Therapeutic Application of Repetitive Transcranial Magnetic Stimulation for Major Depression
Laboratory of neuromodulation, Kinkou Hospital, Kanagawa Psychiatric Center
Department of Psychiatry, Yokohama City University School of Medicine
Department of Psychiatry, Showa University School of Medicine
Psychiatria et Neurologia Japonica 114: 1231-1249, 2012

 It has been reported that approximately one third of patients with major depression are medication-resistant. In spite of partial responsiveness to antidepressants, most of the medication-resistant patients remain incompletely remitted without successful social reintegration. Symptom severity could be mild to moderate for many of them due to the incomplete remission, and, thus, electroconvulsive therapy is not applicable for them. However, they usually feel some difficulty performing cognitive behavioral therapy or social rehabilitation training due to residual symptoms such as thought inhibition and hypobulia. Under such conditions, those patients are longing for treatment options complementary to antidepressants, for less painful social reintegration.In October 2008,the Food and Drug Administration (FDA)of the United States finally approved repetitive Transcranial Magnetic Stimulation(rTMS)for medication-resistant patients with major depression. The main reason for the FDA approval was that rTMS had shown similar effectiveness(effect size around 0.39 in a recent meta-analysis)to antidepressants for medication-resistant patients without serious adverse effects. TMS is a brain stimulation methodology employing magnetic energy which can penetrate the skull bone without energy decay,and,thus,eddy currents induced by TMS can stimulate cerebral cortices effectively and locally. When TMS is repetitively delivered over several hundreds of pulses within a session, stimulation effects can be observed beyond the stimulation period as aftereffects.Moreover,when a daily rTMS session is repeated over several weeks, rTMS could have antidepressant effects. Clinical trials of rTMS for depression have employed two kinds of rTMS protocol of high-frequency(facilitatory)rTMS over the left Dorsolateral Prefrontal Cortex(DLPFC)and low-frequency(inhibitory)rTMS over the right DLPFC. Although the antidepressant action of rTMS over DLPFC has not been fully elucidated, the neuronal level hypothesis includes the induction of neuroplasticity and activation of the dopamine system, and the neuronal circuitry level hypothesis includes the activation of the left DLPFC and inhibition of the right DLPFC and(para)limbic system such as the subgenual cingulate cortex and amygdala. On the therapeutic application of rTMS in clinical psychiatry, neuroethics and low invasiveness should be fully considered along with a negative history of punitive electroconvulsive therapy and prefrontal lobotomy. It is important to investigate the neurobiological mechanism of rTMS treatment and to place rTMS in a suitable position within comprehensive treatment algorithms of major depression.

Keywords:repetitive transcranial magnetic stimulation(rTMS), major depression, dorsolateral prefrontal cortex(DLPFC), neuroplasticity, neuromodulatio>


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