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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 Among the 22 published studies, only 3 were controlled trials, and 2, as yet unpublished, multicenter, randomized, controlled trials evaluating the efficacy of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were recently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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Citations
Cites
Hamilton, M. (1960) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.23.1.56 · Cited by 32,817
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Selective Cortical Undercutting As a Means of Modifying and Studying Frontal Lobe Function in Man
Scoville, W. B. (1949) · Journal of neurosurgery · doi:10.3171/jns.1949.6.1.0065 · Cited by 7,374
Rush, A. J., Trivedi, M. H., Wisniewski, S. R., Nierenberg, A. A., Stewart, J. W., Warden, D., Niederehe, G., Thase, M. E., Lavori, P. W., Lebowitz, B. D., et al. (2006) · American Journal of Psychiatry · doi:10.1176/ajp.2006.163.11.1905 · Cited by 5,643
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
Limbic-cortical dysregulation: a proposed model of depression
(1997) · The Journal of Neuropsychiatry and Clinical Neurosciences · doi:10.1176/jnp.9.3.471 · Cited by 1,585
Diagnosis and definition of treatment-resistant depression
Fava, M. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(03)00231-2 · Cited by 1,380
Mayberg, H. S., Brannan, S. K., Tekell, J. L., Silva, J. A., Mahurin, R. K., McGinnis, S., & Jerabek, P. A. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01036-2 · Cited by 1,115
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
Cited by
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Deep brain stimulation: current challenges and future directions
Lozano, A. M., Lipsman, N., Bergman, H., Brown, P., Chabardès, S., Chang, J. W., Matthews, K., McIntyre, C. C., Schlaepfer, T. E., Schulder, M., et al. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0128-2 · Cited by 1,475
Building better biomarkers: brain models in translational neuroimaging
Woo, C.-W., Chang, L. J., Lindquist, M. A., & Wager, T. D. (2017) · Nature Neuroscience · doi:10.1038/nn.4478 · Cited by 1,056
Malhi, G. S., Bassett, D., Boyce, P., Bryant, R., Fitzgerald, P. B., Fritz, K., Hopwood, M., Lyndon, B., Mulder, R., Murray, G., et al. (2015) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867415617657 · Cited by 842
“However, two recent industry sponsored trials have been terminated early due to the lack of positive interim results (Dougherty et al., 2014; Morishita et al., 2014).”
BackgroundCleare, A., Pariante, C., Young, A., Anderson, I., Christmas, D., Cowen, P., Dickens, C., Ferrier, I., Geddes, J., Gilbody, S., et al. (2015) · Journal of Psychopharmacology · doi:10.1177/0269881115581093 · Cited by 759
Peters, S. K., Dunlop, K., & Downar, J. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2016.00104 · Cited by 611
“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).”
Background
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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