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Deep Brain Stimulation for Treatment-resistant Depression: Systematic Review of Clinical Outcomes
Open accessAbstract
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 Among the 22 published studies, only 3 were controlled trials, and 2, as yet unpublished, multicenter, randomized, controlled trials evaluating the efficacy of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were recently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.
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“Importantly, the stimulation parameters of DBS are not identical to those typically used in iES functional mapping sessions (although they are similar; see Box 1); moreover, a multicenter clinical trial of subgenual ACC DBS failed to replicate these positive emotional effects (Morishita et al., 2014).”
From Does the Prefrontal Cortex Play an Essential Role in Consciousness? Insights from Intracranial Electrical Stimulation of the Human Brain (2021) · cites this paper as Morishita et al., 2014
In the citing paper
“In MDD, for example, targeting the subgenual cingulate cortex (sgCC) may have modulatory downstream effects on the dACC by propagating stimulation effects through the rostral cingulate cortex (Morishita et al., 2014).”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Morishita et al., 2014
In the citing paper
“More generally, sgCC-DBS appears to be an effective intervention for severe, treatment-resistant MDD.”
From Cortico-striatal-thalamic loop circuits of the salience network: A central pathway in psychiatric disease and treatment (2016) · cites this paper as Morishita et al., 2014
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Cites
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Deep Brain Stimulation for Treatment-Resistant Depression
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., Schwalb, J. M., & Kennedy, S. H. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.014 · Cited by 4,059
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Cingulate function in depression: a potential predictor of treatment response
Mayberg, H. S., Brannan, S. K., Mahurin, R. K., Jerabek, P. A., Brickman, J. S., Tekell, J. L., Silva, J. A., McGinnis, S., Glass, T. G., Martin, C. C., et al. (1997) · NeuroReport · doi:10.1097/00001756-199703030-00048 · Cited by 1,029
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Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.003.0005
Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.002.0007
Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.002.0008
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Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.003.0009
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Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.003.0004
Gallagher, S. (2023) · Oxford University Press eBooks · doi:10.1093/oso/9780198873068.003.0002 · Cited by 1
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Estado del arte: nuevas aplicaciones para la estimulación cerebral profunda.
Roy, H., Green, A. L., & Aziz, T. Z. (2018) · NeuroTarget · doi:10.47924/neurotarget2018128
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Lindquist, M. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13480-7.00012-0
Brain Structures Involved in Major Depressive Disorder
Bennett, M. R. (2024) · Springer eBooks · doi:10.1007/978-981-97-2803-9_8
Neurochemical mechanisms of deep brain stimulation
Liu, H., Witzig, V. S., Tan, S. K. H., & Hescham, S. (2025) · Deep Brain Stimulation · doi:10.1016/j.jdbs.2025.08.002
Sepas, A., Alkafaji, H., Atici, V., Bjarkam, C. R., & Moos, T. (2025) · Qeios · doi:10.32388/47tw5n
The effects of deep brain stimulation on neurochemistry
Hescham, S., Liu, H., Witzig, V. S., & Tan, S. K. H. (2026) · Elsevier eBooks · doi:10.1016/b978-0-323-99742-3.00006-0
Smith, R. J. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-26466-5.00016-7
Next-Generation Neuromodulation for Anxiety: Circuit-Based and Personalized Approaches
O’Rourke, C. M., Selheimer, R. L., Halpern, C. H., & Oathes, D. J. (2026) · Current Psychiatry Reports · doi:10.1007/s11920-026-01702-3
Metadata
- Authors
- Morishita, T., Fayad, S. M., Higuchi, M.-A., Nestor, K. A., & Foote, K. D.
- Affiliations
- UF Health Shands Hospital (US)
- Corresponding author
- Foote, Kelly D.
- Venue
- Neurotherapeutics
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 11
- Issue
- 3
- Pages
- 475-484
- ISSN
- 1878-7479 (ISSN-L)
- PMC
- PMC4121451
- OpenAlex
- W2025929754
- Cited by
- 216
- References
- 80
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 24 · 2022: 7 · 2021: 12 · 2020: 12 · 2019: 12 · 2018: 30 · 2017: 32 · 2016: 37 · 2015: 29 · 2014: 3
- FWCI
- 4.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neurotherapeutics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boston Scientific Corporation
- Nakatomi Foundation
- Otsuka Pharmaceutical
- Topics
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Keywords
- deep brain stimulation, treatment-resistant depression, major depressive disorder, neuromodulation, subgenual anterior cingulate cortex, ventral capsule/ventral striatum, nucleus accumbens, lateral habenula, medial forebrain bundle, DBS targets, response rate, treatment efficacy and safety
- MeSH terms
- Brain, Major Depressive Disorder, Humans, Treatment Outcome, Deep Brain Stimulation
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