Deep brain stimulation (DBS) is an invasive therapy in which electrodes are surgically placed into the brain and deliver continuous electrical stimulation. It was originally developed for Parkinson’s disease and other movement disorders. As evidence emerged that certain mental disorders involved abnormal function of specific brain nuclei, multiple investigators launched trials of DBS for mental disorders, particularly major depression (MDD) and obsessive-compulsive disorder (OCD). While open-label results were promising, recent large well-designed clinical trials in MDD have failed. We review the result of major DBS studies to date in psychiatry and what they have taught us about DBS’ safety and efficacy. We further review a variety of animal and human neuroscience studies that have started to shed light on DBS’ mechanisms of action at multiple brain targets. From these, we identify major trends that are likely to drive psychiatric DBS development in the coming decade, including “closed-loop” responsive stimulation, biomarker-based patient selection, and a better modeling of phenotypic heterogeneity within mental disorders. We conclude that on balance, DBS remains promising as a psychiatric treatment, but recent evidence highlights a clear need for further development and a better understanding of mechanisms.
Bibliographical noteFunding Information:
Darin Dougherty received a federal research grant from DARPA, a device donation from Medtronic, funding from the NIH, payment from Cyberonics for presentations related to vagus nerve stimulation, and payment from Medtronic for training physicians in the use of DBS for OCD. Alik Widge received a federal research grant from DARPA, an individual fellowship from Picower Family Foundation, and funding from the NIH, and Widge has patents applied related to novel deep brain stimulation treatments.
DDD has received research support from and served on advisory panels for Medtronic and Cyberonics. Both authors are named inventors on patent applications related to transdiagnostic targeting of brain stimulation interventions and methods for closed-loop deep brain stimulation. Both authors gratefully acknowledge the support of the DARPA SUBNETS program, cooperative agreement W911NF-14-2-0045. ASW is also supported by the Picower Family Foundation.
- Deep brain stimulation
- Major depression
- Obsessive-compulsive disorder