Transcutaneous vagus nerve stimulation for the treatment of depression: a study protocol for a double blinded randomized clinical trial

BackgroundDepressive disorders are the most common form of mental disorders in community and health care settings. Unfortunately, the treatment of Major Depressive Disorder (MDD) is far from satisfactory. Vagus nerve stimulation (VNS) is a relatively new and promising physical treatment for depressive disorders. One particularly appealing element of VNS is the long-term benefit in mood regulation. However, because this intervention involves surgery, perioperative risks, and potentially significant side effects, this treatment has been limited to those patients with treatment-resistant depression who have failed medication trials and exhausted established somatic treatments for major depression, due to intolerance or lack of response.This double-blinded randomized clinical trial aims to overcome these limitations by introducing a novel method of stimulating superficial branches of the vagus nerve on the ear to treat MDD. The rationale is that direct stimulation of the afferent nerve fibers on the ear area with afferent vagus nerve distribution should produce a similar effect as classic VNS in reducing depressive symptoms without the burden of surgical intervention.DesignOne hundred twenty cases (60 males) of volunteer patients with mild and moderate depression will be randomly divided into transcutaneous vagus nerve stimulation group (tVNS) and sham tVNS group. The treatment period lasts 4 months and all clinical and physiological measurements are acquired at the beginning and the end of the treatment period.DiscussionThis study has the potential to significantly extend the application of VNS treatment for MDD and other disorders (including epilepsy, bipolar disorder, and morbid obesity), resulting in direct benefit to the patients suffering from these highly prevalent disorders. In addition, the results of this double-blinded clinical trial will shed new light on our understanding of acupuncture point specificity, and development of methodologies in clinical trials of acupuncture treatment.Trials registrationClinical Trials. ChiCTR-TRC-11001201 http://www.chictr.org/cn/

[1]  T. Koepsell,et al.  Lessons from a Trial of Acupuncture and Massage for Low Back Pain: Patient Expectations and Treatment Effects , 2001, Spine.

[2]  A. Rush.  Vagus nerve stimulation: clinical results in depression , 2002 .

[3]  M. Fillmore,et al.  Expected effect of caffeine on motor performance predicts the type of response to placebo , 2007, Psychopharmacology.

[4]  E. Peuker,et al.  The nerve supply of the human auricle , 2002, Clinical anatomy.

[5]  Ted J. Kaptchuk,et al.  The Placebo Effect in Alternative Medicine: Can the Performance of a Healing Ritual Have Clinical Significance? , 2002, Annals of Internal Medicine.

[6]  Barry R. Rittberg,et al.  Effects of 12 Months of Vagus Nerve Stimulation in Treatment-Resistant Depression: A Naturalistic Study , 2005, Biological Psychiatry.

[7]  A new choice for the treatment of epilepsy: electrical auricula-vagus-stimulation. , 2011, Medical hypotheses.

[8]  T L Faber,et al.  Brain Blood Flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: I. Acute Effects at High and Low Levels of Stimulation , 1998, Epilepsia.

[9]  P. Mohr,et al.  The Application of Vagus Nerve Stimulation and Deep Brain Stimulation in Depression , 2011, Neuropsychobiology.

[10]  E. G. Ventureyra,et al.  Transcutaneous vagus nerve stimulation for partial onset seizure therapy , 2000, Child's Nervous System.

[11]  W. Sperling,et al.  Clinical Benefits and Cost Effectiveness of Vagus Nerve Stimulation in a Long-term Treatment of Patients with Major Depression , 2009, Pharmacopsychiatry.

[12]  W. Maier,et al.  Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: An exploratory approach , 2005, Psychiatry Research: Neuroimaging.

[13]  J. Kornhuber,et al.  BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation , 2007, Journal of Neural Transmission.

[14]  F. J. Burke.  Physical treatments in psychiatry. , 1974, Nursing times.

[15]  C. Epstein,et al.  Brain Blood‐flow Alterations Induced by Therapeutic Vagus Nerve Stimulation in Partial Epilepsy: II. Prolonged Effects at High and Low Levels of Stimulation , 2004, Epilepsia.

[16]  C. Murray,et al.  Burden of disease--implications for future research. , 2001, JAMA.

[17]  Alan Frazer,et al.  VNS Therapy in Treatment-Resistant Depression: Clinical Evidence and Putative Neurobiological Mechanisms , 2006, Neuropsychopharmacology.

[18]  L. Kiloh,et al.  Physical treatments in psychiatry , 1988 .

[19]  C. Nemeroff,et al.  Erratum: VNS therapy in treatment-resistant depression: Clinical evidence and putative neurobiological mechanisms (Neuropsychopharmacology (2006) 31 (1345-1355) DOI: 10.1038/sj.npp.1301082) , 2006 .

[20]  David Aaron,et al.  A New Concept , 1974 .

[21]  Mark P. Jensen,et al.  Motivation and expectancy factors in symptom perception: a laboratory study of the placebo effect. , 1991, Psychosomatic medicine.

[22]  Xin-Yan Gao,et al.  Investigation of specificity of auricular acupuncture points in regulation of autonomic function in anesthetized rats , 2008, Autonomic Neuroscience.

[23]  Thomas R. Henry,et al.  Therapeutic mechanisms of vagus nerve stimulation , 2002, Neurology.

[24]  Eduard Vieta,et al.  Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review. , 2008, Journal of affective disorders.

[25]  Mustafa M. Husain,et al.  Vagus Nerve Stimulation for Treatment-Resistant Depression: A Randomized, Controlled Acute Phase Trial , 2005, Biological Psychiatry.