Yuki Matsuda

INTRODUCTION: The clinical efficacy of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) in Japan has not been adequately investigated. Furthermore, the relationship between stimulation-site pain and the antidepressant effects of rTMS has not been thoroughly examined. Therefore, this study aimed to clarify (1) the real-world efficacy and safety of rTMS for TRD in Japan and (2) the relationship between stimulation-site pain and clinical improvement of depressive symptoms. METHODS: We conducted a retrospective observational study involving 50 right-handed patients with TRD. All patients received high-frequency rTMS for up to 6 weeks. Depressive symptoms were assessed using the Montgomery-Åsberg depression rating scale (MADRS). Pain at the stimulation site was reported by the patients using a visual analog scale (VAS) after each session. Remission and response rates at 3 and 6 weeks were calculated based on the MADRS scores. The correlation between changes in the MADRS and VAS scores was examined. RESULTS: Remission and response rates were 36% and 46%, respectively, at the end of 3 weeks, and 60% and 70%, respectively, at 6 weeks. At the end of the treatment, there was significant correlation between the reduction of MADRS and VAS scores (r = 0.42, p = 0.003). CONCLUSION: This study demonstrates the clinical efficacy of rTMS in Japan and the correlation between its antidepressant effects and stimulation-site pain.

In clinical practice, theta burst stimulation (TBS) presents as a more efficient and potentially more effective therapeutic modality than conventional repetitive transcranial magnetic stimulation (rTMS), as it allows for the delivery of more stimuli in less time and at similar intensities. To date, accelerated treatment plans according to various continuous (cTBS) and intermittent TBS (iTBS) protocols for depression have been proposed. To investigate which of the TBS protocols provided a favorable risk-benefit balance for individuals with depression, this systematic review and random-effects model network meta-analysis was conducted. The study outcomes included response rate (primary), depression symptom improvement, remission rate, all-cause discontinuation rate, incidence of switch to mania, and incidence of headache/discomfort at treatment site. In this meta-analysis, a total of 23 randomized controlled trials (n = 960, mean age = 41.88 years, with 60.78% females) were included. Approximately 69.57% of the trials included individuals with an exclusive diagnosis of major depressive disorder. The following six TBS protocols (target) were evaluated: cTBS (right-dorsolateral prefrontal cortex [R-DLPFC]), cTBS (R-DLPFC) + iTBS (left-DLPFC [L-DLPFC]), iTBS (L-DLPFC), iTBS (L-DLPFC) + iTBS (R-DLPFC), iTBS (left-dorsomedial prefrontal cortex) + iTBS (right-dorsomedial prefrontal cortex), and iTBS (occipital lobe). Compared to sham, cTBS (R-DLPFC) + iTBS (L-DLPFC), iTBS (L-DLPFC), and iTBS (occipital lobe) had a higher response rate (k = 23); cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) dominated in the depression symptom improvement (k = 23); and iTBS (L-DLPFC) had a higher remission rate (k = 15). No significant differences were found for all-cause discontinuation rate (k = 17), incidence of switch to mania (k = 7), and incidence of headache/discomfort at treatment site (k = 10) between any TBS protocols and sham. Thus, cTBS (R-DLPFC) + iTBS (L-DLPFC) and iTBS (L-DLPFC) demonstrate favorable risk-benefit balance for the treatment of depression.