Precision Closed-loop Brain-Computer Interface Neuromodulation for Treatment-Resistant Depression

The goal of this clinical trial is to evaluate whether precision closed‐loopneuromodulation treatments can improve depressive symptoms and daily functioning inpeople with treatment‐resistant major depressive disorder (TRD). The study will assessthe effectiveness and safety of two neuromodulation approaches: closed‐loop deep brainstimulation (DBS) and transcutaneous auricular vagus nerve stimulation (taVNS).Treatment‐resistant major depressive disorder refers to depression that does not improvesufficiently after adequate treatment with standard antidepressant therapies. This studyfocuses on people with TRD, including individuals with early‐onset depression, a historyof self‐harm or suicidal thoughts, or depression associated with traumatic experiences.This study aims to answer whether closed‐loop DBS and taVNS can reduce depressivesymptoms compared with sham stimulation, whether these treatments are safe and welltolerated, and whether changes in brain activity are associated with clinicalimprovement.This is a multicenter, prospective clinical study conducted at Shanghai Mental HealthCenter, Beijing Anding Hospital, and Xuanwu Hospital. Eligible participants with TRD willreceive either DBS or taVNS according to patient preference. Within each interventiongroup, participants will be randomly assigned to active stimulation or sham stimulationgroups to assess treatment effects.During the study, participants will receive neuromodulation treatment and completeregular follow‐up assessments. These assessments will include evaluation of depressivesymptoms, anxiety symptoms, cognitive function, social functioning, brain electricalactivity using electroencephalography (EEG), brain imaging using magnetic resonanceimaging (MRI), and monitoring of adverse events.The study will compare changes in clinical symptoms, brain‐related measures, and safetyoutcomes between active and sham stimulation groups. The findings may help determinewhether precision neuromodulation approaches can provide a new treatment option forpeople with treatment‐resistant major depressive disorder.