A pilot study of vagus nerve
stimulation (VNS) for treatment-resistant anxiety disorders
Received 25 August 2007; received in revised form 22 January 2008;
accepted 19 February 2008.
published online 12 May 2008.
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.
a Department of Psychiatry, Medical University of
South Carolina, Charleston, South Carolina
b Department of Psychiatry, University of Florida
School of Medicine, Gainesville, Florida
c Department of Psychiatry and Behavioral
Sciences, Emory University School of Medicine, Atlanta, Georgia
d Department of Psychiatry, Massachusetts General
Hospital, Boston, Massachusetts
e Western Psychiatric Institute, Pittsburgh,
Pennsylvania
 Address
reprints requests to: Dr. Mark S. George, 502N, IOP, Medical University
of South Carolina, 67 President Street, Charleston, SC 29425.
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.2008.02.00
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ABSTRACT