Methods: Participants with TRD were implanted with a DBS system targeting bilateral SCC white matter and randomized to six months of active versus sham DBS followed by six months open-label SCC DBS. The primary outcome was response rate at the end of the six-month double-blind phase. Response was defined as a 40% or greater reduction in depression severity from baseline. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients continued to be followed for up to 24 months.
Findings: Prior to the futility analysis, 90 participants were randomized to active (N=60) versus sham (N=30) stimulation. Both groups showed improvement, but there was no statistically significant difference in response rate during the double-blind, sham-controlled phase. Participants continued to improve during the six months open-label phase. Long-term response and remission rates for all participants receiving active DBS open-label were, respectively, 40% and 19% at 12 months, 51% and 17% at 18 months, and 48% and 25% at 24 months. Twenty-eight patients experienced 39 adverse events; eight of these (in seven patients) were deemed to be related to the study device and/or surgery.
Interpretation: This study confirmed the safety and feasibility of SCC DBS as a treatment for TRD but failed to show statistically significant antidepressant efficacy in a six months double-blind, sham-controlled trial. Long-term (up to 24 months) open-label SCC DBS was associated with a response rate of nearly 50%, with 25% of participants remitted. These rates are clinically meaningful and higher than those expected in this patient population with treatment-as-usual.
- treatment-resistant depression
- deep brain stimulation
- subcallosal cingulate
- subgenual cingulate
- Brodmann Area 25