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Vagus nerve stimulation in psychiatry: a systematic review of the available evidence

  • Psychiatry and Preclinical Psychiatric Studies - Review Article
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Abstract

Invasive and non-invasive vagus nerve stimulation (VNS) is a promising add-on treatment for treatment-refractory depression, but is also increasingly evaluated for its application in other psychiatric disorders, such as dementia, schizophrenia, somatoform disorder, and others. We performed a systematic review aiming to give a detailed overview of the available evidence of the efficacy of VNS for the treatment of psychiatric disorders. Data derived from animal models, experimental trials without health-related outcomes, case reports, single-session studies, and reviews were excluded. From 1292 publications, 33 records were included for further analyses: 25 focused on VNS as treatment of unipolar or bipolar major depressive disorder and one investigated the neurocognitive improvement after VNS in major depressive disorder. Seven focused on the improvement of cognitive function in Alzheimer´s disease, improvement of schizophrenia symptoms, treatment of obsessive compulsive disorder (OCD), panic disorder (PD) and post-traumatic stress disorder (PTSD), treatment resistant rapid-cycling bipolar disorder, treatment of fibromyalgia, and Prader–Willi syndrome. A total of 29 studies used invasive VNS, while four studies used non-invasive, transcutaneous VNS. Only 7 out of 33 studies investigated conditions other than affective disorders. The efficacy data of VNS in affective disorders is promising, whereas more in controlled and naturalistic studies are needed. In other conditions like schizophrenia, Alzheimer’s disease, OCD, PD, PTSD, and fibromyalgia, either no effects or preliminary data on efficacy were reported. At this point, no final conclusion can be made regarding the efficacy of VNS to improve symptoms in psychiatric disorders other than in affective disorders.

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References

  • 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 (2013) Vagus nerve stimulation therapy randomized to different amounts of electrical charge for treatment-resistant depression: acute and chronic effects. Brain Stimul 6(4):631–640. doi:10.1016/j.brs.2012.09.013

    Article  PubMed  Google Scholar 

  • Albert U, Maina G, Aguglia A, Vitalucci A, Bogetto F, Fronda C, Ducati A, Lanotte M (2015) Vagus nerve stimulation for treatment-resistant mood disorders: a long-term naturalistic study. BMC Psychiatry 15:64. doi:10.1186/s12888-015-0435-8

    Article  PubMed  PubMed Central  Google Scholar 

  • Bajbouj M, Merkl A, Schlaepfer TE, Frick C, Zobel A, Maier W, O’Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Muller-Siecheneder F, Audenaert K, van den Abbeele D, Matthews K, Christmas D, Eljamel S, Heuser I (2010) Two-year outcome of vagus nerve stimulation in treatment-resistant depression. J Clin Psychopharmacol 30(3):273–281. doi:10.1097/JCP.0b013e3181db8831

    Article  PubMed  Google Scholar 

  • Berry SM, Broglio K, Bunker M, Jayewardene A, Olin B, Rush AJ (2013) A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices 6:17–35. doi:10.2147/MDER.S41017

    Google Scholar 

  • Christmas D, Steele JD, Tolomeo S, Eljamel MS, Matthews K (2013) Vagus nerve stimulation for chronic major depressive disorder: 12-month outcomes in highly treatment-refractory patients. J Affect Disord 150(3):1221–1225. doi:10.1016/j.jad.2013.05.080

    Article  PubMed  Google Scholar 

  • Cleare A, Pariante CM, Young AH, Anderson IM, Christmas D, Cowen PJ, Dickens C, Ferrier IN, Geddes J, Gilbody S, Haddad PM, Katona C, Lewis G, Malizia A, McAllister-Williams RH, Ramchandani P, Scott J, Taylor D, Uher R, Members of the Consensus M (2015) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines. J Psychopharmacol 29(5):459–525. doi:10.1177/0269881115581093

    Article  CAS  PubMed  Google Scholar 

  • Corcoran CD, Thomas P, Phillips J, O’Keane V (2006) Vagus nerve stimulation in chronic treatment-resistant depression: preliminary findings of an open-label study. Br J Psychiatry 189:282–283. doi:10.1192/bjp.bp.105.018689

    Article  PubMed  Google Scholar 

  • Cristancho P, Cristancho MA, Baltuch GH, Thase ME, O’Reardon JP (2011) Effectiveness and safety of vagus nerve stimulation for severe treatment-resistant major depression in clinical practice after FDA approval: outcomes at 1 year. J Clin Psychiatry 72(10):1376–1382. doi:10.4088/JCP.09m05888blu

    Article  CAS  PubMed  Google Scholar 

  • Dayan E, Censor N, Buch ER, Sandrini M, Cohen LG (2013) Noninvasive brain stimulation: from physiology to network dynamics and back. Nat Neurosci 16(7):838–844. doi:10.1038/nn.3422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dell’Osso B, Oldani L, Palazzo MC, Balossi I, Ciabatti M, Altamura AC (2013) Vagus nerve stimulation in treatment-resistant depression: acute and follow-up results of an Italian case series. J ECT 29(1):41–44. doi:10.1097/YCT.0b013e3182735ef0

    PubMed  Google Scholar 

  • DGPPN (2015) S3-Leitlinie/Nationale Versorgungsleitlinie Unipolare Depression. https://www.dgppn.de/fileadmin/user_upload/_medien/download/pdf/kurzversion-leitlinien/S3-NVLdepression-lang_2015.pdf www.depression.versorgungsleitlinien.de

  • Dietrich S, Smith J, Scherzinger C, Hofmann-Preiss K, Freitag T, Eisenkolb A, Ringler R (2008) A novel transcutaneous vagus nerve stimulation leads to brainstem and cerebral activations measured by functional MRI. Biomed Tech Biomed Eng 53(3):104–111. doi:10.1515/BMT.2008.022

    Article  Google Scholar 

  • Englot DJ, Chang EF, Auguste KI (2011) Vagus nerve stimulation for epilepsy: a meta-analysis of efficacy and predictors of response. J Neurosurg 115(6):1248–1255. doi:10.3171/2011.7.JNS11977

    Article  PubMed  Google Scholar 

  • George MS, Rush AJ, Marangell LB, Sackeim HA, Brannan SK, Davis SM, Howland R, Kling MA, Moreno F, Rittberg B, Dunner D, Schwartz T, Carpenter L, Burke M, Ninan P, Goodnick P (2005) A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biol Psychiatry 58(5):364–373. doi:10.1016/j.biopsych.2005.07.028

    Article  PubMed  Google Scholar 

  • George MS, Ward HE Jr, Ninan PT, Pollack M, Nahas Z, Anderson B, Kose S, Howland RH, Goodman WK, Ballenger JC (2008) A pilot study of vagus nerve stimulation (VNS) for treatment-resistant anxiety disorders. Brain Stimul 1(2):112–121. doi:10.1016/j.brs.2008.02.001

    Article  CAS  PubMed  Google Scholar 

  • Hasan A, Wolff-Menzler C, Pfeiffer S, Falkai P, Weidinger E, Jobst A, Hoell I, Malchow B, Yeganeh-Doost P, Strube W, Quast S, Muller N, Wobrock T (2015) Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: a bicentric randomized controlled pilot study. Eur Arch Psychiatry Clin Neurosci 265(7):589–600. doi:10.1007/s00406-015-0618-9

    Article  PubMed  Google Scholar 

  • He W, Jing X, Wang X, Rong P, Li L, Shi H, Shang H, Wang Y, Zhang J, Zhu B (2013) Transcutaneous auricular vagus nerve stimulation as a complementary therapy for pediatric epilepsy: a pilot trial. Epilepsy Behav 28(3):343–346. doi:10.1016/j.yebeh.2013.02.001

    Article  PubMed  Google Scholar 

  • Hein E, Nowak M, Kiess O, Biermann T, Bayerlein K, Kornhuber J, Kraus T (2013) Auricular transcutaneous electrical nerve stimulation in depressed patients: a randomized controlled pilot study. J Neural Transm 120(5):821–827. doi:10.1007/s00702-012-0908-6

    Article  PubMed  Google Scholar 

  • Henry TR, Bakay RA, Pennell PB, Epstein CM, Votaw JR (2004) Brain blood-flow alterations induced by therapeutic vagus nerve stimulation in partial epilepsy: II. Prolonged effects at high and low levels of stimulation. Epilepsia 45(9):1064–1070. doi:10.1111/j.0013-9580.2004.03104.x

    Article  PubMed  Google Scholar 

  • Kosel M, Brockmann H, Frick C, Zobel A, Schlaepfer TE (2011) Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex. Psychiatry Res 191(3):153–159. doi:10.1016/j.pscychresns.2010.11.004

    Article  PubMed  Google Scholar 

  • Kraus T, Kiess O, Hosl K, Terekhin P, Kornhuber J, Forster C (2013) CNS BOLD fMRI effects of sham-controlled transcutaneous electrical nerve stimulation in the left outer auditory canal–a pilot study. Brain Stimul 6(5):798–804. doi:10.1016/j.brs.2013.01.011

    Article  PubMed  Google Scholar 

  • Lange G, Janal MN, Maniker A, Fitzgibbons J, Fobler M, Cook D, Natelson BH (2011) Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Pain Med 12(9):1406–1413. doi:10.1111/j.1526-4637.2011.01203.x

    Article  PubMed  PubMed Central  Google Scholar 

  • Lefaucheur JP, Andre-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H, Di Lazzaro V, Filipovic SR, Hummel FC, Jaaskelainen SK, Kimiskidis VK, Koch G, Langguth B, Nyffeler T, Oliviero A, Padberg F, Poulet E, Rossi S, Rossini PM, Rothwell JC, Schonfeldt-Lecuona C, Siebner HR, Slotema CW, Stagg CJ, Valls-Sole J, Ziemann U, Paulus W, Garcia-Larrea L (2014) Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin Neurophysiol 125(11):2150–2206. doi:10.1016/j.clinph.2014.05.021

    Article  PubMed  Google Scholar 

  • Lett TA, Voineskos AN, Kennedy JL, Levine B, Daskalakis ZJ (2014) Treating working memory deficits in schizophrenia: a review of the neurobiology. Biol Psychiatry 75(5):361–370. doi:10.1016/j.biopsych.2013.07.026

    Article  PubMed  Google Scholar 

  • Liu J, Fang J, Wang Z, Rong P, Hong Y, Fan Y, Wang X, Park J, Jin Y, Liu C, Zhu B, Kong J (2016) Transcutaneous vagus nerve stimulation modulates amygdala functional connectivity in patients with depression. J Affect Disord 205:319–326. doi:10.1016/j.jad.2016.08.003

    Article  PubMed  Google Scholar 

  • Manning KE, McAllister CJ, Ring HA, Finer N, Kelly CL, Sylvester KP, Fletcher PC, Morrell NW, Garnett MR, Manford MR, Holland AJ (2016) Novel insights into maladaptive behaviours in Prader–Willi syndrome: serendipitous findings from an open trial of vagus nerve stimulation. J Intellect Disabil Res 60(2):149–155. doi:10.1111/jir.12203

    Article  CAS  PubMed  Google Scholar 

  • Marangell LB, Rush AJ, George MS, Sackeim HA, Johnson CR, Husain MM, Nahas Z, Lisanby SH (2002) Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry 51(4):280–287

    Article  PubMed  Google Scholar 

  • Marangell LB, Suppes T, Zboyan HA, Prashad SJ, Fischer G, Snow D, Sureddi S, Allen JC (2008) A 1-year pilot study of vagus nerve stimulation in treatment-resistant rapid-cycling bipolar disorder. J Clin Psychiatry 69(2):183–189

    Article  PubMed  Google Scholar 

  • Martin JL, Martin-Sanchez E (2012) Systematic review and meta-analysis of vagus nerve stimulation in the treatment of depression: variable results based on study designs. Eur Psychiatry 27(3):147–155. doi:10.1016/j.eurpsy.2011.07.006

    Article  CAS  PubMed  Google Scholar 

  • Merrill CA, Jonsson MA, Minthon L, Ejnell H, CsS H, Blennow K, Karlsson M, Nordlund A, Rolstad S, Warkentin S, Ben-Menachem E, Sjogren MJ (2006) Vagus nerve stimulation in patients with Alzheimer’s disease: additional follow-up results of a pilot study through 1 year. J Clin Psychiatry 67(8):1171–1178

    Article  CAS  PubMed  Google Scholar 

  • Milev RV, Giacobbe P, Kennedy SH, Blumberger DM, Daskalakis ZJ, Downar J, Modirrousta M, Patry S, Vila-Rodriguez F, Lam RW, MacQueen GM, Parikh SV, Ravindran AV, Group CDW (2016) Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 4. Neurostimulation Treatments. Can J Psychiatry 61(9):561–575. doi:10.1177/0706743716660033

    Article  PubMed  Google Scholar 

  • Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Reprint–preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Phys Ther 89(9):873–880

    PubMed  Google Scholar 

  • Muller HH, Kornhuber J, Maler JM, Sperling W (2013) The effects of stimulation parameters on clinical outcomes in patients with vagus nerve stimulation implants with major depression. J ECT 29(3):e40–e42. doi:10.1097/YCT.0b013e318290f7ed

    Article  PubMed  Google Scholar 

  • Nahas Z, Marangell LB, Husain MM, Rush AJ, Sackeim HA, Lisanby SH, Martinez JM, George MS (2005) Two-year outcome of vagus nerve stimulation (VNS) for treatment of major depressive episodes. J Clin Psychiatry 66(9):1097–1104

    Article  PubMed  Google Scholar 

  • Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, George MS, Charney DS, Brannan SK (2006) VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 31(7):1345–1355. doi:10.1038/sj.npp.1301082

    Article  PubMed  Google Scholar 

  • NICE (2012) Vagus nervagus nerve stimulation for treatment-resistante stimulation for treatment-resistant depression. http://nice.org.uk/guidance/ipg330

  • Nierenberg AA, Alpert JE, Gardner-Schuster EE, Seay S, Mischoulon D (2008) Vagus nerve stimulation: 2-year outcomes for bipolar versus unipolar treatment-resistant depression. Biol Psychiatry 64(6):455–460. doi:10.1016/j.biopsych.2008.04.036

    Article  PubMed  Google Scholar 

  • Olin B, Jayewardene AK, Bunker M, Moreno F (2012) Mortality and suicide risk in treatment-resistant depression: an observational study of the long-term impact of intervention. PLoS One 7(10):e48002. doi:10.1371/journal.pone.0048002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ridding MC, Rothwell JC (2007) Is there a future for therapeutic use of transcranial magnetic stimulation? Nat Rev Neurosci 8(7):559–567. doi:10.1038/nrn2169

    Article  CAS  PubMed  Google Scholar 

  • Rong P, Liu J, Wang L, Liu R, Fang J, Zhao J, Zhao Y, Wang H, Vangel M, Sun S, Ben H, Park J, Li S, Meng H, Zhu B, Kong J (2016) Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: a nonrandomized controlled pilot study. J Affect Disord 195:172–179. doi:10.1016/j.jad.2016.02.031

    Article  PubMed  Google Scholar 

  • Rush AJ, George MS, Sackeim HA, Marangell LB, Husain MM, Giller C, Nahas Z, Haines S, Simpson RK Jr, Goodman R (2000) Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry 47(4):276–286

    Article  CAS  PubMed  Google Scholar 

  • 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 (2005a) Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 58(5):347–354. doi:10.1016/j.biopsych.2005.05.025

    Article  PubMed  Google Scholar 

  • Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ (2005b) Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 58(5):355–363. doi:10.1016/j.biopsych.2005.05.024

    Article  PubMed  Google Scholar 

  • Sackeim HA, Keilp JG, Rush AJ, George MS, Marangell LB, Dormer JS, Burt T, Lisanby SH, Husain M, Cullum CM, Oliver N, Zboyan H (2001a) The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression. Neuropsychiatry Neuropsychol Behav Neurol 14(1):53–62

    CAS  PubMed  Google Scholar 

  • Sackeim HA, Rush AJ, George MS, Marangell LB, Husain MM, Nahas Z, Johnson CR, Seidman S, Giller C, Haines S, Simpson RK Jr, Goodman RR (2001b) Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25(5):713–728. doi:10.1016/S0893-133X(01)00271-8

    Article  CAS  PubMed  Google Scholar 

  • Sackeim HA, Brannan SK, Rush AJ, George MS, Marangell LB, Allen J (2007) Durability of antidepressant response to vagus nerve stimulation (VNS). Int J Neuropsychopharmacol 10(6):817–826. doi:10.1017/S1461145706007425

    Article  CAS  PubMed  Google Scholar 

  • Schlaepfer TE, Frick C, Zobel A, Maier W, Heuser I, Bajbouj M, O’Keane V, Corcoran C, Adolfsson R, Trimble M, Rau H, Hoff HJ, Padberg F, Muller-Siecheneder F, Audenaert K, Van den Abbeele D, Stanga Z, Hasdemir M (2008) Vagus nerve stimulation for depression: efficacy and safety in a European study. Psychol Med 38(5):651–661. doi:10.1017/S0033291707001924

    Article  CAS  PubMed  Google Scholar 

  • Sjogren MJ, Hellstrom PT, Jonsson MA, Runnerstam M, Silander HC, Ben-Menachem E (2002) Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer’s disease: a pilot study. J Clin Psychiatry 63(11):972–980

    Article  PubMed  Google Scholar 

  • Sperling W, Reulbach U, Kornhuber J (2009) Clinical benefits and cost effectiveness of vagus nerve stimulation in a long-term treatment of patients with major depression. Pharmacopsychiatry 42(3):85–88. doi:10.1055/s-0028-1103294

    Article  CAS  PubMed  Google Scholar 

  • Stefan H, Kreiselmeyer G, Kerling F, Kurzbuch K, Rauch C, Heers M, Kasper BS, Hammen T, Rzonsa M, Pauli E, Ellrich J, Graf W, Hopfengartner R (2012) Transcutaneous vagus nerve stimulation (t-VNS) in pharmacoresistant epilepsies: a proof of concept trial. Epilepsia 53(7):e115–e118. doi:10.1111/j.1528-1167.2012.03492.x

    Article  PubMed  Google Scholar 

  • Tisi G, Franzini A, Messina G, Savino M, Gambini O (2014) Vagus nerve stimulation therapy in treatment-resistant depression: a series report. Psychiatry Clin Neurosci 68(8):606–611

    Article  PubMed  Google Scholar 

  • Tortella G, Casati R, Aparicio LV, Mantovani A, Senco N, D’Urso G, Brunelin J, Guarienti F, Selingardi PM, Muszkat D, Junior Bde S, Valiengo L, Moffa AH, Simis M, Borrione L, Brunoni AR (2015) Transcranial direct current stimulation in psychiatric disorders. World J Psychiatry 5(1):88–102. doi:10.5498/wjp.v5.i1.88

    PubMed  PubMed Central  Google Scholar 

  • Wani A, Trevino K, Marnell P, Husain MM (2013) Advances in brain stimulation for depression. Ann Clin Psychiatry 25(3):217–224

    PubMed  Google Scholar 

  • Wolff-Menzler C (2016) The effectivity of vagus nerve stimulation (VNS) in treatment-resistent depression and comorbid personality disorder. Meeting of the German Society of Biological Psychiatry (Deutsche Gesellschaft für Biologische Psychiatrie), 2010

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Correspondence to Camelia-Lucia Cimpianu.

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C Cimpianu reports no conflicts of interest. W. Strube has received paid speakership by Mag and More. U. Palm received a paid speakership from NeuroCare Group. P. Falkai was honorary speaker for Janssen-Cilag, Astra-Zeneca, Eli Lilly, Bristol Myers-Squibb, Lundbeck, Pfizer, Bayer Vital, SmithKline Beecham, Wyeth, and Essex. During the last 5 years, but not presently, he was a member of the advisory boards of Janssen-Cilag, AstraZeneca, Eli Lilly, and Lundbeck. A. Hasan received a paid speakership from Desitin, Otsuka and Lundbeck. He was member of an advisory board of Roche and Lundbeck.

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Cimpianu, CL., Strube, W., Falkai, P. et al. Vagus nerve stimulation in psychiatry: a systematic review of the available evidence. J Neural Transm 124, 145–158 (2017). https://doi.org/10.1007/s00702-016-1642-2

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