Safety and efficacy of individualized target transcranial magnetic stimulation for major depressive disorder based on DLPFC-pgACC functional connectivity: a randomized, sham-controlled clinical trial

Major Depressive Disorder (MDD) has emerged as a major global public health challenge. Recently, Stanford neuromodulation therapy, a paradigm of individualized target-transcranial magnetic stimulation (IT-TMS) focusing on the subgenual anterior cingulate cortex (sgACC), has exhibited significant therapeutic benefits in treating MDD. The pregenual anterior cingulate cortex (pgACC), alongside the sgACC, is also an emotional subregion of the anterior cingulate cortex (ACC). This study aims to explore the safety and efficacy of IT-TMS targeting the pgACC for the treatment of MDD. This is a randomized, double-blind, sham-controlled trial involving 68 patients with MDD randomly assigned to an IT-TMS group and a sham group. The IT-TMS group receives individualized intermittent theta-burst stimulation targeted at the region in the left dorsolateral prefrontal cortex (DLPFC) with the strongest negative functional connectivity to the pgACC. The sham group undergoes a well-accepted 90 ° -reversed sham stimulation procedure. The primary outcome is the percentage change in the 17-item Hamilton Rating Scale for Depression (HAMD-17) score from baseline to the end of treatment. In the final intention-to-treat analysis, 31 participants from the IT-TMS group and 34 from the sham group were included. From baseline to the end of IT-TMS treatment, the mean percentage reduction in HAMD-17 score was 64.3% (95% CI: 55.9–72.7) for the IT-TMS group versus 41.4% (95% CI: 33.9–48.8) for the sham group, yielding a significant treatment effect ( P = 0.0001). This IT-TMS therapy has demonstrated good safety and effectiveness in the treatment of MDD, with the ability to rapidly alleviate related symptoms in patients. This study was registered on the ClinicalTrials.gov (NCT05577481).