Results from the first large-scale, randomized, sham-controlled trial of deep brain stimulation for treatment-resistant depression did not indicate significant efficacy at the end of the 16-week controlled phase.
“More recently, [deep brain stimulation] has been investigated as a potential neurosurgical intervention for psychiatric patients with obsessive-compulsive disorder (OCD) and [treatment-resistant depression]. Relying on the same devices and procedures used to treat movement disorders and OCD, different research groups have investigated the potential antidepressant efficacy of [deep brain stimulation] at various anatomical targets including the ventral capsule/ventral striatum (VC/VS), subgenual cingulate cortex (Cg25), nucleus accumbens, medial forebrain bundle, and lateral habenula,” Darin D. Dougherty, MD, of Massachusetts General Hospital and Harvard Medical School, and colleagues wrote.
Darin D. Dougherty
Researchers randomly assigned 30 patients with treatment-resistant depression to active or sham deep brain stimulation for 16 weeks, followed by an open-label continuation phase. Treatment response was defined as a 50% or greater improvement on the Montgomery-Åsberg Depression Rating Scale from baseline.
There were no significant differences in response rates between the active (20%) and control (14.3%) treatment groups.
At 16 weeks, Montgomery-Åsberg Depression Rating Scale scores did not significantly differ between groups.
Response rates during the open-label continuation phase were 20% at 12 months, 26.7% at 18 months and 23.3% at 24 months.
Thomas E. Schlaepfer
“Our findings failed to demonstrate a significant difference between the active and sham-control groups during the blinded phase of the study. It is important to note that the study was insufficiently powered to detect true differences with only 30 subjects,” Dougherty and colleagues wrote. “However, we did find that there was some improvement for the cohort as a whole during the long-term follow-up phase of the study, which is encouraging since these patients had severe and chronic courses of depression that had not responded to a multitude of antidepressant drugs, psychotherapies, and devices.”
“On first sight, this might be seen as a crisis for the whole field of neurostimulation therapies for depression... [but we] believe that these are examples of failed studies and not failed treatments,” Thomas E. Schlaepfer, MD, of Johns Hopkins University and University Hospital Bonn in Germany, said in a press release.
John H. Krystal
John H. Krystal, MD, of Yale School of Medicine and editor of Biological Psychiatry, echoed Schlaepfer’s sentiment. “This study raises serious questions about the advisability of continuing to stimulate these reward regions in the manner employed in this study,” he said in the release. “It is critical to understand that this study is not a universal indictment of [deep brain stimulation] as a strategy for depression. It may turn out that stimulating other brain regions or stimulating these regions in different ways could provide important benefit.” – by Amanda Oldt
Disclosure: The study was funded by Medtronic, Inc. All authors received research support from Medtronic, Inc. Dougherty reports receiving honoraria from Reed Elsevier and Medtronic. He also reports serving as a consultant to Medtronic and receiving grant/research support from Eli Lilly, Cyberonics and Roche. Please see the full study for a list of all other authors’ relevant financial disclosures.