Transcutaneous Vagus Nerve Stimulation (taVNS) for Major Depressive Disorder: An Open Label Proof-of-Concept Trial

Despite recent advances in pharmacological treatments, Major Depressive Disorder (MDD) remains an incapacitating psychiatric condition with increasing prevalence and economic burden [ [1] Nock M.K. Kessler R.C. Prevalence of and risk factors for suicide attempts versus suicide gestures: analysis of the National Comorbidity Survey. J Abnorm Psychol. 2006; 115: 616-623 Crossref PubMed Scopus (445) Google Scholar ]. New therapeutical strategies such as vagus nerve stimulation (VNS) are being studied [ [2] George M.S. Brain stimulation, as a field, continues to evolve and expand. From the Editor-in-Chief's desk. Brain Stimul. 2010; 3: 63-64 Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar ]. Different brain sites can be modulated by using electrical currents, which can theoretically restore balance to impaired circuits leading to clinical amelioration of symptoms. VNS involves the direct stimulation of the vagus nerve leading to further modulation of impaired brain areas related to psychiatric disorders [ 3 George M.S. Ward Jr, H.E. Ninan P.T. Pollack M. Nahas Z. Anderson B. et al. A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul. 2008; 1: 112-121 Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar , 4 George M.S. Aston-Jones G. Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology. 2010; 35: 301-316 Crossref PubMed Scopus (246) Google Scholar ]. Target stimulated areas include solitary tract nucleus, dorsal raphe, locus coeruleus, parabrachial area, amygdala, nucleus accumbent, hippocampus and the dorsolateral prefrontal cortex (DLPFC) [ [5] Frangos E. Ellrich J. Komisaruk B.R. Non-invasive access to the vagus nerve central projections via electrical stimulation of the external ear: fMRI evidence in humans. Brain Stimul. 2015; 8: 624-636 Abstract Full Text Full Text PDF PubMed Scopus (337) Google Scholar ]. Non-invasive VNS stimulation protocols have been assessed with promising results [ [6] Hein E. Nowak M. Kiess O. Biermann T. Bayerlein K. Kornhuber J. et al. Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm. 2013; 120: 821-827 Crossref PubMed Scopus (138) Google Scholar ]. In fact, our group and others have recently proposed a hypothetically safer non-invasive approach for transcutaneously stimulating the vagus nerve in the ear, transcutaneous auricular VNS (taVNS) [ [7] Trevizol A. Barros M.D. Liquidato B. Cordeiro Q. Shiozawa P. Vagus nerve stimulation in neuropsychiatry: targeting anatomy-based stimulation sites. Epilepsy Behav. 2015; 51: 18 Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar ]. There are also methods for non-invasively stimulating the vagus nerve in the neck, or cervical region, called transcutaneous cervical VNS (tcVNS). We undertook this proof-of-concept study to evaluate both the safety and potential clinical efficacy of this new experimental protocol with taVNS for treating patients with MDD.