Safety and efficacy of individual target transcranial magnetic stimulation to stimulate the most negative correlate of DLPFC-pgACC in the treatment of major depressive disorder: study protocol of a double-blind, randomised controlled trial.

Abstract

Major depressive disorder (MDD) is a common mental disorder that is characterised by high morbidity, high rates of relapse, high rates of disability and, in severe cases, suicide ideas or even behaviour causing significant distress and burden. Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique widely used in the clinical treatment of MDD. Nevertheless, due to the imprecise selection and positioning of stimulation targets, their response rate is not as satisfactory. This trial was designed to treat MDD based on functional connectivity with individual target-TMS (IT-TMS) to stimulate the dorsolateral prefrontal cortex (DLPFC) where it correlates most negatively with the pregenual anterior cingulate cortex (pgACC). We will validate the safety and efficacy of IT-TMS for MDD using pgACC as an effector target, analyse the underlying antidepressant mechanism of the DLPFC-ACC brain network and search for neuroimaging markers that predict the efficacy of TMS. This is a single-centre, randomised, double-blind and sham-stimulation-controlled clinical trial. We aim to recruit approximately 68 depressed patients with MDD aged 18-60 years. Eligible participants will be randomised into the DLPFC-pgACC localisation and sham stimulation groups. The IT-TMS treatment will last 10 days and will be combined with antidepressant medication. Assessments will be confirmed at baseline, on day 5 of treatment and at the end of treatment with follow-up at weeks 2, 4 and 8 after the end of treatment. The primary outcome measure is the difference in the Hamilton Depression Scale score between baseline and end of treatment. The Ethics Committee of the First Affiliated Hospital of the Air Force Medical University has approved this clinical trial (project code: XJLL-KY20222111). The trial's results will be published in international peer-reviewed journals and presented at academic conferences. ClinicalTrials.gov PRS (ID: NCT05577481).