Not Giving in to Depression
In the two and a half years since this publication first reported the failure of the BROADEN trial of DBS for depression [NBR Dec13 p7], there has been considerable progress in advancing our understanding of how DBS modulates depression circuits. Unfortunately, there has been little effort by neuromodulation firms to commercialize new DBS therapies for depression. In part, this is because the BROADEN failure and an earlier failure by Medtronic of VC/VS DBS has dampened enthusiasm and risk-taking at medical device firms. Also, St. Jude Medical still owns much of the intellectual property and doesn’t seem too eager to part with it. The prospects seem bleak that Abbott will move depression to the front burner when it completes its merger.
Many of the issues surrounding failed clinical trials of DBS for psychiatric disorders came to the surface during a lively discussion period at the recent Neuromodulation: The Science meeting [see Conference Report, p7]. Panelists Ali Rezai from Ohio State, Warren Grill from Duke, Cameron McIntyre from Case, Andres Lozano from University of Toronto, and Brian Kopell from Mount Sinai offered their views on what’s necessary for a successful clinical trial of DBS for depression. The panel mentioned further elucidation of meaningful tracts, better understanding of differing etiologies, useful biomarkers to help patient selection, and directional leads with more options for contact selection as key needs. Robert Gross, a professor of neurosurgery at Emory University, took aim at the concept of randomized control trials. “What’s good for pharma is not necessarily what’s good for devices,” he said, pointing out that neuromodulation responder rates have a tendency to improve long after the completion of a trial.
Though she was not at the meeting, Gross’s colleague Helen Mayberg commented on a Dutch trial of DBS of the ventral anterior limb of the internal capsule for depression published in JAMA Psychiatry last month. Though the 40 percent open-label response rate might not seem that great, Mayberg and her colleagues Patricio Riva-Posse and Andrea Crowell at Emory’s department of psychiatry praised the Dutch team for conducting a second phase that compared the effects of sham vs. active stimulation. The Dutch study “further highlights the need to seriously consider customized trial designs in planning any invasive device trials, be it DBS, vagus nerve stimulation, or a future novel technology,” Mayberg et al said in an editorial in the journal. The reviewers also highlighted the risk of a rigidly fixed optimization period. “It’s important to avoid a one size fits all approach,” they wrote.
Given the increased understanding of depression circuits and patient variability that we now have, we continue to believe the time is ripe for a concerted effort to commercialize DBS for depression.
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