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Beyond the Treatment of Epilepsy: New Applications of Vagus Nerve Stimulation in Psychiatry

  • Markus Kosel and Thomas E. Schlaepfer
Abstract

Vagus nerve stimulation (VNS) in humans generally refers to stimulation of the left vagus nerve at the cervical level. VNS is an established treatment largely devoid of severe side effects for medically refractory partial-onset seizures and has been used in more than 16,000 patients. Over the past 5 years, applications in other neuropsychiatric disorders have been investigated, with a special emphasis on depression. Recent data from an open-label, multi-center pilot study involving 60 patients suggest a potential clinical usefulness in the acute and maintenance treatment of drug-resistant depressive disorder. The perspective of VNS as a long-term treatment with the advantage of assured compliance makes it an interesting technique to potentially treat drug-resistant depression. However, definite therapeutic effects of clinical significance remain to be confirmed in large placebo-controlled trials. Results of clinical pilot studies involving patients suffering from obesity and Alzheimer's disease indicate that VNS might induce weight loss and improve cognition. Besides its clinical usefulness, VNS can be used as a research tool, allowing neuro-physiologic investigations of the parasympathetic system and its interactions with other parts of the central nervous system.

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Corresponding author
Please direct all correspondence to: Thomas E. Schlaepfer, MD, Department of Psychiatry, University Hospital, 3010 Bern, Switzerland; E-mail: schlaepf@jhmi.edu.
References
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1.Penry, JK, Dean, JC. Prevention of intractable partial seizures by intermittent vagal stimulation in humans: Preliminary results. Epilepsia. 1990;31(suppl 2):S40S43.
2.Terry, R, Tarver, WB, Zabara, J. An implantable neurocybernetic prosthesis system. Epilepsia. 1990;31(suppl 2):S33S37.
3.Schachter, SC. Vagus nerve stimulation therapy summary—five years after FDA approval. Neurology. 2002;59(suppl 4):S15S20.
4.Privitera, MD, Welty, TE, Ficker, DM, et al.Vagus nerve stimulation for partial seizures. In: The Cochrane Library. Issue 3, 2002; Oxford.
5.The Vagus Nerve Stimulation Study Group. A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. Neurology. 1995;45:224230.
6.Handforth, A, DeGiorgio, CM, Schachter, SC, et al.Vagus nerve stimulation for partial-onset seizures: a randomized active-control trial. Neurology. 1998;51:4855.
7.DeGiorgio, CM, Schachter, SC, Handforth, A, et al.Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures. Epilepsia. 2000;41:11952000.
8.Binks, AP, Paydarfar, D, Schachter, SC, et al.High strength stimulation of the vagus nerve in awake humans: a lack of cardiorespiratory effects. Respir Physiol. 2001;127:125133.
9.Schachter, SC. Vagus nerve stimulation: where are we? Curr Opin Neurol. 2002;15:201206.
10.Rush, AJ, George, MS, Sackeim, HA, et al.Vagus nerve stimulation for treatment-resistant depression: a multicenter study. Biol Psychiatry. 2000;47:276286.
11.Marangell, LB, Rush, AJ, George, MS, et al.Vagus nerve stimulation for major depressive episodes: one year outcomes. Biol Psychiatry. 2002;51:280287.
12.Physician's Manual: NeuroCybernetic Prothesis System NCP Pulse Generator Models 100 and 101. Houston, Tex: Cyberonics; 2001.
13.Henry, TR. Therapeutic mechanisms of vagus nerve stimulation. Neurology. 2002;59(suppl 4):S3S14.
14.Vonck, K, Van Laere, K, Dedeurwaerdere, S, et al.The mechanism of action of vagus nerve stimulation for refractory epilesy: the current status. J Clin Neurophysiol. 2001;18:394401.
15.George, MS, Sackeim, HA, Rush, AJ, et al.Vagus nerve stimulation: a new tool for brain research and therapy? Biol Psychiatry. 2000;47:287295.
16.Sitdikov, FG, Gil'mutdinova, RI, Minnakhmetov, RR, et al.Asymmetrical effects of vagus nerves on functional parameters of rat heart in postnatal ontogeny. Bull Exp Biol Med. 2000;130:620623.
17.Porges, SW. Orienting in a defensive world: mammalian modifications of our evolutionary heritage—a polyvagal theory. Psychophysiology. 1995;32:301318.
18.Krahl, SE, Senanyake, SS, Handforth, A. Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression on rats. Epilepsia. 2001;42:586589.
19.Zagon, A, Kemeny, AA. Slow hyperpolarization in cortical neurons: a possible mechanism behind vagus nerve stimulation therapy for refractory epilepsy. Epilepsia. 2000;41:13821389.
20.Koo, B. EEG changes with vagus nerve stimulation. J Clin Neurophysiol. 2001;18:434441.
21.Lomarev, MP, Denslow, S, Nahas, Z, et al.Vagus nerve stimulation synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects. J Psychiatr Res. 2002;36:219227.
22.Henry, TR, Votaw, JR, Pennell, PB, et al.Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology. 1999;52:11661173.
23.Narayanan, JT, Watts, R, Haddad, N, et al.Cerebral activation during vagus nerve stimulation: A functional MR study. Epilepsia. 2002;43:15091514.
24.Van Laere, K, Vonck, K, Boon, P, et al.Perfusion SPECT changes after acute and chronic vagus nerve stimulation in relation to prestimulus condition and longterm clinical efficacy. J Nucl Med. 2002;43:733744.
25.Murray, CJ, Lopez, AD. Alternative projections of mortality and disability by cause 1990-2020: Global Burden of Disease Study. Lancet. 1997;349:14981504.
26.Dunner, DL. Acute and maintenance treatment of chronic depression. J Clin Psychiatry. 2001;62(suppl 6):S10S16.
27.Kellner, CH, Fink, M. The efficacy of ECT and ”treatment resistance.” J ECT. 2002;18:12.
28.Sackeim, HA, Prudic, J, Devanand, DP, et al.A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Arch Gen Psychiatry. 2000;57:425434.
29.Sackeim, HA, Haskett, RF, Mulsant, BH, et al.Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA. 2001;285:12991307.
30.McCall, WV. Electroconvulsive therapy in the era of modern psychopharmacology. Int J Neuropsychopharmacol. 2001;4:315324.
31.Ben-Menachem, E. Vagus nerve stimulation, side effects, and long-term safety. J Clin Neurophysiol. 2001;18:415418.
32.Harden, CL. The comorbidity of depression and epilepsy. Neurology. 2002;59(suppl 4):S48S55.
33.Harden, CL, Pulver, MC, Ravdin, LD, et al.A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav. 2000;1:9399.
34.Hoppe, C, Helmstaedter, C, Scherrmann, J, et al.Self-reported mood changes following 6 months of vagus nerve stimulation in epilepsy patients. Epilepsy Behav. 2001;2:225342.
35.Rush, AJ, Linden, M, Zobel, A. Vagusstimulation. Eine neue Behaldlungsoption fur chronifizierte depressive Erkrankungen. Fortschr Neurol Psychiatr. 2002;70:297302.
36.Sackeim, HA, Rush, AJ, George, MS, et al.Vagus nerve stimulation for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology. 2001;25:713728.
37.George, MS, Nahas, Z, Bohning, D, et al.Vagus nerve stimulation therapy: a research update. Neurology. 2002;59(suppl 4):S56S61.
38.Roslin, M, Kurian, M. Vagus nerve stimulation in the treatment of morbid obesity. In: Schachter, SC, Schmidt, D, eds. Vagus Nerve Stimulation. London, England: Martin Dunitz; 2002:113121.
39.Sjogren, MJ, Hellstrom, PT, Jonsson, MA, et al.Cognition-enhancing effect of vagus nerve stimulation in patients with Alzheimer's disease: a pilot study. J Clin Psychiatry. 2002;63:972980.
40.Annegers, JF, Coan, SP, Hauser, WA, et al.Epilepsy, vagal nerve stimulation by the NCP system, mortality, and sudden, unexpected, unexplained death. Epilepsia. 1998;39:206212.
41.Annegers, JF, Coan, SP, Hauser, WA, et al.Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death. Epilepsia. 2000;41:549–453.
42.Tatum, WO, Moore, DB, Stecker, MM, et al.Ventricular asystole during vagus nerve stimulation for humans. Neurology. 1999;52:12671269.
43.Agnew, WF, McCreery, DB. Considerations for safety with chronically implanted nerve electrodes. Epilepsia. 1900;31(suppl 2):S27S32.
44.Tubbs, RS, Patwardhan, R, Palmer, CA, et al.Histological appearance of a chronically stimulated vagus nerve in a pediatric patient. Pediatr Neurosurg. 2001;35:99102.
45.Charous, SJ, Kempster, G, Manders, E, et al.The effect of vagal nerve stimulation on voice. Laryngoscope. 2001;111:20282031.
46.DeGiorgio, CM, Thompson, J, Lewis, P, et al.Vaguss nerve stimulation: analysis of device parameters in 154 patients during the long-term XE5 Study. Epilepsia. 2001;42:10171020.
47.Lewis, ME, Al-Khaladi, AH, Bonser, RS, et al.Vagus nerve stimulation decreases left ventricular contractility in vivo in the human and pig heart. J Physiol. 2001;534:547552.
48.Frei, MG, Osorio, I. Left vagus nerve stimulation with the neurocybernetic prosthesis has complex effects on heart rate and on its variability in humans. Epilepsia. 2001;42:10071016.
49.Banzett, RB, Guz, A, Paydarfar, D, et al.Cardiorespiratory variables and sensation during stimulation of the left vagus in patients with epilepsy. Epilepsy Res. 1999;35:111.
50.Sanossian, N, Haut, S. Chronic diarrhea associated with vagal nerve stimulation. Neurology. 2002;58:330.
51.Kim, W, Clancy, RR, Liu, GT. Homer syndrome associated with implantation of a vagus nerve stimulator. Am J Ophthalmol. 2001;131:383384.
52.Leijten, FS, Van Rijen, PC. Stimulation of the phrenic nerve as a complication of vagus nerve pacing in a patient with epilepsy. Neurology. 1998;51:12241225.
53.Iriarte, J, Artieda, J, Alegre, M, et al.Spam of the sternocleidomastoid muscle induced by vagal nerve stimulation. Neurology. 2001;57:23192320.
54.Malow, BA, Edwards, J, Merzec, M, et al.Effects of vagus nerve stimulation on respiration during sleep. Neurology. 2000;55:14501454.
55.Lundgren, J, Ekberg, O, Olsson, R. Aspiration: a potential complication to vagus nerve stimulation. Epilepsia. 1998;39:9981000.
56.Schallert, G, Foster, J, Lindquist, N, et al.Chronic stimulation of the left vagal nerve in children: effect on swallowing. Epilepsia. 1998;39:11131114.
57.Heck, C, Helmers, SL, DeGiorgio, CM. Vagus nerve stimulation therapy, epilepsy and device parameters: scientific basis and recommendations for use. Neurology. 2002;59(suppl 4):S31S37.
58.Sackeim, HA, Keilp, JG, Rush, AJ, et al.The effects of vagus nerve stimulation on cognitive performance in patients with treatment-resistant depression. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14:5362.
59.Clark, KB, Naritoku, DK, Smith, DC, et al.Enhanced recognition memory following vagus nerve stimulation in human subjects. Nat Neurosci. 1999;2:9498.
60.Helmstaedter, C, Hoppe, C, Elger, CE. Memory alterations during acute high-intensity vagus nerve stimulation. Epilepsy Res. 2001;47:3742.
61.Koo, B, Ham, SD, Sood, S, et al.Human vagus nerve electrophysiology: a guide to vagus nerve stimulation parameters. J Clin Neurophysiol. 2001;18:429433.
62.Boon, P, D'Havé, M, Van Walleghem, P, et al.Direct medical costs of refractory epilepsy incurred by three different treatment modalities: a prospective assessment. Epilepsia. 2002;43:96102.
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