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.