Antidepressant effects of prolonged intermittent theta-burst stimulation monotherapy at the bilateral dorsomedial prefrontal cortex for medication and standard transcranial magnetic stimulation-resistant major depression: a three arm, randomized, double blind, sham-controlled pilot study

• Published in: European archives of psychiatry and clinical neuroscience Vol. 273; no. 7; pp. 1433 - 1442
• Main Authors: Cheng, Chih-Ming, Li, Cheng-Ta, Jeng, Jia-Shyun, Chang, Wen-Han, Lin, Wei-Chen, Chen, Mu-Hong, Bai, Ya-Mei, Tsai, Shih-Jen, Su, Tung-Ping
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2023; Springer; Springer Nature B.V
• Subjects: Analysis; Antidepressants; Clinical trials; Double-blind studies; Magnetic fields; Medicine; Medicine & Public Health; Mental depression; NCT; NCT04037592; Neurosciences; Original Paper; Prefrontal cortex; Psychiatry; Transcranial magnetic stimulation; Dorsomedial prefrontal cortex; Repetitive transcranial magnetic stimulation; Prolonged intermittent theta-burst stimulation; Treatment refractory depression; Anxiosomatic cluster symptoms
• ISSN: 0940-1334; 1433-8491
• DOI: 10.1007/s00406-022-01523-4

The dorsomedial prefrontal cortex (DMPFC) plays a pivotal role in depression and anxiosomatic symptom modulation. However, DMPFC stimulation using a double-cone coil has demonstrated inconsistent results for antidepressant efficacy. No study thus far has investigated the antidepressant and anti-anxiosomatic effects of prolonged intermittent theta-burst stimulation (piTBS) bilaterally over DMPFC. Furthermore, head-to-head comparisons of antidepressant effects between standard iTBS and piTBS warrant investigation. This double-blind, randomized, sham-controlled trial recruited 34 patients with highly treatment-resistant depression (TRD) unresponsive to antidepressants and standard repetitive transcranial magnetic stimulation (rTMS)/piTBS. These patients were randomly assigned to one of three monotherapy groups (standard iTBS, piTBS, or sham), with treatment administered bilaterally over the DMPFC twice per day for 3 weeks. The primary outcome was the overall changes of 17-item Hamilton Depression Rating Scale (HDRS-17) over 3-weeks intervention. The changes in Depression and Somatic Symptoms Scale (DSSS) as the secondary outcome and the anxiosomatic cluster symptoms as rated by HDRS-17 as the post-hoc outcome were measured. Multivariable generalized estimating equation analysis was performed. Although no differences in overall HDRS-17 changes between three groups were found, the antidepressant efficacy based on DSSS was higher in piTBS than in iTBS and sham at week 3 (group effect, p  = 0.003, post-hoc: piTBS > iTBS, p  = 0.002; piTBS > sham, p  = 0.038). In post-hoc analyses, piTBS had more alleviation in anxiosomatic symptoms than iTBS (group effect, p  = 0.002; post-hoc, p  = 0.001). This first randomized sham-controlled study directly compared piTBS and iTBS targeting the DMPFC using a figure-of-8 coil and found piTBS may fail to demonstrate a significant antidepressant effect on overall depressive symptoms, but piTBS seems superior in alleviating anxiosomatic symptoms, even in depressed patients with high treatment resistance. This Trial registration (Registration number: NCT04037592). URL: https://clinicaltrials.gov/ct2/show/NCT04037592 .