about twenty-five percent of women and ten percent of men at some point in their lifetime. Non-response to antidepressant medication treatment is seen in up to 40% of individuals with major depression in clinical trials. In addition, medication use is often complicated by side effects such as confusion, unsteady gait, GI symptoms, cardiac arrhythmias, especially in the elderly. The main alternative to medication management for treatment resistant major depression is still Electroconvulsive Therapy (ECT). Although ECT is highly successful, with a 60-80% response rate in this treatment resistant population, its use is limited by cost, stigma, and minor adverse effects such as transient cardiovascular changes during treatment, confusion, or musculoskeletal soreness following the procedure. An alternative to ECT or medications has been developed, based on the ability to induce electrical currents within body tissue by magnetic stimulation. The procedure, called repetitive Transcranial Magnetic Stimulation (rTMS), is based on a similar mode of action to ECT, but provides subconvulsive levels of current to localized brain areas. Cortical stimulation has been used in Neurology/Neurophysiology for brain function mapping and epilepsy. Clinically, it has been applied experimentally to Parkinson's disease, multiple sclerosis, and depression. Between 1985 and 1997, 978 studies had been published on rTMS with about 57 patient studies on safety and efficacy in depression, demonstrating rTMS to be a safe and effective procedure. Additional reviews and studies published after 1997 reflect similar findings and work has led to initial guidelines for use from an International Workshop on rTMS. This study proposes to study rTMS as a safer alternative to ECT in three study groups of treatment resistant patients. Treatment parameters will be those established in the International Workshop on rTMS. The three study groups will include: (1) individuals who are treatment resistant depressed patients, who cannot tolerate ECT treatment due to adverse events with ECT, like memory complaints; (2) treatment resistant depressed patients with only partial improvement from ECT; and (3) treatment of resistant depressed patients who accept rTMS as an alternative to ECT.
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