Volume 1, Issue 2 , Pages 112-121, April 2008
A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders
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.
Keywords: vagus nerve stimulation (VNS), anxiety disorder, obsessive compulsive disorder, panic disorder, posttraumatic stress disorder, clinical trial, efficacy, side effects
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This study was supported in part by grants from Cyberonics, Inc. Data were collected by Quintiles Transnational Corp. Statistical analyses were performed by Amara K. Jayewardene, MS, and John Allen, Jr., PhD, of Cyberonics, Inc., manufacturer of the VNS Therapy System and reviewed by the authors. Susan E. Siefert, ELS, CBC, also of Cyberonics, assisted with the development of the manuscript.
Dr. George has received research grants from Cyberonics, and is on the Cyberonics Depression and Mechanism of Action Scientific Advisory Boards.
Dr. Nahas has received research grants and speaking fees from Cyberonics.
Dr. Robert H. Howland has received research support from Aspect Medical Systems; Bristol-Myers Squibb; Cyberonics; Forest; Cederroth; National Institutes of Mental Health; National Center for Complementary and Alternative Medicine. He has received speaking fees from Wyeth; Bristol-Myers Squibb; AstraZeneca; Cyberonics.
Amara Jayewardene, MS, John Allen, Jr, PhD, and Susan E. Siefert, ELS, CBC, are employees of Cyberonics.
Dr. Allen and Ms Siefert own Cyberonics stock. Dr. Ninan is now an employee of Wyeth Pharmaceuticals.
Dr. Pollack is a paid adviser, consultant or speaker for AstraZeneca, Brain Cells Inc, Bristol Myers Squibb, Cephalon, Forest Laboratories, GlaxoSmithKline, Janssen, Jazz Pharmaceuticals, Eli Lilly, Medavante, Neurocrine, Neurogen, Novartis, Otsuka Pharmaceuticals, Pfizer, Predix, Roche, Laboratories, Sanofi, Sepracor, Solvay, Tikvah Therapeutics, Transcept Inc, UCB Pharma, and Wyeth. He has equity stake in Medavante and Mensante Corporation. He has received research grants from Bristol Myers Squibb, Cephalon, Cyberonics, Forest Laboratories, GlaxoSmithKline, Janssen, Eli Lilly, NARSAD, NIDA NIMH, Pfizer, Sepracor, UCB Pharma, and Wyeth.
Although Cyberonics sponsored the trial, the authors were involved in initial study design, data collection, manuscript writing, and have had full access to the data.
Aspects of this trial have been previously reported in poster format at:
George MS, et al: Vagus nerve stimulation (VNS) shows potential therapeutic benefit for severe anxiety disorders in an initial open trial. 41st American College of Neuropsychopharmacology Annual Meeting. December 2002.
Ward H, et al: Treatment-refractory obsessive-compulsive disorder: potential benefit of VNS therapy. 23rd Annual Conference of the Anxiety Disorders Association of America. March 2003.
George MS, et al: Open trial of VNS therapy in severe anxiety disorder. 156th American Psychiatric Association Annual Meeting. May 17-22, 2003, San Francisco, California.
PII: S1935-861X(08)00003-X
doi:10.1016/j.brs.2008.02.001
© 2008 Elsevier Inc. All rights reserved.
Volume 1, Issue 2 , Pages 112-121, April 2008
