Revisiting subcallosal cingulate deep brain stimulation for depression: Long-term safety and effectiveness outcomes from a pooled analysis of 172 implanted patients

OBJECTIVE: Deep brain stimulation (DBS) of the subcallosal cingulate (SCC) has been investigated clinically for treatment-resistant depression (TRD). Although the initial BROADEN study, a randomized controlled trial, was halted after an interim futility analysis, observation of long-term follow-up (LTFU) data from this and other cohorts demonstrated sustained improvement in depressive symptoms, prompting further investigation of DBS as a therapeutic option. METHODS: Data from 5 studies, including BROADEN, were used to evaluate the long-term safety and effectiveness of SCC DBS for TRD. Effectiveness measures included percent change in HDRS-17 and MADRS, response and partial response rate, and remission rate. Outcomes were assessed through five years post-implant, with primary analyses focused on the first 24 months due to attrition after this point. Sensitivity analyses were performed to evaluate robustness of the results, and adverse events were summarized. RESULTS: 172 subjects were implanted in 5 studies across 5 countries. Average age was 47.9 years, 8.1 years in the current depressive episode, and 88 % had received electroconvulsive therapy (ECT). Effectiveness outcomes were analyzed through 24 months; additional data through five years are available in the supplement. Average MADRS reduction was 43 % at 12 months and 53 % at 24 months post-device activation, with response rates of 46 % and 55 %, and partial response rates of 13.3 % and 15.5 %, respectively. Observed case and sensitivity analyses for both MADRS and HDRS-17 showed a significant reduction in depressive symptoms at each follow-up visit. Safety data from four studies included 151 implanted subjects with 523 patient-years. Incidence of suicide was 0.55 per 100 patient-years. CONCLUSIONS: Active SCC DBS shows continuous and sustained improvement in depressive symptomatology from the first year onward. While several limitations may impact the validity of these findings, SCC DBS has the possibility to provide a safe and durable treatment for TRD.