The goal of this clinical trial is to optimize the target brain areas for deep brain stimulation (DBS) for depression based on personalized brain imaging and stereo-electroencephalography（SEEG), to administer long-term DBS treatment in the target brain areas, to assess the effectiveness and safety of DBS for refractory depression and to validate the method of personalized optimization of DBS targets. The main questions it aims to answer are:
1. Where is the optimal DBS target brain region for each patient? 2. What are the optimal DBS parameters for each patient ? 3. What are the neural biomarkers of depression symptoms for each patient? 4. Are the optimized DBS strategies effective in treating refractory depression?
A psychiatrist-confirmed diagnosis of major depressive disorder in accordance with the Diagnostic And Statistical Manual Of Mental Disorders.5th Ed (DSM-V);
A psychiatric examination by two trained psychiatrists and a diagnosis consistent with the DSM-V;
A history of depression of at least 12 months duration in depressed patients (including MECT) who have failed to respond to a full dose and course of treatment with 2 or more antidepressants of different mechanisms;
A 17-item score on the HAMD scale ⩾ 20 at initial screening;
Persons with severe or unstable cardiac, hepatic, renal, endocrine, hematologic, and other medical disorders and co-morbidities with psychotic symptoms, including personality disorders diagnosed by history, questioning, and clinical examination;
Persons with psychiatric disorders other than depression (except generalized anxiety);
Persons with a history of substance abuse within 12 months; persons with a previous history of epilepsy, and persons with febrile convulsions in childhood;
Patients with a history of suicide attempts within the past 6 months or more than 2 suicide attempts within the past 2 years;
Single group
Deep Brain Stimulation(DBS)
DeviceDuring the DBS treatment phase, the DBS device will apply electrical stimulation to the patient's target brain regions using a specific strategy, and if the efficacy of this phase is not satisfactory, electrical stimulation will continue to be applied during the efficacy observation phase after DBS shutdown.
Esketamine
DrugSEEG intraoperative experiment: patients will be implanted with microelectrodes and connected to an electrophysiological recorder under local anesthesia. Intraoperative neurophysiological baseline will be recorded for 5 minutes, and esketamine will be injected intravenously at a dose of 0.5 mg/kg, and neurophysiological recordings will be continued for 15 minutes to observe the neuronal electrophysiological changes in various brain regions and target points.
Change in Hamilton Rating Scale for Depression (HAMD) score during the DBS treatment phase relative to preoperative baseline
Improvement is defined as a 25-49% reduction in Hamilton Rating Scale for Depression (HAMD) score relative to the preoperative baseline; response is defined as a ≥50% reduction in HAMD score relative to the preoperative baseline; and remission is defined as a HAMD score ≤8.
Changes in HAMD scores during the efficacy observation phase after DBS shutdown
Rebound is defined as a HAMD ≥18 in the subsequent follow-up period if the patient has an initial assessment of HAMD ≤8 in the efficacy observation phase after DBS shutdown, and rebound is defined as a HAMD score more than 2 times the initial assessment or 20 in the subsequent follow-up period if the patient has an initial assessment of HAMD \>8 in that phase.
the score of Montgomery-Asberg Depression Rating Scale (MADRS)
The score of the scale ranges from 0 to 60. Higher MADRS score indicates more severe depression.
the score of multi-lingual Hypomania Check List(C-SSRS)
The Multi-Lingual Hypomania Check List (C-SSRS) is a self-report questionnaire used to assess hypomanic symptoms and suicide risk. This tool includes multiple items designed to identify emotional and behavioral changes based on patient feedback. The results of the C-SSRS assist professionals in developing treatment plans, with higher scores typically indicating more severe symptoms, thereby facilitating timely intervention and support.
the score of Hamilton Anxiety Scale(HAMA)
The score of the scale ranges from 0 to 56. The higher scores means more severe anxiety.
the score of the Oxford Depression Questionnaire(ODQ)
The Oxford Depression Questionnaire (ODQ) is a self-report instrument designed to assess the presence and severity of depressive symptoms. It evaluates various aspects of mood, motivation, and behavior related to depression. The questionnaire consists of multiple items scored on a scale, where higher scores indicate greater levels of depressive symptoms, facilitating effective monitoring and intervention by healthcare professionals.
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