{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:06:49Z","timestamp":1791986809523,"version":"4.4.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T00:00:00Z","timestamp":1615420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Tinnitus is a phantom sensation of sound, which can have a negative impact on quality of life of those affected. No curative treatments are currently known. Neuromodulation by vagus nerve stimulation has emerged as a new treatment option for tinnitus, though till date the effectiveness remains unclear. Therefore, we aim to review the effect of vagus nerve stimulation on tinnitus distress and tinnitus symptom severity in patients with chronic tinnitus.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>We searched Pubmed, Embase and the Cochrane Library systematically for RCTs, observational studies and case studies on the effect of VNS treatment for tinnitus on October 29, 2019. Studies including adult patients with subjective tinnitus, comparing transcutaneous or implantable VNS to placebo or no treatment or before and after application of VNS treatment on tinnitus distress and tinnitus symptom severity measured with a validated questionnaire were eligible. The risk of bias was assessed with the appropriate tool for each type of study.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>Our search identified 9 primary studies of which 2 RCTs, 5 cohort studies and 2 case series or reports. 5 studies used transcutaneous VNS treatment and 4 used implanted VNS treatment. 6 studies combined VNS treatment with sound therapy. There was a serious risk of bias in all studies, especially on confounding. Most studies reported a small decrease in tinnitus distress or tinnitus symptom severity.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Due to methodological limitations and low reporting quality of the included studies, the effect of VNS on tinnitus remains unclear. To draw conclusions for which patient population and to what extent (t)VNS is beneficial in the treatment of tinnitus, a randomised controlled trial should be considered.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0247221","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T18:50:01Z","timestamp":1615488601000},"page":"e0247221","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":49,"title":["Tinnitus treatment by vagus nerve stimulation: A systematic review"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5154-7178","authenticated-orcid":true,"given":"I.","family":"Stegeman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9408-5433","authenticated-orcid":true,"given":"H. M.","family":"Velde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7845-6196","authenticated-orcid":true,"given":"P. A. J. T.","family":"Robe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. J.","family":"Stokroos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. L.","family":"Smit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,3,11]]},"reference":[{"key":"pone.0247221.ref001","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1155\/2015\/608437","article-title":"Pathology of tinnitus and hyperacusis-clinical implications","volume":"2015","author":"AR Moller","year":"2015","journal-title":"Biomed Res Int"},{"issue":"August","key":"pone.0247221.ref002","first-page":"1","article-title":"Why Is There No Cure for Tinnitus?","volume":"13","author":"DJ McFerran","year":"2019","journal-title":"Front Neurosci"},{"issue":"7","key":"pone.0247221.ref003","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3109\/15622975.2011.575178","article-title":"Tinnitus and depression","volume":"12","author":"B Langguth","year":"2011","journal-title":"World J Biol Psychiatry [Internet]"},{"issue":"1","key":"pone.0247221.ref004","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuron.2010.12.002","article-title":"Dysregulation of Limbic and Auditory Networks in Tinnitus","volume":"69","author":"AM Leaver","year":"2011","journal-title":"Neuron [Internet]"},{"key":"pone.0247221.ref005","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jpsychores.2016.03.001","article-title":"Insomnia in patients with chronic tinnitus: Cognitive and emotional distress as moderator variables","volume":"83","author":"T Cr\u00f6nlein","year":"2016","journal-title":"J Psychosom Res [Internet]"},{"issue":"3","key":"pone.0247221.ref006","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1177\/1084713808319941","article-title":"The Role of Audiologic Evaluation in Progressive Audiologic Tinnitus Management","volume":"12","author":"J a. Henry","year":"2008","journal-title":"Trends Amplif"},{"key":"pone.0247221.ref007","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.heares.2012.10.001","article-title":"Directing neural plasticity to understand and treat tinnitus","volume":"295","author":"ND Engineer","year":"2013","journal-title":"Hear Res [Internet]"},{"issue":"January-February","key":"pone.0247221.ref008","article-title":"The neuroscience of trust","volume":"2017","author":"E JJ","year":"2017","journal-title":"Harv Bus Rev"},{"key":"pone.0247221.ref009","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.neuroscience.2011.05.024","article-title":"Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors","volume":"189","author":"JA Nichols","year":"2011","journal-title":"Neuroscience [Internet]"},{"issue":"11","key":"pone.0247221.ref010","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1007\/s00702-007-0755-z","article-title":"BOLD fMRI deactivation of limbic and temporal brain structures and mood enhancing effect by transcutaneous vagus nerve stimulation","volume":"114","author":"T Kraus","year":"2007","journal-title":"J Neural Transm"},{"issue":"1\u20132","key":"pone.0247221.ref011","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.heares.2007.01.005","article-title":"Experience dependent plasticity alters cortical synchronization","volume":"229","author":"MP Kilgard","year":"2007","journal-title":"Hear Res"},{"issue":"7","key":"pone.0247221.ref012","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement","volume":"6","author":"D Moher","year":"2009","journal-title":"PLoS Med"},{"key":"pone.0247221.ref013","first-page":"4","article-title":"ROBINS-I: A tool for assessing risk of bias in non-randomised studies of interventions","volume":"355","author":"JA Sterne","year":"2016","journal-title":"BMJ"},{"key":"pone.0247221.ref014","unstructured":"Cochrane handbook [Internet]. [cited 2016 Oct 31]. Available from: http:\/\/handbook.cochrane.org\/chapter_8\/8_assessing_risk_of_bias_in_included_studies.htm"},{"issue":"1","key":"pone.0247221.ref015","doi-asserted-by":"crossref","first-page":"17345","DOI":"10.1038\/s41598-017-17750-y","article-title":"Pairing sound with vagus nerve stimulation modulates cortical synchrony and phase coherence in tinnitus: An exploratory retrospective study","volume":"7","author":"S Vanneste","year":"2017","journal-title":"Sci Rep"},{"issue":"2","key":"pone.0247221.ref016","doi-asserted-by":"crossref","first-page":"267","DOI":"10.5152\/iao.2018.3977","article-title":"Characteristics of stimulus intensity in transcutaneous vagus nerve stimulation for chronic tinnitus","volume":"14","author":"WC Suk","year":"2018","journal-title":"J Int Adv Otol.Aug"},{"issue":"3","key":"pone.0247221.ref017","doi-asserted-by":"crossref","first-page":"159","DOI":"10.7874\/jao.2015.19.3.159","article-title":"Feasibility and Safety of Transcutaneous Vagus Nerve Stimulation Paired with Notched Music Therapy for the Treatment of Chronic Tinnitus","volume":"19","author":"HJ Shim","year":"2015","journal-title":"J Audiol Otol"},{"issue":"2","key":"pone.0247221.ref018","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S1003-5257(14)60022-2","article-title":"Treatment of tinnitus with electrical stimulation on acupoint in the distribution area of ear vagus nerve combining with sound masking: randomized controlled trial","volume":"24","author":"Z Mei","year":"2014","journal-title":"World J Acupunct\u2014Moxibustion"},{"issue":"5","key":"pone.0247221.ref019","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.brs.2014.05.003","article-title":"Brain Stimulation Feasibility, Safety and Ef fi cacy of Transcutaneous Vagus Nerve Stimulation in Chronic Tinnitus: An Open Pilot Study","volume":"7","author":"PM Kreuzer","year":"2014","journal-title":"Brain Stimul"},{"issue":"4","key":"pone.0247221.ref020","doi-asserted-by":"crossref","first-page":"378","DOI":"10.3109\/00016489.2012.750736","volume":"133","author":"J Lehtim\u00e4ki","year":"2013","journal-title":"Acta Otolaryngol"},{"issue":"5","key":"pone.0247221.ref021","first-page":"599","article-title":"Tinnitus perception in patients after vagal nerve stimulator implantation for epilepsy","volume":"39","author":"H Wichova","year":"2018","journal-title":"Am J Otolaryngol\u2014Head Neck Med Surg"},{"issue":"1","key":"pone.0247221.ref022","doi-asserted-by":"crossref","first-page":"11960","DOI":"10.1038\/s41598-017-12178-w","article-title":"Vagus Nerve Stimulation Paired with Tones for the Treatment of Tinnitus: A Prospective Randomized Double-blind Controlled Pilot Study in Humans","volume":"7","author":"R Tyler","year":"2017","journal-title":"Sci Rep"},{"key":"pone.0247221.ref023","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1097\/MAO.0000000000000704","article-title":"Placebo-controlled vagus nerve stimulation paired with tones in a patient with refractory tinnitus: a case report","volume":"36","author":"D De Ridder","year":"2015","journal-title":"Otology & neurotology: official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology"},{"issue":"2","key":"pone.0247221.ref024","first-page":"170","volume":"17","author":"D De Ridder","year":"2014","journal-title":"Feb"},{"issue":"5","key":"pone.0247221.ref025","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.brs.2014.05.003","article-title":"Feasibility, safety and efficacy of transcutaneous vagus nerve stimulation in chronic tinnitus: An open pilot study","volume":"7","author":"PM Kreuzer","year":"2014","journal-title":"Brain Stimul [Internet]"},{"issue":"6","key":"pone.0247221.ref026","article-title":"Neuromodulation (desynchronisation) for tinnitus in adults","volume":"2015","author":"DJ Hoare","year":"2015","journal-title":"Cochrane Database Syst Rev"},{"issue":"1","key":"pone.0247221.ref027","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.neuron.2010.12.002","article-title":"Dysregulation of Limbic and Auditory Networks in Tinnitus","volume":"69","author":"AM Leaver","year":"2011","journal-title":"Neuron"},{"key":"pone.0247221.ref028","doi-asserted-by":"crossref","first-page":"152156","DOI":"10.1016\/j.comppsych.2019.152156","article-title":"Vagus nerve stimulation (VNS) therapy in patients with treatment resistant depression: A systematic review and meta-analysis","volume":"98","author":"JM Bottomley","year":"2020","journal-title":"Compr Psychiatry"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247221","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T18:50:32Z","timestamp":1615488632000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0247221"}},"subtitle":[],"editor":[{"given":"Sarah","family":"Michiels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,3,11]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,3,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0247221","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,11]]}}}