Cited by 496Vagus Nerve Stimulation ResearchDeep Brain Stimulation and Movement DisordersTreatment of Major Depression

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VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms

Nemeroff, Charles B, Mayberg, Helen S, Krahl, Scott E, McNamara, James, Frazer, Alan, Henry, Thomas R, George, Mark S, Charney, Dennis S, Brannan, Stephen K·2006·Neuropsychopharmacology

DOI 10.1038/sj.npp.1301082

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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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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: Nemeroff, Charles B
Mayberg, Helen S
McNamara, James
Frazer, Alan
Henry, Thomas R
George, Mark S
Charney, Dennis S
Brannan, Stephen K
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2006-04-19
Volume: 31
Issue: 7
Pages: 1345-1355
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/sj.npp.1301082
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
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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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VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms

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