THE EFFECTIVENESS OF repetitive transcranial magnetic stimulation (rTMS) and vagus nerve stimulation (VNS) in the treatment of refractory major depression has been demonstrated in several studies.[1-5] rTMS treatment includes the determination of the resting motor threshold (rMT), which defines treatment intensity and is based upon the excitability of the motor cortex. During treatment courses of several weeks, systematic changes in rMT have not been described.[2, 3] Based upon this combination therapy, we examined rMT in three male patients with therapy-resistant depression (mean age, 47.4 ± 6.8 years; Hospital Anxiety and Depression Scale, 20.5 ± 4.0; Cyberonics® model 102, Cyberonics, Houston, TX, USA; VNS parameters: 1.25 mA, 10 Hz, 30 s on time, 5 min off time). The patients gave informed consent to publish this letter. They were treated with VNS and rTMS trials of four sessions (rTMS parameters: 10 Hz; 80% motor threshold (MT); 1000 impulses in left dorsolateral prefrontal cortex stimulation). The patients were blinded to MT determination. During the first three rTMS treatment sessions, VNS was completely switched off for 10 min before and 10 min after treatment. During rTMS session 4, VNS was not switched off, and the rMT was measured during both the on and off modes. rMT was measured by holding the TMS coil over the hand area of the motor cortex. A twitch of the contralateral abductor pollicis brevis and first interosseous digitalis represented the intensity of rMT within the range of 0–100%. In all of the patients, rMT decreased during VNS-on stimulation conditions. As shown in recently published studies, however, rMT does not appear to be a static variable and changes in motor cortex excitability are implicated, similar to previous results.[3, 6, 7]

The present results suggest that VNS affects the motor cortex by increasing motor excitability, thereby reducing rMT. This reduction should be discussed as a significant indicator of increased responsiveness of the frontal and motor cortex due to VNS. When VNS and rTMS are given in combination, these effects seem to act synergistically, increasing the effectiveness of the treatment of major depression.

Future studies should evaluate the facilitation effect of VNS on rMT and focus on changes due to combined VNS–TMS treatment.


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  2. References
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    Gaynes BN, Lux LJ, Lloyd SW et al. Nonpharmacologic Interventions for Treatment-Resistant Depression in Adults, Report No.: 11-EHC056-EF. Agency for Healthcare Research and Quality (US), Rockville, MD; 2011.
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