@article{0dd817e95614442fafc5c7ff68d70681,
title = "Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients",
abstract = "Vagus nerve stimulation (VNS) has shown promising antidepressant effects in treatment-resistant depression, but the mechanisms of action are not known. Cerebrospinal fluid (CSF) studies in epilepsy patients show that VNS alters concentrations of monamines and γ-aminobutyric acid (GABA), neurotransmitter systems possibly involved in the pathogenesis of depression. Twenty-one adults with treatment-resistant, recurrent, or chronic major depression underwent standardized lumbar puncture for collection of 12 mL CSF on three separate but identical procedure days during participation in the VNS D-02 clinical trial. All subjects remained on stable regimens of mood medications. Collections were made at baseline (2 weeks after surgical implantation but before device activation), week 12 (end of the acute-phase study), and week 24. Cerebrospinal fluid concentrations of norepinephrine (NE), 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) were determined with high-performance liquid chromatography. Concentrations of GABA were assayed with mass spectrometry. Comparison of sham versus active VNS revealed a significant (mean 21%) VNS-associated increase in CSF HVA. Mean CSF concentrations of NE, 5-HIAA, MHPG, and GABA did not change significantly. Higher baseline HVA/5-HIAA ratio predicted worse clinical outcome. Although several of the CSF neurochemical effects we observed in this VNS study were similar to those described in the literature for antidepressants and electroconvulsive therapy, the results do not suggest a putative antidepressant mechanism of action for VNS.",
keywords = "Cerebrospinal fluid, GABA, depression, mechanism, monoamines, neurotransmitters, norepinephrine, vagus nerve stimulation",
author = "Carpenter, {Linda L.} and Moreno, {Francisco A.} and Kling, {Mitchel A.} and Anderson, {George M.} and Regenold, {William T.} and Labiner, {David M.} and Price, {Lawrence H.}",
note = "Funding Information: Support for this study was provided by Cyberonics. LLC discloses receipt of grant/research support from Cyberonics (Investigator-Initiated Research Grant), Pfizer, Merck, Corcept Therapeutics, Cephalon, and Medtronic; speakers bureau honoraria from Cyberonics, Abbott Laboratories, Pfizer, Somerset, Organon, and Wyeth; and payment for consultant services to Organon, Cephalon, GlaxoSmithKline, and Pfizer. FAM discloses receiving grant support from the National Institute of Mental Health, the U.S. Food and Drug Administration, Sigma-Tao, Eli-Lilly, Pfizer, Cyberonics, Novartis, and Pharmacia and Upjohn; speakers bureau honorariua from Solvay, Organon, Eli-Lilly, Pfizer, Astra-Zeneca, Forrest, Wyeth-Ayerst, and Cyberonics; and payment for consulting services to Forrest, Eli-Lilly, Astra-Zeneca, and Solvay. MAK discloses receipt of grant support from Cyberonics, Eli Lilly, and Merck; and speakers bureau or advisory board honoraria from Janssen, AstraZeneca, Bristol-Myers Squibb, Pfizer, Forest, and Cyberonics. GMA discloses payment from Novartis for consulting services. WTR discloses receipt of research grants from Pfizer, Sigma Tau Pharmaceuticals, Cyberonics, and Eisai; and speakers bureau honoraria from Pfizer and Eisai. DML discloses receipt of research grants from Abbott Laboratories, Cyberonics, Elan Pharma, GlaxoSmithKline, Novartis, Ortho McNeil, Pfizer, and UCB Pharma; speakers bureau honoraria from Abbott Laboratories, Cyberonics, Elan Pharma, GlaxoSmithKline, Novartis, Ortho McNeil, Pfizer, Shire, and UCB Pharma; and payment for consulting services to Cyberonics, Elan Pharma, GlaxoSmithKline, Novartis, Ortho McNeil, Pfizer, and UCB Pharma. LHP receipt of research support from Merck, Thuris, Medtronic, Cyberonics, and Cephalon; speakers bureau honoraria from GlaxoSmithKline, and AstraZeneca; and payment for consulting services to Pfizer, GlaxoSmithKline, and AstraZeneca. ",
year = "2004",
month = sep,
day = "15",
doi = "10.1016/j.biopsych.2004.06.025",
language = "English (US)",
volume = "56",
pages = "418--426",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier Inc.",
number = "6",
}