Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multi-site, randomized, sham-controlled trial

摘要

: Deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCC) has shown promise as an intervention for patients with chronic, unremitting depression (TRD). To test the safety and efficacy of DBS for TRD, a prospective, randomized, sham-controlled trial was conducted. : 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. : 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. : 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.