, Volume 11, Issue 3, pp 475–484 | Cite as

Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes

  • Takashi Morishita
  • Sarah M. Fayad
  • Masa-aki Higuchi
  • Kelsey A. Nestor
  • Kelly D. Foote


Major depressive disorder (MDD) is a widespread, severe, debilitating disorder that markedly diminishes quality of life. Medication is commonly effective, but 20–30 % of patients are refractory to medical therapy. The surgical treatment of psychiatric disorders has a negative stigma associated with it owing to historical abuses. Various ablative surgeries for MDD have been attempted with marginal success, but these studies lacked standardized outcome measures. The recent development of neuromodulation therapy, especially deep brain stimulation (DBS), has enabled controlled studies with sham stimulation and presents a potential therapeutic option that is both reversible and adjustable. We performed a systematic review of the literature pertaining to DBS for treatment-resistant depression to evaluate the safety and efficacy of this procedure. We included only studies using validated outcome measures. Our review identified 22 clinical research papers with 5 unique DBS approaches using different targets, including nucleus accumbens, ventral striatum/ventral capsule, subgenual cingulate cortex, lateral habenula, inferior thalamic nucleus, and medial forebrain bundle. Among the 22 published studies, only 3 were controlled trials, and 2, as yet unpublished, multicenter, randomized, controlled trials evaluating the efficacy of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were recently discontinued owing to inefficacy based on futility analyses. Overall, the published response rate to DBS therapy, defined as the percentage of patients with > 50 % improvement on the Hamilton Depression Rating Scale, is reported to be 40–70 %, and outcomes were comparable across studies. We conclude that DBS for MDD shows promise, but remains experimental and further accumulation of data is warranted.


Deep brain stimulation Major depressive disorder Ventral capsule Ventral striatum Brodmann area 25 Subgenual cingulate Nucleus accumbens 



This work was supported, in part, by a Grant-in Aid for Clinical Research from St. Luke’s Life Science Institute of Japan and Japan Society for Promotion of Science. T. Morishita has no disclosures related to this study. He has received grant support from Nakatomi foundation, St. Luke’s Life Science Institute of Japan, and Japan Society for Promotion of Science in Japan. He has received honoraria from Otsuka pharmaceutical as a consultant within the past 12 months K.D. Foote has received grants from Medtronic in support of his functional neurosurgery fellowship and his research. He has also received research grants from Neuropace, St. Jude, and Boston Scientific. He has no conflict of interest pertaining to this project. The other authors have no conflicts of interest to declare.

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2014

Authors and Affiliations

  • Takashi Morishita
    • 1
  • Sarah M. Fayad
    • 2
  • Masa-aki Higuchi
    • 3
  • Kelsey A. Nestor
    • 1
  • Kelly D. Foote
    • 1
  1. 1.Department of Neurosurgery, McKnight Brain InstituteUniversity of Florida College of Medicine/Shands Hospital, Center for Movement Disorders and NeurorestorationGainesvilleUSA
  2. 2.Department of Psychiatry, McKnight Brain InstituteUniversity of Florida College of Medicine/Shands Hospital, Center for Movement Disorders and NeurorestorationGainesvilleUSA
  3. 3.Department of Neurology, McKnight Brain InstituteUniversity of Florida College of Medicine/Shands Hospital, Center for Movement Disorders and NeurorestorationGainesvilleUSA

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