The article by Bergfeld et al1 in this issue of JAMA Psychiatry reports the results of an investigator-initiated trial of deep brain stimulation (DBS) to the ventral anterior limb of the internal capsule (vALIC) for treatment-resistant depression (TRD). Deep brain stimulation for TRD is an evolving experimental therapy with a range of different gray and white matter targets currently under study.2 Although this is not the first report of vALIC DBS for TRD, it used a robust but underutilized trial design: an open-label, extended optimization period followed by a blinded, randomized, discontinuation experiment once a stable response was achieved. This design is in contrast to the more typical blinded randomization at stimulation onset used in most psychiatry treatment trials. The 40% open-label response rate demonstrated by Bergfeld et al1 is similar to that reported in the first open-label study of vALIC DBS for TRD.3 However, it is the second phase of this study—discriminating effects of active vs sham stimulation—that is most compelling. This critical differential effect was not demonstrated in the recent industry-sponsored randomized clinical trial4 that used the more traditional, up-front active vs sham design. With increasing interest in targeted circuit modulation for depression and other psychiatric disorders, the Bergfeld et al1 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 HS, Riva-Posse P, Crowell AL. Deep Brain Stimulation for DepressionKeeping an Eye on a Moving Target. JAMA Psychiatry. 2016;73(5):439-440. doi:10.1001/jamapsychiatry.2016.0173