title: A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders.
abstract: BACKGROUND
  Vagus nerve stimulation (VNS) is an effective anticonvulsant device and has shown antidepressant effects in chronic treatment resistant depression. Because the vagus nerve sends information to brain regions important in anxiety regulation (locus coeruleus, orbitofrontal cortex, insula, hippocampus and amygdala), this pathway might be involved in perceiving or manifesting various somatic and cognitive symptoms that characterize anxiety disorders. On the basis of this reasoning and reports of anxiolytic effects of VNS in patients treated for epilepsy and depression, we organized an open-label pilot acute trial of adjunctive VNS on top of stable medications, followed by long-term follow-up, to assess the safety and potential efficacy of VNS for patients with treatment resistant anxiety disorders.
  
  
  METHODS
  Eleven adult outpatients with treatment resistant obsessive-compulsive disorder (OCD), panic disorder (PD), or posttraumatic stress disorder (PTSD) were recruited. Patients had failed several medication trials as well as cognitive behavioral therapy (CBT). All patients were rated with the Hamilton Anxiety Scale (HAM-A) and the clinical global impressions improvement scale (CGI-I). Patients with OCD were also rated with the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Patients were maintained on their current psychotropic medications at fixed doses during the acute 12-week phase. Changes in medications and VNS stimulus parameters were allowed during the long-term follow-up. Response was defined as a 50% or greater improvement on the HAM-A for all patients and a 25% or greater improvement on the Y-BOCS for patients with OCD.
  
  
  RESULTS
  Eleven patients were recruited. Seven patients had a primary diagnosis of OCD, two had PTSD, and one had PD. One OCD patient changed their mind and was never implanted. One patient with OCD withdrew consent before the end of the acute phase, so long-term results were available for nine patients. Three patients were acute responders, based on the HAM-A, and there was some improvement in anxiety ratings over time (with statistically significant improvements at 14 of 18 quarters during long-term follow-up). Of the seven patients with OCD who received stimulation, three were acute responders, based on the Y-BOCS, and there was some improvement in Y-BOCS scores over time (with statistically significant improvements at 7 of 18 quarters during long-term follow-up). VNS was relatively well tolerated. Four years after implantation, four patients (diagnoses two OCD, one PD, one PTSD) were still receiving VNS with continued and sustained improvement in anxiety scores compared with their baseline scores.
  
  
  CONCLUSIONS
  These patients with treatment-resistant anxiety disorders generally tolerated VNS treatment, and there was evidence of acute and long-term improvement in some patients. These open data suggest that further double-blind studies assessing the VNS role in treating anxiety disorders, particularly OCD, may be warranted.
authors.affiliation: Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina 29425, USA. georgem@musc.edu
authors.forename: Mark S
authors.initials: MS
authors.lastname: George
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Ward
authors.forename: Philip T
authors.initials: PT
authors.lastname: Ninan
authors.forename: Mark
authors.initials: M
authors.lastname: Pollack
authors.forename: Ziad
authors.initials: Z
authors.lastname: Nahas
authors.forename: Berry
authors.initials: B
authors.lastname: Anderson
authors.forename: Samet
authors.initials: S
authors.lastname: Kose
authors.forename: Robert H
authors.initials: RH
authors.lastname: Howland
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Goodman
authors.forename: James C
authors.initials: JC
authors.lastname: Ballenger
mesh_terms: D000328:Adult; D001008:Anxiety Disorders / Q000503:physiopathology / Q000628:therapy*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D015928:Cognitive Behavioral Therapy; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000628:therapy; D016584:Panic Disorder / Q000628:therapy; D010865:Pilot Projects; D011569:Psychiatric Status Rating Scales; D013313:Stress Disorders, Post-Traumatic / Q000628:therapy; D017211:Treatment Failure; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000379:methods*; D055815:Young Adult