Background
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.
Methods
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.
Results
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.
Conclusions
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.
Key words
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Article info
Publication history
Published online: August 19, 2004
Accepted:
June 22,
2004
Received in revised form:
April 27,
2004
Received:
November 5,
2003
Identification
Copyright
© 2004 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
