A sequential dual-site repetitive transcranial magnetic stimulation for major depressive disorder: A randomized clinical trial

Repetitive transcranial magnetic stimulation (rTMS) is approved for major depressive disorder (MDD), but it is limited by variable efficacy. Here, we examine antidepressant effects of our sequential dorsolateral prefrontal cortex (dlPFC)-dorsomedial prefrontal cortex (dmPFC) accelerated rTMS protocol, which includes a 4-day treatment with 4 sessions per day. At week 4, the Montgomery-Åsberg Depression Rating Scale (MADRS) reduction is significantly larger in the active group, and critical, significant differences were apparent on day 4. For active and sham-controlled groups, respectively, response rates are 57.69% and 23.08%, and remission rates are 38.46% and 15.38%. Of responders, over 85% remain in remission over 6 months. Resting-state fMRI shows dissociable symptom improvement associated with increased dlPFC-frontoparietal and decreased dmPFC-amygdalo-subcallosal cingulate functional connectivity. We highlight a cost-efficient generalizable rTMS approach targeting differential networks in MDD, which shows rapid and sustained antidepressant effects with a relatively small number of pulses and minimal treatment duration. The study is registered with ChiCTR (ChiCTR2100046042).