Deep brain stimulation for treatment-resistant depression: systematic review of clinical outcomes
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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 Among the 22 published studies, only 3 were controlled trials, and 2, as yet unpublished, multicenter, randomized, controlled trials evaluating the efficacy of subgenual cingulate cortex and ventral striatum/ventral capsule DBS were recently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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A multicenter clinical trial of subgenual ACC DBS failed to replicate the positive emotional effects.
“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 MDD, targeting the sgCC may have modulatory downstream effects on the dACC by propagating stimulation effects through the rostral cingulate cortex.
“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
sgCC-DBS appears to be an effective intervention for severe, treatment-resistant MDD.
“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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- 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 › Neurology › Neurological disorders and treatments
- Health Sciences › Medicine › Pharmacology › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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