Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Unipolar and Bipolar Depression

Context: Deep brain stimulation (DBS) may be an effective intervention for treatment-resistant depression (TRD), but available data are limited. Objective: To assess the efficacy and safety of subcallosal cingulate DBS in patients with TRD with either major depressive disorder (MDD) or bipolar 11 disorder (BP). Design: Open-label trial with a sham lead-in phase. Setting: Academic medical center. Patients: Men and women aged 18 to 70 years with a moderate-to-severe major depressive episode after at least 4 adequate antidepressant treatments. Ten patients with MDD and 7 with BP were enrolled from a total of 323 patients screened. Intervention: Deep brain stimulation electrodes were implanted bilaterally in the subcallosal cingulate white matter. Patients received single-blind sham stimulation for 4 weeks followed by active stimulation for 24 weeks. Patients then entered a single-blind discontinuation phase; this phase was stopped after the first 3 patients because of ethical concerns. Patients were evaluated for up to 2 years after the onset of active stimulation. Main Outcome Measures: Change in depression severity and functioning over time, and response and remission rates after 24 weeks were the primary efficacy end points; secondary efficacy end points were 1 year and 2 years of active stimulation. Results: A significant decrease in depression and increase in function were associated with chronic stimulation. Remission and response were seen in 3 patients (18%) and 7 (41%) after 24 weeks (n=17), 5 (36%) and 5 (36%) after 1 year (n=14), and 7 (58%) and 11 (92%) after 2 years (n=12) of active stimulation. No patient achieving remission experienced a spontaneous relapse. Efficacy was similar for patients with MDD and those with BP. Chronic DBS was safe and well tolerated, and no hypomanic or manic episodes occurred. A modest sham stimulation effect was found, likely due to a decrease in depression after the surgical intervention but prior to entering the sham phase. Conclusions: The findings of this study support the long-term safety and antidepressant efficacy of subcallosal cingulate DBS for TRD and suggest equivalent safety and efficacy for TRD in patients with BP.