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

Abstract

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 II 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.

Long-Term Effects of Nucleus Accumbens Deep Brain Stimulation in Treatment-Resistant Depression: Evidence for Sustained Efficacy

“…Owing to symptom aggravation and delayed recurrence as well as weaker antidepressant effect, the design was changed leaving out the sham condition. These problems have been reported also by Holtzheimer et al (2012) during a single-blind discontinuation phase in therapy-resistant depression and by Denys et al (2010) in patients suffering from obsessive-compulsive disorder. This is a strong limitation in respect to placebo effects.…”

Modulation of brain response to emotional conflict as a function of current mood in bipolar disorder: Preliminary findings from a follow-up state-based fMRI study

“…A central involvement of the rostral ACC in the pathophysiology of both unipolar and bipolar mood disorders has been documented (e.g. Holtzheimer et al, 2012;Emsell et al, 2014). The rostral ACC overlaps with the default-mode network (DMN), which is typically active during the resting state (Qin and Northoff, 2011), and its hyperactivity at rest may reflect excessive self-referential processing (Lemogne et al, 2012).…”

Neurostimulation as an intervention for treatment resistant depression: From research on mechanisms towards targeted neurocognitive strategies

“…Recent years have witnessed more targeted applications of neurostimulation to regions that have been implicated in disrupted emotion processing known to be involved in TRD, such as the subgenual cingulate cortex (Ressler & Mayberg, 2007). Chronic Deep Brain Stimulation (DBS) of subgenual areas has yielded limited but promising initial results in small samples of TRD patients (Mayberg et al, 2005;Holtzheimer et al, 2012). In a systematic review and exploratory meta-analysis based on four observational studies in severe chronic TRD, twelvemonth response and remission rates were almost 40% and over 26% respectively (Berlim, McGirr, Van den Eynde, Fleck, & Giacobbe, 2014).…”