Objective: To replicate previous findings and to investigate related clinical factors of long-term benefits and safety of subcallosal cingulate gyrus deep brain stimulation (SCG-DBS) for treatment-resistant depression (TRD).

Methods: Sixteen patients with TRD (with either major depressive disorder or bipolar disorder, DSM-IV and DSM-5 criteria) receiving chronic SCG-DBS were followed for up to 11 years (January 2008 to June 2019). Demographic, clinical, and functioning data were collected pre-surgery and during the follow-up. Response was defined as a≥ 50% decrease from baseline in the 17-item Hamilton Depression Rating Scale (HAM-D 17) score, and remission was defined as≤ 7 in the HAM-D 17 score. The Illness Density Index (IDI) was used as a longitudinal measure of treatment effects. Survival analyses were performed for response outcomes and relapses.

Results: Depressive symptoms were significantly decreased over time (F= 2.37; P=. 04). Response and remission rates were 75% and 62.5% at individual endpoint. Based on Kaplan-Meier curve analysis, 55% of patients reached remission in 139 days. IDI curves showed sustained clinical improvements as measured with HAM-D 17 and Clinical Global Impression and sustained functioning improvement as measured with Global Assessment of Functioning scores. The procedure was generally safe and well tolerated (122 adverse events across 81 patient-years, of which 25 were related to SCG-DBS). Two patients committed suicide long after surgery.

Conclusions: SCG-DBS produced a robust and protracted improvement in most patients, which reinforces the possibility that SCG-DBS could be an alternative for patients with treatment-resistant unipolar or bipolar depression. Identification of clinical and neurobiological response predictors should guide the continuation of DBS for TRD, to obtain its indication soon.