Potential surgical targets for deep brain stimulation in treatment-resistant depression

Object. The goal of this study was to evaluate the definition of treatment-resistant depression (TRD), review the literature regarding deep brain stimulation (DBS) for TRD, and identify potential anatomical and functional targets for future widespread clinical application. Methods. A comprehensive literature review was performed to determine the current status of DBS for TRD, with an emphasis on the scientific support for various implantation sites. Results. The definition of TRD is presented, as is its management scheme. The rationale behind using DBS for depression is reviewed. Five potential targets have been identified in the literature: ventral striatum/nucleus accumbens, subgenual cingulate cortex (area 25), inferior thalamic peduncle, rostral cingulate cortex (area 24a), and lateral habenula. Deep brain stimulation electrodes thus far have been implanted and activated in only the first 3 of these structures in humans. These targets have proven to be safe and effective, albeit in a small number of cases. Conclusions. Surgical intervention for TRD in the form of DBS is emerging as a viable treatment alternative to existing modalities. Although the studies reported thus far have small sample sizes, the results appear to be promising. Various surgical targets, such as the subgenual cingulate cortex, inferior thalamic peduncle, and nucleus accumbens, have been shown to be safe and to lead to beneficial effects with various stimulation parameters. Further studies with larger patient groups are required to adequately assess the safety and efficacy of these targets, as well as the optimal stimulation parameters and long-term effects.