Transcutaneous Vagus Nerve Stimulation for the Treatment of Depression: a Study Protocol for a Double Blinded Randomized Clinical Trial

Overview

Journal BMC Complement Altern Med

Publisher Biomed Central

Specialty Rehabilitation Medicine

Date 2012 Dec 18

PMID 23241431

Citations 47

Authors

Pei-Jing Rong

Ji-Liang Fang

Li-Ping Wang

Hong Meng

Jun Liu

Ying-Ge Ma

Hui Ben

Liang Li

Ru-Peng Liu

Zhan-Xia Huang

Yu-Feng Zhao

Xia Li

Bing Zhu

Jian Kong

Affiliations

Soon will be listed here.

Abstract

Background: Depressive 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.

Design: One 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.

Discussion: This 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 Registration: Clinical Trials. ChiCTR-TRC-11001201 http://www.chictr.org/cn/

Citing Articles

Protocol for a nested case-control study: identifying neuroimaging biomarkers for the progression of subclinical depression and qi-stagnation constitution to major depressive disorder in adolescents.

Wang J, Zhang C, Zhang Y, Liu Y, Zhang J, Fang X Front Psychiatry. 2025; 15:1516846.

PMID: 39906680 PMC: 11790624. DOI: 10.3389/fpsyt.2024.1516846.

Transcutaneous Auricular Vagus Nerve Stimulation to Improve Emotional State.

Aranberri Ruiz A Biomedicines. 2024; 12(2).

PMID: 38398009 PMC: 10886536. DOI: 10.3390/biomedicines12020407.

Cervical Manipulation and Koren Specific Technique Emotions Protocol in the Improvement of Intensive Nocturnal Dry Cough: A Case Report.

Chang H Cureus. 2024; 16(1):e51502.

PMID: 38304660 PMC: 10831779. DOI: 10.7759/cureus.51502.

Subdiaphragmatic vagal nerve stimulation attenuates the development of hypertension and alters nucleus of the solitary tract transcriptional networks in the spontaneously hypertensive rat.

Dirr E, Jiracek L, Baekey D, Martyniuk C, Otto K, Zubcevic J Physiol Genomics. 2023; 55(12):606-617.

PMID: 37746712 PMC: 11178265. DOI: 10.1152/physiolgenomics.00016.2023.

Management of auricular transcutaneous neuromodulation and electro-acupuncture of the vagus nerve for chronic migraine: a systematic review.

Fernandez-Hernando D, Fernandez-de-Las-Penas C, Pareja-Grande J, Garcia-Esteo F, Mesa-Jimenez J Front Neurosci. 2023; 17:1151892.

PMID: 37397439 PMC: 10309039. DOI: 10.3389/fnins.2023.1151892.

References

Yang A, Zhang J, Rong P, Liu H, Chen N, Zhu B . A new choice for the treatment of epilepsy: electrical auricula-vagus-stimulation. Med Hypotheses. 2011; 77(2):244-5. DOI: 10.1016/j.mehy.2011.04.021. View

Jensen M, Karoly P . Motivation and expectancy factors in symptom perception: a laboratory study of the placebo effect. Psychosom Med. 1991; 53(2):144-52. DOI: 10.1097/00006842-199103000-00004. View

Gao X, Zhang S, Zhu B, Zhang H . Investigation of specificity of auricular acupuncture points in regulation of autonomic function in anesthetized rats. Auton Neurosci. 2007; 138(1-2):50-6. DOI: 10.1016/j.autneu.2007.10.003. View

Stefan H, Kreiselmeyer G, Kerling F, Kurzbuch K, Rauch C, Heers M . Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia. 2012; 53(7):e115-8. DOI: 10.1111/j.1528-1167.2012.03492.x. View

Sperling W, Reulbach U, Kornhuber J . Clinical benefits and cost effectiveness of vagus nerve stimulation in a long-term treatment of patients with major depression. Pharmacopsychiatry. 2009; 42(3):85-8. DOI: 10.1055/s-0028-1103294. View

Henry T . Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002; 59(6 Suppl 4):S3-14. DOI: 10.1212/wnl.59.6_suppl_4.s3. View

Rush A, Sackeim H, Marangell L, George M, Brannan S, Davis S . Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005; 58(5):355-63. DOI: 10.1016/j.biopsych.2005.05.024. View

Kaptchuk T . The placebo effect in alternative medicine: can the performance of a healing ritual have clinical significance?. Ann Intern Med. 2002; 136(11):817-25. DOI: 10.7326/0003-4819-136-11-200206040-00011. View

Henry T, Bakay R, Votaw J, Pennell P, Epstein C, Faber T . Brain blood flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: I. Acute effects at high and low levels of stimulation. Epilepsia. 1998; 39(9):983-90. DOI: 10.1111/j.1528-1157.1998.tb01448.x. View

10.

Henry T, Bakay R, Pennell P, Epstein C, Votaw J . Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. prolonged effects at high and low levels of stimulation. Epilepsia. 2004; 45(9):1064-70. DOI: 10.1111/j.0013-9580.2004.03104.x. View

11.

Peuker E, Filler T . The nerve supply of the human auricle. Clin Anat. 2002; 15(1):35-7. DOI: 10.1002/ca.1089. View

12.

Kraus T, Hosl K, Kiess O, Schanze A, Kornhuber J, Forster C . BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation. J Neural Transm (Vienna). 2007; 114(11):1485-93. DOI: 10.1007/s00702-007-0755-z. View

13.

Zobel A, Joe A, Freymann N, Clusmann H, Schramm J, Reinhardt M . Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Res. 2005; 139(3):165-79. DOI: 10.1016/j.pscychresns.2005.02.010. View

14.

Michaud C, Murray C, Bloom B . Burden of disease--implications for future research. JAMA. 2001; 285(5):535-9. DOI: 10.1001/jama.285.5.535. View

15.

Ventureyra E . Transcutaneous vagus nerve stimulation for partial onset seizure therapy. A new concept. Childs Nerv Syst. 2000; 16(2):101-2. DOI: 10.1007/s003810050021. View

16.

Mohr P, Rodriguez M, Slavickova A, Hanka J . The application of vagus nerve stimulation and deep brain stimulation in depression. Neuropsychobiology. 2011; 64(3):170-81. DOI: 10.1159/000325225. View

17.

Rush A, Marangell L, Sackeim H, George M, Brannan S, Davis S . Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005; 58(5):347-54. DOI: 10.1016/j.biopsych.2005.05.025. View

18.

Nemeroff C, Mayberg H, Krahl S, McNamara J, Frazer A, Henry T . VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology. 2006; 31(7):1345-55. DOI: 10.1038/sj.npp.1301082. View

19.

Kalauokalani D, Cherkin D, Sherman K, Koepsell T, Deyo R . Lessons from a trial of acupuncture and massage for low back pain: patient expectations and treatment effects. Spine (Phila Pa 1976). 2001; 26(13):1418-24. DOI: 10.1097/00007632-200107010-00005. View

20.

Daban C, Martinez-Aran A, Cruz N, Vieta E . Safety and efficacy of Vagus Nerve Stimulation in treatment-resistant depression. A systematic review. J Affect Disord. 2008; 110(1-2):1-15. DOI: 10.1016/j.jad.2008.02.012. View