vagus nerve stimulation

VNS is used to treat drug-resistant epilepsy.{{cite journal | vauthors = Panebianco M, Rigby A, Marson AG | title = Vagus nerve stimulation for focal seizures | journal = The Cochrane Database of Systematic Reviews | volume = 2022 | issue = 7 | pages = CD002896 | date = July 2022 | pmid = 35833911 | pmc = 9281624 | doi = 10.1002/14651858.CD002896.pub3 }} For refractive epilepsy, cervical VNS on the left side is FDA-approved.{{cite journal | vauthors = Howland RH | title = Vagus Nerve Stimulation | journal = Current Behavioral Neuroscience Reports | volume = 1 | issue = 2 | pages = 64–73 | date = June 2014 | pmid = 24834378 | pmc = 4017164 | doi = 10.1007/s40473-014-0010-5 }}{{cite journal | vauthors = Yuan H, Silberstein SD | title = Vagus Nerve and Vagus Nerve Stimulation, a Comprehensive Review: Part II | journal = Headache | volume = 56 | issue = 2 | pages = 259–266 | date = February 2016 | pmid = 26381725 | doi = 10.1111/head.12650 }}

In the United States, VNS is approved as adjunctive therapy for those 4 years of age or older with refractory focal onset seizures. In the European Union, VNS is approved as an adjunctive therapy for patients with either generalized or focal onset seizures without any age restrictions.{{cite journal | vauthors = Wheless JW, Gienapp AJ, Ryvlin P | title = Vagus nerve stimulation (VNS) therapy update | journal = Epilepsy & Behavior | volume = 88S | pages = 2–10 | date = November 2018 | pmid = 30017839 | doi = 10.1016/j.yebeh.2018.06.032 | s2cid = 51679627 }} It is recommended that VNS is only pursued following an adequate trial of at least 2 appropriately chosen anti-seizure medications and that the patient is ineligible for epilepsy surgery.{{cite journal | vauthors = Morris GL, Gloss D, Buchhalter J, Mack KJ, Nickels K, Harden C | title = Evidence-based guideline update: vagus nerve stimulation for the treatment of epilepsy: report of the Guideline Development Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 81 | issue = 16 | pages = 1453–1459 | date = October 2013 | pmid = 23986299 | pmc = 3806910 | doi = 10.1212/wnl.0b013e3182a393d1 }} This is because epilepsy surgery is associated with a higher probability of resulting in seizure freedom.{{cite journal | vauthors = Fisher RS, Handforth A | title = Reassessment: vagus nerve stimulation for epilepsy: a report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology | journal = Neurology | volume = 53 | issue = 4 | pages = 666–669 | date = September 1999 | pmid = 10489023 | doi = 10.1212/wnl.53.4.666 | s2cid = 20845641 | doi-access = free }} Patients who have poor adherence or tolerance of anti-seizure medications may be good candidates for VNS.{{cite journal | vauthors = Helmers SL, Duh MS, Guérin A, Sarda SP, Samuelson TM, Bunker MT, Olin BD, Jackson SD, Faught E | title = Clinical and economic impact of vagus nerve stimulation therapy in patients with drug-resistant epilepsy | journal = Epilepsy & Behavior | volume = 22 | issue = 2 | pages = 370–375 | date = October 2011 | pmid = 21872534 | doi = 10.1016/j.yebeh.2011.07.020 | s2cid = 7869407 }}

VNS may provide benefit for particular epilepsy syndromes and seizure types such as Lennox-Gastaut syndrome, tuberous sclerosis complex related epilepsy, refractory absence seizures and atonic seizures.{{cite journal | vauthors = Grioni D, Landi A | title = Does Vagal Nerve Stimulation Treat Drug-Resistant Epilepsy in Patients with Tuberous Sclerosis Complex? | journal = World Neurosurgery | volume = 121 | pages = 251–253 | date = January 2019 | pmid = 30347295 | doi = 10.1016/j.wneu.2018.10.077 | s2cid = 53034756 }}{{cite journal | vauthors = Braakman HM, Creemers J, Hilkman DM, Klinkenberg S, Koudijs SM, Debeij-van Hall M, Cornips EM | title = Improved seizure control and regaining cognitive milestones after vagus nerve stimulation revision surgery in Lennox-Gastaut syndrome | journal = Epilepsy & Behavior Case Reports | volume = 10 | pages = 111–113 | date = 2018 | pmid = 30364578 | pmc = 6197149 | doi = 10.1016/j.ebcr.2018.08.002 }}{{cite journal | vauthors = Arya R, Greiner HM, Lewis A, Mangano FT, Gonsalves C, Holland KD, Glauser TA | title = Vagus nerve stimulation for medically refractory absence epilepsy | journal = Seizure | volume = 22 | issue = 4 | pages = 267–270 | date = May 2013 | pmid = 23391567 | doi = 10.1016/j.seizure.2013.01.008 | s2cid = 14917920 | doi-access = free }}{{cite journal | vauthors = Rolston JD, Englot DJ, Wang DD, Garcia PA, Chang EF | title = Corpus callosotomy versus vagus nerve stimulation for atonic seizures and drop attacks: A systematic review | journal = Epilepsy & Behavior | volume = 51 | pages = 13–17 | date = October 2015 | pmid = 26247311 | pmc = 5261864 | doi = 10.1016/j.yebeh.2015.06.001 }} There are also reports of VNS being successfully utilized in patients with refractory and super-refractory status epilepticus.{{cite journal | vauthors = Dibué-Adjei M, Brigo F, Yamamoto T, Vonck K, Trinka E | title = Vagus nerve stimulation in refractory and super-refractory status epilepticus - A systematic review | journal = Brain Stimulation | volume = 12 | issue = 5 | pages = 1101–1110 | date = September 2019 | pmid = 31126871 | doi = 10.1016/j.brs.2019.05.011 | s2cid = 153310356 | doi-access = free }}

The UK National Institute for Health and Care Excellence (NICE) in the UK recommends VNS for cluster headaches.{{Cite web | url=https://www.nice.org.uk/guidance/mtg46/documents/final-scope | title=The Nurosym/Parasym | website=www.nice.org.uk}} In 2017 the FDA approved the non-invasive gammaCore VNS system for treatment of episodic cluster headache and expanded its approved usage to acute treatment of pain associated with migraine.{{Cite web |title=gammaCore® Receives FDA Clearance for the Acute Treatment of Pain Associated with Migraine Headache in Adult Patients |url=https://www.electrocore.com/news/gammacore-receives-fda-clearance-acute-treatment-pain-associated-migraine-headache-adult-patients/ |access-date=2025-02-25 |website=electroCore |language=en-US}} Two randomized, double-blind, and sham-controlled studies have administered nVNS to patients with episodic cluster headaches; both demonstrated a significant effect in reducing acute cluster attacks.{{Cite journal |last1=Peng |first1=Kuan-Po |last2=Burish |first2=Mark J. |date=2023-08-01 |title=Management of cluster headache: Treatments and their mechanisms |journal=Cephalalgia |language=EN |volume=43 |issue=8 |pages=03331024231196808 |doi=10.1177/03331024231196808 |issn=0333-1024|doi-access=free |pmid=37652457 }}{{Cite journal |last1=Silberstein |first1=Stephen D. |last2=Mechtler |first2=Laszlo L. |last3=Kudrow |first3=David B. |last4=Calhoun |first4=Anne H. |last5=McClure |first5=Candace |last6=Saper |first6=Joel R. |last7=Liebler |first7=Eric J. |last8=Rubenstein Engel |first8=Emily |last9=Tepper |first9=Stewart J. |date=2016 |title=Non–Invasive Vagus Nerve Stimulation for the ACute Treatment of Cluster Headache: Findings From the Randomized, Double-Blind, Sham-Controlled ACT1 Study |journal=Headache: The Journal of Head and Face Pain |language=en |volume=56 |issue=8 |pages=1317–1332 |doi=10.1111/head.12896 |issn=1526-4610 |pmc=5113831 |pmid=27593728}}{{Cite journal |last1=Goadsby |first1=Peter J |last2=de Coo |first2=Ilse F |last3=Silver |first3=Nicholas |last4=Tyagi |first4=Alok |last5=Ahmed |first5=Fayyaz |last6=Gaul |first6=Charly |last7=Jensen |first7=Rigmor H |last8=Diener |first8=Hans-Christoph |last9=Solbach |first9=Kasia |last10=Straube |first10=Andreas |last11=Liebler |first11=Eric |last12=Marin |first12=Juana CA |last13=Ferrari |first13=Michel D |date=2018-04-01 |title=Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: A randomized, double-blind, sham-controlled ACT2 study |journal=Cephalalgia |language=EN |volume=38 |issue=5 |pages=959–969 |doi=10.1177/0333102417744362 |issn=0333-1024 |pmc=5896689 |pmid=29231763}}

VNS is used to treat treatment-resistant major depressive disorder (TR-MDD).

{{cite journal | vauthors = Carreno FR, Frazer A | title = Vagal Nerve Stimulation for Treatment-Resistant Depression | journal = Neurotherapeutics | volume = 14 | issue = 3 | pages = 716–727 | date = July 2017 | pmid = 28585221 | pmc = 5509631 | doi = 10.1007/s13311-017-0537-8 }} For treatment resistant depression, cervical VNS on the left side is FDA-approved. The UK NICE guidance (from 2020) stated that "Evidence on its efficacy is limited in quality." and encouraged further research studies "in the form of randomised controlled trials with a placebo or sham stimulation arm."{{cite web | url=https://www.nice.org.uk/guidance/ipg679/chapter/1-Recommendations | title=1 Recommendations | Implanted vagus nerve stimulation for treatment-resistant depression | Guidance | NICE | date=12 August 2020 }}

VNS has been used to treat chronic pain due to various causes, although the mechanisms for this relief has yet to be determined.{{cite journal | vauthors = Shao P, Li H, Jiang J, Guan Y, Chen X, Wang Y | title = Role of Vagus Nerve Stimulation in the Treatment of Chronic Pain | journal = Neuroimmunomodulation | volume = 30 | issue = 1 | pages = 167–183 | date = 2023 | pmid = 37369181 | pmc = 10614462 | doi = 10.1159/000531626 }}

VNS has shown to be of value in treatment of heart failure.{{cite journal | vauthors = Capilupi MJ, Kerath SM, Becker LB | title = Vagus Nerve Stimulation and the Cardiovascular System | journal = Cold Spring Harbor Perspectives in Medicine | volume = 10 | issue = 2 | pages = a034173 | date = February 2020 | pmid = 31109966 | pmc = 6996447 | doi = 10.1101/cshperspect.a034173 }} One study did not show reduction in death rates, but did show improvement in six minute hall walk duration and quality of life.

Animal studies have shown the capacity of low-level VNS to reduce inducibility of atrial fibrillation. This effect has been proposed to be due to inhibition of the ganglionated plexi.

VNS can be used either invasively or non-invasively to treat ischemic stroke.{{cite journal | vauthors = Andalib S, Divani AA, Ayata C, Baig S, Arsava EM, Topcuoglu MA, Cáceres EL, Parikh V, Desai MJ, Majid A, Girolami S, Di Napoli M | title = Vagus Nerve Stimulation in Ischemic Stroke | journal = Current Neurology and Neuroscience Reports | volume = 23 | issue = 12 | pages = 947–962 | date = December 2023 | pmid = 38008851 | pmc = 10841711 | doi = 10.1007/s11910-023-01323-w }} Invasive VNS can only be applied invasively (by surgery), but non-invasive VNS can be applied in acute settings.

In 2021 the U.S. Food and Drug Administration approved the MicroTransponder Vivistim Paired VNS System (Vivistim System) to treat moderate to severe upper extremity motor deficits associated with chronic ischemic stroke.{{cite web | url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-its-kind-stroke-rehabilitation-system#:~:text=%E2%80%9CToday%27s%20approval%20of%20the%20Vivistim,limbs%20due%20to%20ischemic%20stroke.%E2%80%9D | title=FDA Approves First-of-Its-Kind Stroke Rehabilitation System | website=Food and Drug Administration | date=31 August 2021 }}{{cite journal | vauthors = Liu CY, Russin J, Adelson DP, Jenkins A, Hilmi O, Brown B, Lega B, Whitworth T, Bhattacharyya D, Schwartz TH, Krishna V, Williams Z, Uff C, Willie J, Hoffman C, Vandergrift WA, Achrol AS, Ali R, Konrad P, Edmonds J, Kim D, Bhatt P, Tarver BW, Pierce D, Jain R, Burress C, Casavant R, Prudente CN, Engineer ND | title = Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial | journal = Journal of Clinical Neuroscience | volume = 105 | pages = 122–128 | date = November 2022 | pmid = 36182812 | doi = 10.1016/j.jocn.2022.09.013 }}

A meta-analysis of 74 clinical studies with 3321 patients found that VNS produced an average 51% reduction in seizures after 1 year of therapy.{{cite journal | vauthors = Englot DJ, Chang EF, Auguste KI | title = Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response | journal = Journal of Neurosurgery | volume = 115 | issue = 6 | pages = 1248–1255 | date = December 2011 | pmid = 21838505 | doi = 10.3171/2011.7.JNS11977 }} Approximately 50% of patients had an equal to or greater than 50% reduction in seizures at the time of last follow-up. Long-term studies have shown that response to VNS increases over time. For instance, a study that followed 74 patients for 10–17 years found a seizure frequency reduction of 50-90% in 38.4%, 51.4%, 63.6% and 77.8% of patients at 1-, 2-, 10- and 17-years following implantation, respectively.{{cite journal | vauthors = Chrastina J, Novák Z, Zeman T, Kočvarová J, Pail M, Doležalová I, Jarkovský J, Brázdil M | title = Single-center long-term results of vagus nerve stimulation for epilepsy: A 10-17 year follow-up study | journal = Seizure | volume = 59 | pages = 41–47 | date = July 2018 | pmid = 29738985 | doi = 10.1016/j.seizure.2018.04.022 | s2cid = 13700901 | doi-access = free }} Approximately, 8% have total resolution of seizures.{{cite journal | vauthors = Englot DJ, Rolston JD, Wright CW, Hassnain KH, Chang EF | title = Rates and Predictors of Seizure Freedom With Vagus Nerve Stimulation for Intractable Epilepsy | journal = Neurosurgery | volume = 79 | issue = 3 | pages = 345–353 | date = September 2016 | pmid = 26645965 | pmc = 4884552 | doi = 10.1227/NEU.0000000000001165 }} VNS has also been shown to reduce rates of sudden unexpected death in epilepsy (SUDEP) and to improve quality of life metrics.{{cite journal | vauthors = Englot DJ, Hassnain KH, Rolston JD, Harward SC, Sinha SR, Haglund MM | title = Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data | journal = Epilepsy & Behavior | volume = 66 | pages = 4–9 | date = January 2017 | pmid = 27974275 | pmc = 5258831 | doi = 10.1016/j.yebeh.2016.10.005 }}{{cite journal | vauthors = Ryvlin P, So EL, Gordon CM, Hesdorffer DC, Sperling MR, Devinsky O, Bunker MT, Olin B, Friedman D | title = Long-term surveillance of SUDEP in drug-resistant epilepsy patients treated with VNS therapy | journal = Epilepsia | volume = 59 | issue = 3 | pages = 562–572 | date = March 2018 | pmid = 29336017 | doi = 10.1111/epi.14002 | s2cid = 3782079 | doi-access = free }} A number of predictors of a favorable clinical response have been identified including epilepsy onset > 12 years of age, generalized epilepsy type, non-lesional epilepsy, posttraumatic epilepsy and those who have less than a 10-year history of seizures.{{cite journal | vauthors = Englot DJ, Rolston JD, Wang DD, Hassnain KH, Gordon CM, Chang EF | title = Efficacy of vagus nerve stimulation in posttraumatic versus nontraumatic epilepsy | journal = Journal of Neurosurgery | volume = 117 | issue = 5 | pages = 970–977 | date = November 2012 | pmid = 22978542 | doi = 10.3171/2012.8.jns122 | doi-access = free }}

Long-term cognitive outcomes are at least stable following VNS.{{cite journal | vauthors = Lam J, Williams M, Ashla M, Lee DJ | title = Cognitive outcomes following vagus nerve stimulation, responsive neurostimulation and deep brain stimulation for epilepsy: A systematic review | journal = Epilepsy Research | volume = 172 | pages = 106591 | date = May 2021 | pmid = 33711711 | doi = 10.1016/j.eplepsyres.2021.106591 | s2cid = 231956548 }}

One study of children with epilepsy found that a post hoc analysis revealed a dose–response correlation for VNS.{{cite journal | vauthors = Orosz I, McCormick D, Zamponi N, Varadkar S, Feucht M, Parain D, Griens R, Vallée L, Boon P, Rittey C, Jayewardene AK, Bunker M, Arzimanoglou A, Lagae L | title = Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children | journal = Epilepsia | volume = 55 | issue = 10 | pages = 1576–1584 | date = October 2014 | pmid = 25231724 | doi = 10.1111/epi.12762 | s2cid = 25790247 | doi-access = free }}

A 2022 narrative review concluded that VNS is an effective and well-tolerated therapy for chronic and treatment-resistant depression. Importantly, the review also noted that the therapeutic effect of VNS in this context may take 3–12 months to materialize but may be persistent long-term.{{cite journal | vauthors = Reif-Leonhard C, Reif A, Baune BT, Kavakbasi E | title = [Vagus nerve stimulation for difficult to treat depression] | journal = Der Nervenarzt | volume = 93 | issue = 9 | pages = 921–930 | date = September 2022 | pmid = 35380222 | pmc = 9452433 | doi = 10.1007/s00115-022-01282-6 | doi-access = free }}{{cite news | vauthors = Kron T |title=Vagus Nerve Stimulation: A Little-Known Option for Depression |url=https://www.medscape.com/viewarticle/973508 |work=Medscape |date=5 May 2022 }} One study of only 10 weeks found no effect.{{cite journal | vauthors = Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG | title = Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial | journal = Biological Psychiatry | volume = 58 | issue = 5 | pages = 347–354 | date = September 2005 | pmid = 16139580 | doi = 10.1016/j.biopsych.2005.05.025 }}

A 2020 review concluded "Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response.{{cite journal | vauthors = Assenza G, Tombini M, Lanzone J, Ricci L, Di Lazzaro V, Casciato S, Morano A, Giallonardo AT, Di Bonaventura C, Beghi E, Ferlazzo E, Gasparini S, Giuliano L, Pisani F, Benna P, Bisulli F, De Falco FA, Franceschetti S, La Neve A, Meletti S, Mostacci B, Sartucci F, Striano P, Villani F, Aguglia U, Avanzini G, Belcastro V, Bianchi A, Cianci V, Labate A, Magaudda A, Michelucci R, Verri A, Zaccara G, Pizza V, Tinuper P, Di Gennaro G | title = Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review | journal = Neurological Sciences | volume = 41 | issue = 11 | pages = 3075–3084 | date = November 2020 | pmid = 32524324 | doi = 10.1007/s10072-020-04479-2 | s2cid = 219567684 }}

In one study higher electrical dose parameters were associated with response durability.{{cite journal | vauthors = Aaronson ST, Carpenter LL, Conway CR, Reimherr FW, Lisanby SH, Schwartz TL, Moreno FA, Dunner DL, Lesem MD, Thompson PM, Husain M, Vine CJ, Banov MD, Bernstein LP, Lehman RB, Brannon GE, Keepers GA, O'Reardon JP, Rudolph RL, Bunker M | title = Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects | journal = Brain Stimulation | volume = 6 | issue = 4 | pages = 631–640 | date = July 2013 | pmid = 23122916 | doi = 10.1016/j.brs.2012.09.013 }}

VNS may have positive well-being, mood and quality of life effects.{{cite book |doi=10.1016/B978-0-323-91702-5.00004-9 |chapter=Quality of life, neurocognitive outcomes, and mood effects with neurostimulation devices |title=Neurostimulation for Epilepsy |date=2023 |pages=229–244 |isbn=978-0-323-91702-5 | vauthors = Arredondo K, Patel AD }}{{cite journal | vauthors = Schachter SC | title = Vagus nerve stimulation: mood and cognitive effects | journal = Epilepsy & Behavior | volume = 5 Suppl 1 | pages = S56–S59 | date = February 2004 | pmid = 14725847 | doi = 10.1016/j.yebeh.2003.11.007 }}

Studies have found improvements in standard patient-reported mood assessment scales in adult patients with epilepsy after using VNS, and some have found no association between mood change and reduction in seizure frequency.{{cite journal | vauthors = Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE | title = Vagus nerve stimulation is associated with mood improvements in epilepsy patients | journal = Epilepsy Research | volume = 42 | issue = 2–3 | pages = 203–210 | date = December 2000 | pmid = 11074193 | doi = 10.1016/s0920-1211(00)00181-9 }}{{cite journal | vauthors = Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR | title = A Pilot Study of Mood in Epilepsy Patients Treated with Vagus Nerve Stimulation | journal = Epilepsy & Behavior | volume = 1 | issue = 2 | pages = 93–99 | date = April 2000 | pmid = 12609137 | doi = 10.1006/ebeh.2000.0046 }}

Another study of epilepsy patients measured a general mood improvement, and suggested that VNS may improve unspecific states of indisposition and dysphoria.{{cite journal | vauthors = Hoppe C, Helmstaedter C, Scherrmann J, Elger CE | title = Self-Reported Mood Changes following 6 Months of Vagus Nerve Stimulation in Epilepsy Patients | journal = Epilepsy & Behavior | volume = 2 | issue = 4 | pages = 335–342 | date = August 2001 | pmid = 12609210 | doi = 10.1006/ebeh.2001.0194 | s2cid = 22552070 }}

Patients with comorbid depression have been found to have mood improvements with VNS therapy.{{cite journal | vauthors = Fan JJ, Shan W, Wu JP, Wang Q | title = Research progress of vagus nerve stimulation in the treatment of epilepsy | journal = CNS Neuroscience & Therapeutics | volume = 25 | issue = 11 | pages = 1222–1228 | date = November 2019 | pmid = 31429206 | pmc = 6834923 | doi = 10.1111/cns.13209 }}

Quality of life (QOL) improvement was also associated with VNS use.{{cite journal | vauthors = Ryvlin P, Gilliam FG, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, Stefan H, Boon P, Sadler M, Benna P, Raman P, Perucca E | title = The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial | journal = Epilepsia | volume = 55 | issue = 6 | pages = 893–900 | date = June 2014 | pmid = 24754318 | pmc = 4283995 | doi = 10.1111/epi.12611 }} One study of children with epilepsy found that better quality of life outcomes after VNS implantation were strongly associated with shorter duration of preoperative seizures and implantation at a young age.{{cite journal | vauthors = Knorr C, Greuter L, Constantini S, Fried I, Kremer U, Datta AN, Guzman R, Soleman J | title = Subgroup analysis of seizure and cognitive outcome after vagal nerve stimulator implantation in children | journal = Child's Nervous System | volume = 37 | issue = 1 | pages = 243–252 | date = January 2021 | pmid = 32361930 | doi = 10.1007/s00381-020-04628-0 | s2cid = 218467172 | doi-access = free }}

In cardiac arrest VNS used in conjunction with cardiopulmonary resuscitation (CPR) has been shown to increase recovery time (return of spontaneous circulation) as well as reduce the number of shocks required when used in conjunction with cardioversion. Numerous pre-clinical studies have shown the effectiveness of VNS in reducing atrial fibrillation and hypertension.

In 2020 during the COVID-19 pandemic, the gammaCore Sapphire CV non-invasive VNS system was granted emergency use authorization for suspected COVID-19 patients experiencing "asthma-related dyspnea and reduced airflow, and for whom approved drug therapies are not tolerated or provide insufficient symptom relief."https://www.fda.gov/media/139968/download Clinical trials show VNS reduces inflammation in COVID patients.{{Cite journal |last1=Tornero |first1=Carlos |last2=Pastor |first2=Ernesto |last3=Garzando |first3=María del Mar |last4=Orduña |first4=Jorge |last5=Forner |first5=Maria J. |last6=Bocigas |first6=Irene |last7=Cedeño |first7=David L. |last8=Vallejo |first8=Ricardo |last9=McClure |first9=Candace K. |last10=Czura |first10=Christopher J. |last11=Liebler |first11=Eric J. |last12=Staats |first12=Peter |date=2022-04-08 |title=Non-invasive Vagus Nerve Stimulation for COVID-19: Results From a Randomized Controlled Trial (SAVIOR I) |journal=Frontiers in Neurology |language=English |volume=13 |doi=10.3389/fneur.2022.820864 |doi-access=free |pmid=35463130 |pmc=9028764 |issn=1664-2295}} In patients with long COVID, VNS is efficacious in reducing inflammatory markers and chronic fatigue.{{Cite journal |last1=Khan |first1=Malik W. Z. |last2=Ahmad |first2=Muhammad |last3=Qudrat |first3=Salma |last4=Afridi |first4=Fatma |last5=Khan |first5=Najia Ali |last6=Afridi |first6=Zain |last7=Fahad |last8=Azeem |first8=Touba |last9=Ikram |first9=Jibran |date=2024-12-01 |title=Vagal nerve stimulation for the management of long COVID symptoms |journal=Infectious Medicine |volume=3 |issue=4 |pages=100149 |doi=10.1016/j.imj.2024.100149 |pmid=39678231 |pmc=11638592 |issn=2772-431X}}

Very small studies have shown possible efficacy of VNS for reduction of Sjogren's fatigue,{{cite journal | vauthors = Tarn J, Evans E, Traianos E, Collins A, Stylianou M, Parikh J, Bai Y, Guan Y, Frith J, Lendrem D, Macrae V, McKinnon I, Simon BS, Blake J, Baker MR, Taylor JP, Watson S, Gallagher P, Blamire A, Newton J, Ng WF | title = The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome | journal = Neuromodulation | volume = 26 | issue = 3 | pages = 681–689 | date = April 2023 | pmid = 37032583 | doi = 10.1016/j.neurom.2022.08.461 | s2cid = 253172246 | doi-access = free }}Inflammation has been associated with both fatigue (see the Wikipedia article on fatigue) and possible VNS mechanism (see below). and for bowel inflammatory disease.{{cite journal | vauthors = Sahn B, Pascuma K, Kohn N, Tracey KJ, Markowitz JF | title = Transcutaneous auricular vagus nerve stimulation attenuates inflammatory bowel disease in children: a proof-of-concept clinical trial | journal = Bioelectronic Medicine | volume = 9 | issue = 1 | pages = 23 | date = October 2023 | pmid = 37849000 | pmc = 10583463 | doi = 10.1186/s42234-023-00124-3 | doi-access = free }}

Piezoelectric BaTiO3 particles conjugated with capsaicin were designed as orally ingested electrostimulators to activate the vagus nerves to combat obesity. This intervention has not yet been tested on the human body.{{cite journal | vauthors = Mac CH, Tai HM, Huang SM, Peng HH, Sharma AK, Nguyen GL, Chang PJ, Wang JT, Chang Y, Lin YJ, Sung HW | title = Orally Ingested Self-Powered Stimulators for Targeted Gut-Brain Axis Electrostimulation to Treat Obesity and Metabolic Disorders | journal = Advanced Materials | volume = 36 | issue = 21 | pages = e2310351 | date = May 2024 | pmid = 38591658 | doi = 10.1002/adma.202310351 | bibcode = 2024AdM....3610351M }}

The causes of VNS efficacy are not well understood.

Mechanisms which may account for the efficacy of VNS include:

There is evidence that VNS results in cortical desynchronization in epilepsy patients who had a favorable clinical response relative to those who did not.{{cite journal | vauthors = Fraschini M, Puligheddu M, Demuru M, Polizzi L, Maleci A, Tamburini G, Congia S, Bortolato M, Marrosu F | title = VNS induced desynchronization in gamma bands correlates with positive clinical outcome in temporal lobe pharmacoresistant epilepsy | journal = Neuroscience Letters | volume = 536 | pages = 14–18 | date = March 2013 | pmid = 23333601 | doi = 10.1016/j.neulet.2012.12.044 | s2cid = 25790383 }}{{cite journal | vauthors = Sangare A, Marchi A, Pruvost-Robieux E, Soufflet C, Crepon B, Ramdani C, Chassoux F, Turak B, Landre E, Gavaret M | title = The Effectiveness of Vagus Nerve Stimulation in Drug-Resistant Epilepsy Correlates with Vagus Nerve Stimulation-Induced Electroencephalography Desynchronization | journal = Brain Connectivity | volume = 10 | issue = 10 | pages = 566–577 | date = December 2020 | pmid = 33073582 | pmc = 7757623 | doi = 10.1089/brain.2020.0798 }}{{cite journal | vauthors = Joseph NM, Steffan P, Becker D, Wernovsky M, Datta P, Ernst L |title=Effects of VNS stimulation on electrocorticography in patients with dual neuro- stimulation devices |journal=Journal of Neurology, Neurosurgery & Psychiatry |date=June 2022 |volume=93 |issue=6 |pages=A3.3–A4 |doi=10.1136/jnnp-2022-abn.9 |s2cid=249067601 }} This makes sense given that seizures consist of abnormal hypersynchronous activity in the brain.

Multiple lines of evidence suggest that inflammation plays a significant role in epilepsy as well as associated neurobehavioral comorbidities such as depression, autism spectrum disorder and cognitive impairment.{{cite journal | vauthors = Paudel YN, Shaikh MF, Shah S, Kumari Y, Othman I | title = Role of inflammation in epilepsy and neurobehavioral comorbidities: Implication for therapy | journal = European Journal of Pharmacology | volume = 837 | pages = 145–155 | date = October 2018 | pmid = 30125565 | doi = 10.1016/j.ejphar.2018.08.020 | s2cid = 52048111 }} There is evidence that VNS has an anti-inflammatory effect through both peripheral and central mechanisms.{{cite journal | vauthors = Wang Y, Zhan G, Cai Z, Jiao B, Zhao Y, Li S, Luo A | title = Vagus nerve stimulation in brain diseases: Therapeutic applications and biological mechanisms | journal = Neuroscience and Biobehavioral Reviews | volume = 127 | pages = 37–53 | date = August 2021 | pmid = 33894241 | doi = 10.1016/j.neubiorev.2021.04.018 | s2cid = 233328858 }}

VNS can change the activity of several neurotransmitter systems involving serotonin, norepinephrine, acetylcholine, dopamine, and GABA.{{cite journal | vauthors = Manta S, El Mansari M, Debonnel G, Blier P | title = Electrophysiological and neurochemical effects of long-term vagus nerve stimulation on the rat monoaminergic systems | journal = The International Journal of Neuropsychopharmacology | volume = 16 | issue = 2 | pages = 459–470 | date = March 2013 | pmid = 22717062 | doi = 10.1017/s1461145712000387 | doi-access = free }}{{cite journal | vauthors = Furmaga H, Shah A, Frazer A | title = Serotonergic and noradrenergic pathways are required for the anxiolytic-like and antidepressant-like behavioral effects of repeated vagal nerve stimulation in rats | journal = Biological Psychiatry | volume = 70 | issue = 10 | pages = 937–945 | date = November 2011 | pmid = 21907323 | doi = 10.1016/j.biopsych.2011.07.020 | s2cid = 206101850 }} The vagus nerve has projects reaching directly in the nucleus of the solitary tract{{Cite journal |last1=Fornai |first1=Francesco |last2=Ruffoli |first2=Riccardo |last3=Giorgi |first3=Filippo S. |last4=Paparelli |first4=Antonio |date=June 2011 |title=The role of locus coeruleus in the antiepileptic activity induced by vagus nerve stimulation |url=https://pubmed.ncbi.nlm.nih.gov/21535457 |journal=The European Journal of Neuroscience |volume=33 |issue=12 |pages=2169–2178 |doi=10.1111/j.1460-9568.2011.07707.x |issn=1460-9568 |pmid=21535457}} and affects a range of subcortical structures including the locus coeruleus, which serves as the primary source of cortical noradrenaline in the brain.{{Cite journal |last1=Poe |first1=Gina R. |last2=Foote |first2=Stephen |last3=Eschenko |first3=Oxana |last4=Johansen |first4=Joshua P. |last5=Bouret |first5=Sebastien |last6=Aston-Jones |first6=Gary |last7=Harley |first7=Carolyn W. |last8=Manahan-Vaughan |first8=Denise |last9=Weinshenker |first9=David |last10=Valentino |first10=Rita |last11=Berridge |first11=Craig |last12=Chandler |first12=Daniel J. |last13=Waterhouse |first13=Barry |last14=Sara |first14=Susan J. |date=November 2020 |title=Locus coeruleus: a new look at the blue spot |journal=Nature Reviews Neuroscience |language=en |volume=21 |issue=11 |pages=644–659 |doi=10.1038/s41583-020-0360-9 |pmid=32943779 |pmc=8991985 |issn=1471-0048}} Stimulation of the vagus nerve in rats has been shown to consistently elevate cortical noradrenaline levels in both the short and long-term.{{Cite journal |last1=Berger |first1=Alexandre |last2=Vespa |first2=Simone |last3=Dricot |first3=Laurence |last4=Dumoulin |first4=Manon |last5=Iachim |first5=Evelina |last6=Doguet |first6=Pascal |last7=Vandewalle |first7=Gilles |last8=El Tahry |first8=Riëm |date=2021 |title=How Is the Norepinephrine System Involved in the Antiepileptic Effects of Vagus Nerve Stimulation? |journal=Frontiers in Neuroscience |volume=15 |pages=790943 |doi=10.3389/fnins.2021.790943 |doi-access=free |issn=1662-4548 |pmc=8675889 |pmid=34924947}} Chronic stimulation of the vagus nerve has also been noted to increase serotonin release and firing in the dorsal raphe nuclei. Other studies in rats have also demonstrated a VNS-dependent increase in dopamine concentrations within the prefrontal cortex and nucleus accumbens.{{Cite journal |last1=Rodenkirch |first1=Charles |last2=Carmel |first2=Jason B. |last3=Wang |first3=Qi |date=2022-07-05 |title=Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems |journal=Frontiers in Neuroscience |language=English |volume=16 |doi=10.3389/fnins.2022.922424 |doi-access=free |pmid=35864985 |pmc=9294458 |issn=1662-453X}}

VNS influences the vagus nerve, which plays a role in the gut-brain axis.{{cite journal | vauthors = Breit S, Kupferberg A, Rogler G, Hasler G | title = Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders | journal = Frontiers in Psychiatry | volume = 9 | pages = 44 | date = 2018 | pmid = 29593576 | pmc = 5859128 | doi = 10.3389/fpsyt.2018.00044 | doi-access = free }}{{cite journal | vauthors = Tarn J, Evans E, Traianos E, Collins A, Stylianou M, Parikh J, Bai Y, Guan Y, Frith J, Lendrem D, Macrae V, McKinnon I, Simon BS, Blake J, Baker MR, Taylor JP, Watson S, Gallagher P, Blamire A, Newton J, Ng WF | title = The Effects of Noninvasive Vagus Nerve Stimulation on Fatigue in Participants With Primary Sjögren's Syndrome | journal = Neuromodulation | volume = 26 | issue = 3 | pages = 681–689 | date = April 2023 | pmid = 37032583 | doi = 10.1016/j.neurom.2022.08.461 }} Research has shown that VNS has an anti-inflammatory effect in patents with irritable bowel syndrome. VNS has been shown to reduce cytokine production as well as modulate gut permeability in patients prior to severe burn injuries.{{Cite journal |last1=Faraji |first1=Navid |last2=Payami |first2=Bahareh |last3=Ebadpour |first3=Negar |last4=Gorji |first4=Ali |date=2025-02-01 |title=Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders |url=https://www.sciencedirect.com/science/article/pii/S0149763424004597#bib164 |journal=Neuroscience & Biobehavioral Reviews |volume=169 |pages=105990 |doi=10.1016/j.neubiorev.2024.105990 |pmid=39716559 |issn=0149-7634|doi-access=free }} Additionally, VNS has been shown to restore dysbiosis in IBD. {{Cite journal |last1=Faraji |first1=Navid |last2=Payami |first2=Bahareh |last3=Ebadpour |first3=Negar |last4=Gorji |first4=Ali |date=2025-02-01 |title=Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders |url=https://www.sciencedirect.com/science/article/pii/S0149763424004597#bbib23 |journal=Neuroscience & Biobehavioral Reviews |volume=169 |pages=105990 |doi=10.1016/j.neubiorev.2024.105990 |pmid=39716559 |issn=0149-7634|doi-access=free }}

Some believe that indirect stimulation of the thalamus may be a key mechanism in VNS efficacy.

A large 25-year retrospective study of 247 patients found a surgical complication rate of 8.6%.{{cite journal | vauthors = Révész D, Rydenhag B, Ben-Menachem E | title = Complications and safety of vagus nerve stimulation: 25 years of experience at a single center | journal = Journal of Neurosurgery. Pediatrics | volume = 18 | issue = 1 | pages = 97–104 | date = July 2016 | pmid = 27015521 | doi = 10.3171/2016.1.peds15534 | doi-access = free }} The common adverse events included infection in 2.6%, hematoma at the surgical site in 1.9% and vocal cord palsy in 1.4%.

In some rare cases where the VNS is not effective, surgery may be necessary to remove the VNS system. The surgery may remove both the generator and the lead.{{cite journal | vauthors = Révész D, Rydenhag B, Ben-Menachem E | title = Complications and safety of vagus nerve stimulation: 25 years of experience at a single center | journal = Journal of Neurosurgery. Pediatrics | volume = 18 | issue = 1 | pages = 97–104 | date = July 2016 | pmid = 27015521 | doi = 10.1016/j.ijporl.2023.111603 | doi-access = free }}

The most common stimulation related side effect at 1 year following implantation are hoarseness in 28% and paraesthesias in the throat-chin region in 12%.{{cite journal | vauthors = Coughlin MK |title=Long-Term Treatment with Vagus Nerve Stimulation in Patients with Refractory Epilepsy |journal=AORN Journal |date=October 2001 |volume=74 |issue=4 |pages=554 |doi=10.1016/s0001-2092(06)61692-x }} At the third year the rate of stimulation related adverse effects decreased substantially with shortness of breath being the most common and occurring in 3.2%. In general, VNS is well tolerated and side effects diminish over time. Also, side effects can be controlled by changing the stimulation parameters.

One small study found sleep apnea in as many as 28% of adults with epilepsy treated with VNS.{{cite journal | vauthors = Salvadé A, Ryvlin P, Rossetti AO | title = Impact of vagus nerve stimulation on sleep-related breathing disorders in adults with epilepsy | journal = Epilepsy & Behavior | volume = 79 | pages = 126–129 | date = February 2018 | pmid = 29287215 | doi = 10.1016/j.yebeh.2017.10.040 | s2cid = 46769980 | url = https://serval.unil.ch/notice/serval:BIB_A91CA09B347D }}

Another small study found significant daytime drowsiness, which could be relieved by reducing the stimulation intensity.{{Cite journal |last1=Aihua |first1=Liu |last2=Lu |first2=Song |last3=Liping |first3=Li |last4=Xiuru |first4=Wang |last5=Hua |first5=Lin |last6=Yuping |first6=Wang |date=October 2014 |title=A controlled trial of transcutaneous vagus nerve stimulation for the treatment of pharmacoresistant epilepsy |url=https://pubmed.ncbi.nlm.nih.gov/25240121 |journal=Epilepsy & Behavior: E&B |volume=39 |pages=105–110 |doi=10.1016/j.yebeh.2014.08.005 |issn=1525-5069 |pmid=25240121}}

Because vagal tone can reduce heart rate, VNS carries the risk of bradycardia (excessively slow heart rate, and even of stopping the heart.

A range of side effects are possible but rare.

The device consists of a generator the size of a matchbox that is implanted under the skin below the person's collarbone. Lead wires from the generator are tunnelled up to the patient's neck and wrapped around the left vagus nerve at the carotid sheath, where it delivers electrical impulses to the nerve.{{cite journal | vauthors = Edwards CA, Kouzani A, Lee KH, Ross EK | title = Neurostimulation Devices for the Treatment of Neurologic Disorders | journal = Mayo Clinic Proceedings | volume = 92 | issue = 9 | pages = 1427–1444 | date = September 2017 | pmid = 28870357 | doi = 10.1016/j.mayocp.2017.05.005 | doi-access = free }}

Implantation of the VNS device is usually done as an out-patient procedure. The procedure goes as follows: an incision is made in the upper left chest and the generator is implanted into a little "pouch" on the left chest under the collarbone. A second incision is made in the neck, so that the surgeon can access the vagus nerve. The surgeon then wraps the leads around the left branch of the vagus nerve, and connects the electrodes to the generator. Once successfully implanted, the generator sends electric impulses to the vagus nerve at regular intervals. The left vagus nerve is stimulated rather than the right because the right plays a role in cardiac function such that stimulating it could have negative cardiac effects.{{cite journal | vauthors = Giordano F, Zicca A, Barba C, Guerrini R, Genitori L | title = Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity | journal = Epilepsia | volume = 58 Suppl 1 | issue = Suppl 1 | pages = 85–90 | date = April 2017 | pmid = 28386925 | doi = 10.1111/epi.13678 | doi-access = free }} The "dose" administered by the device then needs to be set, which is done via a magnetic wand; the parameters adjusted include current, frequency, pulse width, and duty cycle.

The intravenous VNS system produced by LivaNova has stated default settings for use in depression of output power 1.25mA, frequency 20 Hz and pulse width 250 μs, with operation occurring for 30 seconds every 5 minutes (giving a work cycle of 10%). The non-invasive gammaCore device delivers 5000 Hz pulses at a frequency of 25Hz at an intensity of up to 60mA or 30V. Stimulations may be administered for up to two minutes in one sitting, and a maximum of 30 stimulations can be delivered over a 24h period. https://www.gammacore.com/wp-content/uploads/2022/10/gammaCore-Sapphire-SLC-IFU.pdf

External devices work by transcutaneous stimulation and do not require surgery. Electrical impulses are targeted at the cervical branch of the vagus nerve in the neck, or aurical (ear), at points where branches of the vagus nerve have cutaneous representation. Auricular VNS should be located at the concha or inner tragus.{{cite journal | vauthors = Butt MF, Albusoda A, Farmer AD, Aziz Q | title = The anatomical basis for transcutaneous auricular vagus nerve stimulation | journal = Journal of Anatomy | volume = 236 | issue = 4 | pages = 588–611 | date = April 2020 | pmid = 31742681 | pmc = 7083568 | doi = 10.1111/joa.13122 }}

The GammaCore transcutaneous cervical VNS system is recommended by The National Institute for Health and Care Excellence (NICE) for cluster headaches.{{Cite web | url=https://www.nice.org.uk/guidance/mtg46/documents/final-scope | title=Medical technology guidance SCOPE - gammaCore for cluster headache | website=www.nice.org.uk}}

James L. Corning (1855-1923) was an American neurologist who developed the first device for stimulating the vagus nerve towards the end of the 19th century.{{cite journal | vauthors = Lanska DJ | title = J.L. Corning and vagal nerve stimulation for seizures in the 1880s | journal = Neurology | volume = 58 | issue = 3 | pages = 452–459 | date = February 2002 | pmid = 11839848 | doi = 10.1212/wnl.58.3.452 }}

At this time a widely held theory was that excessive blood flow caused seizures.

In the 1880s Corning designed a pronged instrument called the “carotid fork” to compress the carotid artery for the acute treatment of seizures. In addition, he developed the “carotid truss” for prolonged compression of the carotid arteries as a long-term preventative treatment for epilepsy. Then he developed the “electrocompressor” which allowed for the compression of the bilateral carotid arteries as well as electrical stimulation of both the vagus and cervical sympathetic nerves. The idea was to reduce cardiac output and to stimulate cervical sympathetic nerves to constrict cerebral blood vessels. Corning reported dramatic benefits however it was not accepted by his colleagues and ultimately was forgotten.

In the 1930s Biley and Bremer demonstrated the direct influence of VNS on the central nervous system.{{cite journal | vauthors = Bailey P, Bremer F |title=A Sensory Cortical Representation of the Vagus Nerve: With a Note on the Effects of Low Blood Pressure on the Cortical Electrogram |journal=Journal of Neurophysiology |date=September 1938 |volume=1 |issue=5 |pages=405–412 |doi=10.1152/jn.1938.1.5.405 }} In the 1940s and 1950s vagal nerve stimulation was shown to affect EEG activity.{{cite journal | vauthors = George MS, Sackeim HA, Rush AJ, Marangell LB, Nahas Z, Husain MM, Lisanby S, Burt T, Goldman J, Ballenger JC | title = Vagus nerve stimulation: a new tool for brain research and therapy | journal = Biological Psychiatry | volume = 47 | issue = 4 | pages = 287–295 | date = February 2000 | pmid = 10686263 | doi = 10.1016/s0006-3223(99)00308-x | s2cid = 14489190 }}

In 1985 neuroscientist Jacob Zabara{{cite news | vauthors = Squires S |title=Washingtonpost.com: Nation |url=https://www.washingtonpost.com/wp-srv/national/health/daily/march98/epilepsy.htm |newspaper=The Washington Post |date=24 March 1998 |page=Z07 }} proposed that VNS could be used to treat epilepsy.{{cite journal | vauthors = Zabara J |title=Peripheral control of hypersynchronous discharge in epilepsy |journal=Electroencephalography and Clinical Neurophysiology |date=September 1985 |volume=61 |issue=3 |pages=S162 |doi=10.1016/0013-4694(85)90626-1 }} He then demonstrated its efficacy in animal experiments.{{cite journal | vauthors = Zabara J | title = Inhibition of experimental seizures in canines by repetitive vagal stimulation | journal = Epilepsia | volume = 33 | issue = 6 | pages = 1005–1012 | date = November 1992 | pmid = 1464256 | doi = 10.1111/j.1528-1157.1992.tb01751.x | s2cid = 19290172 }} The first human was implanted with a VNS for the treatment of epilepsy in 1988.{{cite journal | vauthors = Penry JK, Dean JC | title = Prevention of intractable partial seizures by intermittent vagal stimulation in humans: preliminary results | journal = Epilepsia | volume = 31 Suppl 2 | issue = s2 | pages = S40–S43 | date = June 1990 | pmid = 2121469 | doi = 10.1111/j.1528-1157.1990.tb05848.x | s2cid = 32134763 }}

In 1997, the US Food and Drug Administration's neurological devices panel met to consider approval of an implanted vagus nerve stimulator (VNS) for epilepsy, requested by Cyberonics (which was subsequently acquired by LivaNova).

The FDA approved an implanted VNS for TR-MDD in 2005.

In April 2017, the FDA cleared marketing of a handheld noninvasive vagus nerve stimulator, called "gammaCore" and made by ElectroCore LLC, for episodic cluster headaches, under the de novo pathway.{{cite news | vauthors = Brauser D |title=FDA Approves Vagus Nerve Stimulation Device for Cluster Headache |url=https://www.medscape.com/viewarticle/878763 |work=Medscape |date=April 18, 2017}}{{cite news |title=GammaCore Device Classification under Section 513(f)(2)(de novo) |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/denovo.cfm?ID=DEN150048 |access-date=6 June 2018 |work=FDA}} In January 2018, the FDA cleared a new use of that device, for the treatment of migraine pain in adults under a 510(k) based on the de novo clearance.{{cite news | vauthors = Brauser D |title=FDA Clears Vagus Nerve Stimulator for Migraine Pain |url= https://www.medscape.com/viewarticle/891930 |work=Medscape |date=January 29, 2018}}{{cite web |title=GammaCore 510(k) Premarket Notification |url=https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMN/pmn.cfm?ID=K173442 |publisher=FDA |access-date=6 June 2018}}

In 2020, electroCore's non-invasive VNS was granted an Emergency Use Authorization for treating COVID-19 patients, given research indicating VNS causes an opening of end terminals in the airways and an anti-inflammatory effect. {{cite news | vauthors = Moore SK |title=Handheld Vagus Nerve Stimulator Gets Emergency Approval for COVID-19 Use |url=https://spectrum.ieee.org/handheld-vagus-nerve-stimulator-gets-emergency-approval-for-covid19-use |work=IEEE Spectrum |date=22 July 2020 }}

In 2021, the same gammaCore nVNS device received Section 510(k) clearance from the FDA to expand its usage for patients with two forms of trigeminal autonomic cephalagia--hemicrania continua and paroxysmal hemicrania.Department of Health and Human Services. Food and Drug Administration (2021). Available at: https://www.accessdata.fda.gov/cdrh_docs/pdf21/K211856.pdf (accessed date on 9th April, 2025).

Because the vagus nerve is associated with many different functions and brain regions, clinical research has been done to determine its usefulness in treating many illnesses. These include various anxiety disorders,{{cite journal | vauthors = Groves DA, Brown VJ | title = Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects | journal = Neuroscience and Biobehavioral Reviews | volume = 29 | issue = 3 | pages = 493–500 | date = May 2005 | pmid = 15820552 | doi = 10.1016/j.neubiorev.2005.01.004 | s2cid = 3021573 }} obesity,{{cite journal | vauthors = de Lartigue G | title = Role of the vagus nerve in the development and treatment of diet-induced obesity | journal = The Journal of Physiology | volume = 594 | issue = 20 | pages = 5791–5815 | date = October 2016 | pmid = 26959077 | pmc = 5063945 | doi = 10.1113/JP271538 }}{{cite journal | vauthors = Göbel CH, Tronnier VM, Münte TF | title = Brain stimulation in obesity | journal = International Journal of Obesity | volume = 41 | issue = 12 | pages = 1721–1727 | date = December 2017 | pmid = 28663570 | doi = 10.1038/ijo.2017.150 | s2cid = 20426017 }} alcohol addiction,{{cite journal | vauthors = Herremans SC, Baeken C | title = The current perspective of neuromodulation techniques in the treatment of alcohol addiction: a systematic review | journal = Psychiatria Danubina | volume = 24 Suppl 1 | issue = suppl 1 | pages = S14–S20 | date = September 2012 | pmid = 22945180 | url = https://hrcak.srce.hr/264977 }} chronic heart failure,{{cite journal | vauthors = Abraham WT, Smith SA | title = Devices in the management of advanced, chronic heart failure | journal = Nature Reviews. Cardiology | volume = 10 | issue = 2 | pages = 98–110 | date = February 2013 | pmid = 23229137 | pmc = 3753073 | doi = 10.1038/nrcardio.2012.178 }} prevention of arrhythmias that can cause sudden cardiac death,{{cite journal | vauthors = Sabbah HN | title = Electrical vagus nerve stimulation for the treatment of chronic heart failure | journal = Cleveland Clinic Journal of Medicine | volume = 78 Suppl 1 | issue = 1 | pages = S24–S29 | date = August 2011 | pmid = 21972326 | pmc = 3817894 | doi = 10.3949/ccjm.78.s1.04 }} autoimmune disorders,{{Citation | vauthors = Fox D | title = Can Zapping the Vagus Nerve Jump-Start Immunity?: An experimental procedure is exposing links between nervous and immune systems | url = https://www.scientificamerican.com/article/can-zapping-the-vagus-nerve-jump-start-immunity/ | publisher = Scientific American | date = 4 May 2017 }}{{cite journal | vauthors = Koopman FA, van Maanen MA, Vervoordeldonk MJ, Tak PP | title = Balancing the autonomic nervous system to reduce inflammation in rheumatoid arthritis | journal = Journal of Internal Medicine | volume = 282 | issue = 1 | pages = 64–75 | date = July 2017 | pmid = 28547815 | doi = 10.1111/joim.12626 | doi-access = free | author4-link = Paul-Peter Tak }} irritable bowel syndrome,{{cite journal | vauthors = Bonaz B, Sinniger V, Pellissier S | title = Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases | journal = Frontiers in Neuroscience | volume = 15 | pages = 650971 | date = 2021 | pmid = 33828455 | pmc = 8019822 | doi = 10.3389/fnins.2021.650971 | doi-access = free }}{{cite journal | vauthors = Payne SC, Furness JB, Burns O, Sedo A, Hyakumura T, Shepherd RK, Fallon JB | title = Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation | journal = Frontiers in Neuroscience | volume = 13 | pages = 418 | date = 2019 | pmid = 31133776 | pmc = 6517481 | doi = 10.3389/fnins.2019.00418 | doi-access = free }}{{cite news | vauthors = Hamza Z |title=Non-Invasive Nerve Stimulation Shows Promise for Younger IBD Patients |url=https://www.medpagetoday.com/meetingcoverage/aibd/96225 |work=Medpage Today |date=15 December 2021 }} Alzheimer's disease,{{cite journal | vauthors = Merrill CA, Jonsson MA, Minthon L, Ejnell H, C-son Silander H, Blennow K, Karlsson M, Nordlund A, Rolstad S, Warkentin S, Ben-Menachem E, Sjögren MJ | title = Vagus nerve stimulation in patients with Alzheimer's disease: Additional follow-up results of a pilot study through 1 year | journal = The Journal of Clinical Psychiatry | volume = 67 | issue = 8 | pages = 1171–1178 | date = August 2006 | pmid = 16965193 | doi = 10.4088/jcp.v67n0801 }}{{cite journal | vauthors = Broncel A, Bocian R, Kłos-Wojtczak P, Kulbat-Warycha K, Konopacki J | title = Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders | journal = Brain Research Bulletin | volume = 155 | pages = 37–47 | date = February 2020 | pmid = 31790720 | doi = 10.1016/j.brainresbull.2019.11.011 | s2cid = 208344249 }} Parkinson's disease,{{cite news | vauthors = Meglio M |title=Noninvasive Vagus Nerve Stimulation for Parkinson Disease Shows Safety, Efficacy |url=https://www.neurologylive.com/view/noninvasive-vagus-nerve-stimulation-parkinson-shows-safety-efficacy |work=Neurology live |date=3 June 2021 }} hypertension,{{cite journal | vauthors = Gierthmuehlen M, Plachta DT | title = Effect of selective vagal nerve stimulation on blood pressure, heart rate and respiratory rate in rats under metoprolol medication | journal = Hypertension Research | volume = 39 | issue = 2 | pages = 79–87 | date = February 2016 | pmid = 26581776 | doi = 10.1038/hr.2015.122 | s2cid = 21184892 | doi-access = free }}{{cite journal | vauthors = Annoni EM, Van Helden D, Guo Y, Levac B, Libbus I, KenKnight BH, Osborn JW, Tolkacheva EG | title = Chronic Low-Level Vagus Nerve Stimulation Improves Long-Term Survival in Salt-Sensitive Hypertensive Rats | journal = Frontiers in Physiology | volume = 10 | pages = 25 | date = 31 January 2019 | pmid = 30766489 | pmc = 6365472 | doi = 10.3389/fphys.2019.00025 | doi-access = free }} several chronic pain conditions,{{cite journal | vauthors = Chakravarthy K, Chaudhry H, Williams K, Christo PJ | title = Review of the Uses of Vagal Nerve Stimulation in Chronic Pain Management | journal = Current Pain and Headache Reports | volume = 19 | issue = 12 | pages = 54 | date = December 2015 | pmid = 26493698 | doi = 10.1007/s11916-015-0528-6 | s2cid = 8117776 }} inflammatory disorders, fibromyalgia and migraines.{{cite journal | vauthors = Johnson RL, Wilson CG | title = A review of vagus nerve stimulation as a therapeutic intervention | journal = Journal of Inflammation Research | volume = 11 | pages = 203–213 | date = 2018 | pmid = 29844694 | pmc = 5961632 | doi = 10.2147/JIR.S163248 | doi-access = free }}{{cite journal | vauthors = Puledda F, Goadsby PJ | title = An Update on Non-Pharmacological Neuromodulation for the Acute and Preventive Treatment of Migraine | journal = Headache | volume = 57 | issue = 4 | pages = 685–691 | date = April 2017 | pmid = 28295242 | doi = 10.1111/head.13069 | s2cid = 205161411 }}

A 2022 study showed that chronic VNS showed strong antidepressant and anxiolytic effects, and improved memory performance in an Alzheimer's Disease animal model.{{cite journal | vauthors = Yesiltepe M, Cimen B, Sara Y | title = Effects of chronic vagal nerve stimulation in the treatment of β-amyloid-induced neuropsychiatric symptoms | journal = European Journal of Pharmacology | volume = 931 | pages = 175179 | date = September 2022 | pmid = 35973478 | doi = 10.1016/j.ejphar.2022.175179 | s2cid = 251558829 }}

{{columns-list|colwidth=30em|

• Cranial electrotherapy stimulation
• Deep brain stimulation
• Electrical brain stimulation
• Electrotherapy
• Low field magnetic stimulation
• Transcranial magnetic stimulation

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• {{cite news | vauthors = Ault A |title=Report casts doubt on VNS approval |url=https://www.thefreelibrary.com/Report+casts+doubt+on+VNS+approval.-a0149222466 |work=Clinical Psychiatry News |date=1 March 2006 }}
• {{cite news | vauthors = Feder BJ |date=September 10, 2006 |title=Battle Lines in Treating Depression |url=https://www.nytimes.com/2006/09/10/business/yourmoney/10cyber.html |work=The New York Times}}

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{{Psychiatry}}

{{Medicine}}

{{DEFAULTSORT:Vagus Nerve Stimulation}}

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