Repetitive Transcranial Magnetic Stimulation

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Abstract
Transcranial magnetic stimulation (TMS) has become a major research tool in experimental clinical neurophysiology as a result of its potential to noninvasively and focally stimulate cortical brain regions. Currently, studies are being conducted to investigate whether repetitive TMS (rTMS)-mediated modulation of cortical function may also provide a therapeutic approach in neurological and psychiatric disorders. Preclinical findings have shown that prefrontal rTMS can modulate the function of fronto-limbic circuits, which is reversibly altered in major depression. rTMS has also been found to exert effects on neurotransmitter systems involved in the pathophysiology of major depression (e.g. stimulates subcortical dopamine release and acts on the hypothalamic pituitary adrenal axis, which is dysregulated in depression). To date, numerous open and controlled clinical trials with widely differing stimulation parameters have explored the antidepressant potential of rTMS. Though conducted with small sample sizes, the majority of the controlled trials demonstrated significant antidepressant effects of active rTMS compared with a sham condition. Effect sizes, however, varied from modest to substantial, and the patient selection focused on therapy-resistant cases. Moreover, the average treatment duration was approximately 2 weeks, which is short compared with other antidepressant interventions. Larger multicentre trials, which would be mandatory to demonstrate the antidepressant effectiveness of rTMS, have not been conducted to date. A putative future application of rTMS may be the treatment of patients who did not tolerate or did not respond to antidepressant pharmacotherapy before trying more invasive strategies such as electroconvulsive therapy and vagus nerve stimulation. Theoretically, rTMS may be also applied early in the course of disease in order to speed up and increase the effects of antidepressant pharmacotherapy. However, this application has not been a focus of clinical trials to date. Research efforts should be intensified to further investigate the effectiveness of rTMS as an antidepressant intervention and to test specific applications of the technique in the treatment of depressive episodes.

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