DBS Teams Struggle with Psychiatric Disorder Trials

by James Cavuoto, editor

July 2015 issue

The potential market for treating psychiatric disorders with deep brain stimulation continues to confound research teams working in the area. Recently released data from two DBS studies offered disappointing results, but investigators and commercial firms still believe there is great potential for treating disorders such as depression and Alzheimer’s disease.

In the current issue of Biological Psychiatry, Darin Dougherty and his colleagues reported the results of the first large-scale, randomized, sham-controlled trial of DBS for treatment-resistant depression. Thirty patients received active DBS or sham stimulation for 16 weeks, targeted at the ventral capsule and ventral striatum, brain regions implicated in reward and motivation. A two-year open-label continuation phase followed. This study, supported by Medtronic and conducted at five medical centers across the U.S., failed to find that DBS reduced depression symptoms better than sham stimulation.

“While initial open-label trials of DBS at the VC/VS target were promising, the results of this first controlled trial were negative,” explained Dougherty, director of neurotherapeutics at Massachusetts General Hospital and associate professor at Harvard Medical School.

Thomas Schlaepfer, an expert on DBS treatment unaffiliated with this study, from Johns Hopkins University and University Hospital Bonn in Germany, wrote a companion piece to this article and commented, “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.”

“This study raises serious questions about the advisability of continuing to stimulate these reward regions in the manner employed in this study,” said John Krystal, editor of Biological Psychiatry. “It is critical to understand that this study is not a universal indictment of DBS 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.”

“Given the degree of response that we have seen in some of the most treatment refractory patients, we agree with Dr. Schlaepfer and Dr. Krystal. Alternative study designs will have to be considered as we conduct future clinical trials in this critical area,” concluded Dougherty.

Meanwhile, Andres Lozano from the Toronto Western Research Institute reported results from Functional Neuromodulation’s ADvance study of DBS of the fornix to treat Alzheimer’s disease. The double-blind study of 42 patients showed no significant difference between control and treatment arms in cognitive performance on the ADAS-cog13 and the CDR-SB measures after one year. Still Lozano, who founded Functional Neuromodulation, plans to continue further study of DBS for Alzheimer’s, pointing out that the ADvance study was primarily intended to show safety and tolerability.

Helen Mayberg of Emory University also intends to continue pursuing DBS for depression. At the recent NeuroFutures meeting [see conference report, p7], she said she obtained local Medicare reimbursement with an IDE in place for her DBS trials. She said some clinicians may be using DBS systems off-label for depression.