Antidepressant Efficacy of Prolonged Intermittent Theta Burst Stimulation Monotherapy for Recurrent Depression and Comparison of Methods for Coil Positioning: A Randomized, Double-Blind, Sham-Controlled Study

Background: Prolonged intermittent theta burst stimulation (piTBS) with triple doses of the standard protocol is an updated form of repetitive transcranial magnetic stimulation, and it is an effective add-on intervention for major depressive disorder. In the present study, our objective was to investigate the antidepressant efficacy of piTBS monotherapy. Efficacy between the standard 5-cm method and magnetic resonance imaging (MRI)–guided coil positioning to the left dorsolateral prefrontal cortex method was also compared. Methods: In the present double-blind, randomized, sham-controlled trial, 105 patients with recurrent depression who exhibited no responses to at least one adequate antidepressant treatment for the prevailing episode were assigned randomly to one of three groups: piTBS monotherapy (n = 35), repetitive transcranial magnetic stimulation monotherapy (n = 35), or sham stimulation (n = 35). The acute treatment period was 2 weeks. Half of the patients were randomized to MRI navigation in each group. Results: No serious adverse events were observed. The piTBS group exhibited significantly greater decreases in depression scores than the sham group at week 2 (−40.0% vs. −13.9%; p <.001 after correcting for multiple comparisons by Bonferroni [effect size (Cohen's d) = 1.12]), and the odds ratio for responses was high. The MRI navigation method (−32.4%) did not yield better antidepressant effects than the standard method (−40.6%). Brain stimulation and 17-item Hamilton Depression Rating Scale changes in the first week were the most important variables for predicting antidepressant responses. Conclusions: Left prefrontal piTBS monotherapy is effective for the treatment of recurrent depression, and the MRI-guided method of coil targeting is not better than the standard method.