It takes time to tune

In a recent issue of JAMA Psychiatry, Bergfeld et al., report the results of an investigator-initiated trial of bilateral deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) for treatment of treatment-resistant depression (TRD) (1). The results of this trial indicate that DBS of vALIC produces an antidepressant response that slowly accumulates over the course of a year and rapidly dissipates when stimulation is discontinued. This is encouraging and brings hope to patients with a debilitating depression who have exhausted most currently available treatment options. Indeed, the patients selected for this trial were particularly refractory, having failed electroconvulsive therapy (ECT) as well as numerous pharmacotherapeutic approaches, including two selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and lithium augmentation. Despite reports of recently failed industry-sponsored trials of DBS for treatment of TRD (2,3), the medical field has an obligation to continue to investigate potential treatments for this group of severely afflicted patients. Although the results of this trial inspire some hope for an effective treatment for TRD, this hope comes with a caveat of caution driven by two recently failed trials (2,3) as well as several unique aspects of this trial that raise questions of how to move the field of invasive neuromodulation for TRD forward.