Commentary on the Continued Investigational Status of DBS for Psychiatric Indications.

Behavioral disorders exact a tragic toll on patients, families, and society. Consequently, the search for better treatments is a public health priority. Recent research promises to lead to advances in psychiatric treatment that may include implantation of deep brain stimulation (DBS) devices. In this commentary, the authors discuss how promising results from initial pilot studies of DBS in treatment-resistant depression (TRD) were not validated in 2 randomized, controlled, multicenter trials. Reliance on pilot data may have contributed to the selection of primary efficacy endpoints that were not achieved, and to the underestimation of adverse events and device-related complications. Published data on the population prevalence of affective disorders also may have led sponsors to overestimate the number of patients with TRD who were candidates for DBS therapy. Consequently, a more complete discussion of certain aspects of the depression trials may allow a realistic appraisal of the clinical and ethical situation of DBS therapy for TRD in a US regulatory context. A US regulatory perspective also may clarify the clinical research and reimbursement consequences of the Humanitarian Device Exemption (HDE) approval status of DBS for obsessive-compulsive disorder (OCD). Retrospective analyses akin to failure modes and effects analysis in engineering may clarify unexpected results in the DBS depression trials. Recent research suggests that subject selection in future trials may be augmented by advanced neuroimaging methods. For the present, the noncommercial research status of DBS to treat depression and the HDE status for OCD appear likely to remain in place.