This study will investigate the safety and efficacy of deep brain stimulation (DBS) in lateral habenula (LH) for patients with treatment-resistant depression.

Inclusion Criteria:

1. Age 18-70, regardless of gender;
2. Diagnostic And Statistical Manual Of Mental Disorders 5th Ed (DSM-V), for Psychiatrists' Examination of Severe Depressive Disorders;
3. Same diagnostic conclusions based on DSM-V made by two independent psychiatrists;
4. A minimum of 24 months of depressive history, over 2 or more adequate antidepressant trials with Hamilton Depression Rating Scale (HAMD) reduction rate ≤20% (including MECT) ;
5. HAMD-17 scores ⩾ 20 at screening;
6. Functional General Assessment Table (GAF) rating ≤50;
7. Able to comply with the operational and administrative requirements of participation in the study, and able to give written informed consent.

Exclusion Criteria:

1. Patients with severe or unstable mental, liver, kidney, endocrine, hematological diseases, or those with psychotic co-morbidities, including personality disorders;
2. History of substance abuse in the past 12 months; history of epilepsy, or febrile seizure in childhood;
3. Patients who have attempted suicide within the past 6 months, or have had a secondary suicide attempt within the past 2 years;
4. Women who are breastfeeding, pregnant, or intend to be pregnant during the clinical study;
5. Any surgical contraindications to undergoing deep brain stimulation (DBS);
6. Patients who cannot give full informed consent.