The DOI matches its Crossref record; 69 of the 70 references it cites were found in a registry or an index.
VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms
Abstract
Currently available therapeutic interventions for treatment-resistant depression, including switch, combination, and augmentation strategies, are less than ideal. Observations of mood elevation during vagus nerve stimulation (VNS) therapy for pharmacoresistant epilepsy suggested a role for VNS therapy in refractory major depression and prompted clinical investigation of this neurostimulation modality. The VNS Therapy System has been available for treatment of pharmacoresistant epilepsy since 1997 and was approved by the US Food and Drug Administration for treatment-resistant depression in July, 2005. The physiology of the vagus nerve, mechanics of the VNS Therapy System, and efficacy and safety in pharmacoresistant epilepsy are reviewed. Promising results of VNS therapy for treatment-resistant depression have been forthcoming from both acute and long-term studies, evidenced in part by progressive improvements in depression rating scale scores during the 1st year of treatment with maintenance of response thereafter. VNS therapy is well tolerated in patients with either pharmacoresistant epilepsy or treatment-resistant depression. As in epilepsy, the mechanisms of VNS therapy of treatment-resistant depression are incompletely understood. However, evidence from neuroimaging and other studies suggests that VNS therapy acts via innervation of the nucleus tractus solitarius, with secondary projections to limbic and cortical structures that are involved in mood regulation, including brainstem regions that contain serotonergic (raphe nucleus) and noradrenergic (locus ceruleus) perikarya that project to the forebrain. Mechanisms that mediate the beneficial effects of VNS therapy for treatment-resistant depression remain obscure. Suggestions for future research directions are described.
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“Whether by activating nerves through electrical stimulation or by reading their electrical signals, nerve neuroprosthetics offer a myriad of applications such as the control of bladder function (Brindley et al., 1982), management of depression (Nemeroff et al., 2006), and restoration of sensory perception in amputees (D'Anna et al., 2019).”
From Foreign Body Reaction to Implanted Biomaterials and Its Impact in Nerve Neuroprosthetics (2021) · cites this paper as Nemeroff et al., 2006
In the citing paper
“Through direct or indirect anatomic connections via the NTS, the vagus nerve has structural connections with several mood regulating limbic and cortical brain areas (82).”
From Vagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders (2018) · cites this paper as [82]
Citations
Cites
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How do you feel? Interoception: The sense of the physiological condition of the body
Craig, A. D. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn894 · Cited by 6,006
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
Self-citationNibuya, M., Morinobu, S., & Duman, R. (1995) · The Journal of Neuroscience · doi:10.1523/jneurosci.15-11-07539.1995 · Cited by 2,109
Functional and chemical anatomy of the afferent vagal system
Berthoud, H.-R., & Neuhuber, W. L. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00215-0 · Cited by 1,280
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
Self-citationVagus nerve stimulation therapy for partial-onset seizures
Handforth, A., DeGiorgio, C. M., Schachter, S. C., Uthman, B. M., Naritoku, D. K., Tecoma, E. S., Henry, T. R., Collins, S. D., Vaughn, B. V., Gilmartin, R. C., et al. (1998) · Neurology · doi:10.1212/wnl.51.1.48 · Cited by 1,107
Self-citationNeuropsychopharmacology: The Fifth Generation of Progress
Sagduyu, K. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.7.1251-a · Cited by 1,023
Neuropsychopharmacology : The Fifth Generation of Progress
Davis, K. L., Charney, D. S., Coyle, J. T., & Nemeroff, C. B. (2002) · Lippincott Williams & Wilkins eBooks · Cited by 747
Self-citationLong-term treatment with vagus nerve stimulation in patients with refractory epilepsy
Morris, G. L., Mueller, W. M., & The Vagus Nerve Stimulation Study Group E–E (1999) · Neurology · doi:10.1212/wnl.53.8.1731 · Cited by 727
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Bravo, J. A., Forsythe, P., Chew, M. V., Escaravage, E., Savignac, H. M., Dinan, T. G., Bienenstock, J., & Cryan, J. F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102999108 · Cited by 3,888
Interoception and Mental Health: A Roadmap.
Khalsa, S. S., Adolphs, R., Cameron, O. G., Critchley, H. D., Davenport, P. W., Feinstein, J. S., Feusner, J. D., Garfinkel, S. N., Lane, R. D., Mehling, W. E., et al. (2018) · Biological psychiatry. Cognitive neuroscience and neuroimaging · doi:10.1016/j.bpsc.2017.12.004 · Cited by 1,453
Self-citationVagus Nerve as Modulator of the Brain–Gut Axis in Psychiatric and Inflammatory Disorders
Breit, S., Kupferberg, A., Rogler, G., & Hasler, G. (2018) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00044 · Cited by 1,189
“Through direct or indirect anatomic connections via the NTS, the vagus nerve has structural connections with several mood regulating limbic and cortical brain areas (82).”
BackgroundMalhi, 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
“A small series of studies has evaluated whether VNS has antidepressant effects (Nemeroff et al., 2006), and it appears to produce some antidepressant response but this emerges slowly and only in a minority of patients.”
BackgroundStreeter, C. C., Gerbarg, P. L., Saper, R. B., Ciraulo, D. A., & Brown, R. P. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.01.021 · Cited by 694
Metadata
- Authors
- Nemeroff, C. B., Mayberg, H. S., Krahl, S. E., McNamara, J., Frazer, A., Henry, T. R., George, M. S., Charney, D. S., & Brannan, S. K.
- Affiliations
- Emory University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Duke Medical Center (US)
- The University of Texas at San Antonio Health Science Center (US)
- Medical University of South Carolina (US)
- VA Greater Los Angeles Healthcare System (US)
- Corresponding author
- Nemeroff, Charles B
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2006-04-19
- Volume
- 31
- Issue
- 7
- Pages
- 1345-1355
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2094533610
- Cited by
- 496
- References
- 70
- Citations by year
- 2026: 29 · 2025: 34 · 2024: 37 · 2023: 45 · 2022: 33 · 2021: 26 · 2020: 10 · 2019: 24 · 2018: 27 · 2017: 16 · 2016: 28 · 2015: 25 · 2014: 14 · 2013: 17 · 2012: 22
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Update notices
- erratum (2006-07-31)
- Open access
- closed
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- vagus nerve stimulation, treatment-resistant depression, drug-resistant epilepsy, nucleus tractus solitarius, serotonergic projections, noradrenergic projections, mood regulation, neurostimulation, treatment efficacy and safety
- MeSH terms
- Animals, Major Depressive Disorder, Drug Resistance, Electric Stimulation Therapy, Evaluation Studies as Topic, Humans, Neurobiology, Time Factors, Vagus Nerve
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