Abstract

<h3>Background</h3> High-frequency left-sided repetitive transcranial magnetic stimulation (HFL-TMS) has been shown to have antidepressant effects in double-blind trials. Low-frequency stimulation to the right prefrontal cortex (LFR-TMS) has also shown promise, although it has not been assessed in treatment-resistant depression and its effects have not been compared with those of HFL-TMS. <h3>Objective</h3> To prospectively evaluate the efficacy of HFL-TMS and LFR-TMS in treatment-resistant depression and compared with a sham-treated control group. <h3>Design</h3> A double-blind, randomized, sham-controlled trial. <h3>Setting</h3> Two general psychiatric services. <h3>Participants</h3> Sixty patients with treatment-resistant depression who had failed to respond to therapy with multiple antidepressant medications were divided into 3 groups of 20 that did not differ in age, sex, or any clinical variables. All patients completed the double-blind phase of the study. <h3>Interventions</h3> Twenty 5-second HFL-TMS trains at 10 Hz and five 60-second LFR-TMS trains at 1 Hz were applied daily. Sham stimulation was applied with the coil angled at 45° from the scalp, resting on the side of one wing of the coil. <h3>Main Outcome Measure</h3> Score on the Montgomery-Åsberg Depression Rating Scale. <h3>Results</h3> There was a significant difference in response among the 3 groups (F<sub>56,2</sub>= 6.2), with a significant difference between the HFL-TMS and sham groups and between the LFR-TMS and sham groups (<i>P</i>&lt;.005 for all) but not between the 2 treatment groups. Baseline psychomotor agitation predicted successful response to treatment. <h3>Conclusions</h3> Both HFL-TMS and LFR-TMS have treatment efficacy in patients with medication-resistant major depression. Treatment for at least 4 weeks is necessary for clinically meaningful benefits to be achieved. Treatment with LFR-TMS may prove to be an appropriate initial repetitive TMS strategy in depression taking into account safety, tolerability, and efficacy considerations.

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