Effects of High-Frequency Repetitive Transcranial Magnetic Stimulation on the Treatment-Resistant Depression and Its Mechanism

Transcranial magnetic stimulation (TMS) is a technique for noninvasively and almost painlessly stimulating the central nervous system. Following the development of repetitive TMS (rTMS), many studies about the antidepressant effect of rTMS have been performed and it has now been licensed in many countries for the treatment of depression. Nevertheless, it has not been completely confirmed that rTMS is conclusively effective in treating depression. This might be the reason why it has not yet become common tool for the treatment of depressive disorder in Japan. In the present study, we performed clinical trials of high-frequency rTMS (20 Hz) for the treatment of treatment-resistant depression. We also measured plasma levels of catecholamine metabolites and brain-derived neurotrophic factor (BDNF) to clarify the mechanism of the action of rTMS in the treatment of depression. Twenty-six depressed patients who met the DSM-IV criteria for major depressive disorder participated in this study. Eleven were male, 15 female. The ages of the subjects ranged from 19 to 78 years old (meanplusmnSD=52.9plusmn17.8). All patients were given left prefrontal 20 Hz rTMS at 80% MT (total 800 pulses a day) over ten daily sessions. The mean 17-item Hamilton rating scale for depression (Ham-D) score of 20.5plusmn5.2 before rTMS decreased significantly to 15.6plusmn7.3 after rTMS. Nine of 26 patients demonstrated some improvement (Ham-Dges25%) after rTMS. The levels of plasma MHPG were significantly reduced after rTMS treatment, and it was observed that the change in plasma MHPG levels had a negative correlation with the change in scores of agitation. Furthermore the plasma levels of BDNF were significantly increased in responders and partial responders, but not in nonresponders, after rTMS treatment. These results suggest that rTMS treatment brings about some improvement in refractory depression, especially in depression with symptoms such as agitation. rTMS might have an antidepressant acti- - on by altering MHPG and BDNF levels in the central nervous system.