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Vagus nerve stimulation for depression: efficacy and safety in a European study

Published online by Cambridge University Press:  04 January 2008

T. E. Schlaepfer ,
C. Frick ,
A. Zobel ,
W. Maier ,
I. Heuser ,
M. Bajbouj ,
V. O'Keane ,
C. Corcoran ,
R. Adolfsson  and
M. Trimble
...Show all authors
T. E. Schlaepfer*
Affiliation:
Department of Psychiatry, University Hospital, Bern, Switzerland Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany Departments of Psychiatry and Mental Health, The Johns Hopkins University, Baltimore, MD, USA
C. Frick
Affiliation:
Department of Psychiatry, University Hospital, Bern, Switzerland Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
A. Zobel
Affiliation:
Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
W. Maier
Affiliation:
Department of Psychiatry and Psychotherapy, University Hospital, Bonn, Germany
I. Heuser
Affiliation:
Psychiatrische Klinik der FU Berlin, Berlin, Germany
M. Bajbouj
Affiliation:
Psychiatrische Klinik der FU Berlin, Berlin, Germany
V. O'Keane
Affiliation:
Beaumont Hospital, Department of Psychiatry, Dublin, Ireland
C. Corcoran
Affiliation:
Beaumont Hospital, Department of Psychiatry, Dublin, Ireland
R. Adolfsson
Affiliation:
University Hospital Umea, Umea, Sweden
M. Trimble
Affiliation:
National Hospital for Neurology and Neurosurgery, Department of Neuropsychiatry and Neurology, London, UK
H. Rau
Affiliation:
Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany Alcohol Rehabilitation Clinic, Wilhelmsdorf, Germany
H.-J. Hoff
Affiliation:
Evangelisches Krankenhaus Bielefeld, Bielefeld, Germany
F. Padberg
Affiliation:
Departments of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany
F. Müller-Siecheneder
Affiliation:
Departments of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany
K. Audenaert
Affiliation:
University Hospital Gent, Gent, Belgium
D. Van den Abbeele
Affiliation:
University Hospital Gent, Gent, Belgium
K. Matthews
Affiliation:
Ninewells Hospital and Medical School, Department of Psychiatry, Dundee, UK
D. Christmas
Affiliation:
Ninewells Hospital and Medical School, Department of Psychiatry, Dundee, UK
Z. Stanga
Affiliation:
Department of Psychiatry, University Hospital, Bern, Switzerland
M. Hasdemir
Affiliation:
Lindenhof Hospital, Department of Neurosurgery, Bern, Switzerland
*
*Address for correspondence: T. E. Schlaepfer, M.D., Department of Psychiatry/University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. (Email: [email protected])
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Abstract

Background

Vagus nerve stimulation (VNS) therapy is associated with a decrease in seizure frequency in partial-onset seizure patients. Initial trials suggest that it may be an effective treatment, with few side-effects, for intractable depression.

Method

An open, uncontrolled European multi-centre study (D03) of VNS therapy was conducted, in addition to stable pharmacotherapy, in 74 patients with treatment-resistant depression (TRD). Treatment remained unchanged for the first 3 months; in the subsequent 9 months, medications and VNS dosing parameters were altered as indicated clinically.

Results

The baseline 28-item Hamilton Depression Rating Scale (HAMD-28) score averaged 34. After 3 months of VNS, response rates (⩾50% reduction in baseline scores) reached 37% and remission rates (HAMD-28 score <10) 17%. Response rates increased to 53% after 1 year of VNS, and remission rates reached 33%. Response was defined as sustained if no relapse occurred during the first year of VNS after response onset; 44% of patients met these criteria. Median time to response was 9 months. Most frequent side-effects were voice alteration (63% at 3 months of stimulation) and coughing (23%).

Conclusions

VNS therapy was effective in reducing severity of depression; efficacy increased over time. Efficacy ratings were in the same range as those previously reported from a USA study using a similar protocol; at 12 months, reduction of symptom severity was significantly higher in the European sample. This might be explained by a small but significant difference in the baseline HAMD-28 score and the lower number of treatments in the current episode in the European study.

Keywords

Brain stimulationmajor depressiontreatment resistancevagus nerve
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 5 , May 2008 , pp. 651 - 661
Copyright
Copyright © Cambridge University Press 2008

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References

Andrews, JM, Nemeroff, CB (1994). Contemporary management of depression. American Journal of Medicine 97, 24S–32S.CrossRefGoogle ScholarPubMed
Ben-Menachem, E (2001). Vagus nerve stimulation, side effects, and long-term safety. Journal of Clinical Neurophysiology 18, 415–418.CrossRefGoogle ScholarPubMed
Ben-Menachem, E, Manon-Espaillat, R, Ristanovic, R, Wilder, BJ, Stefan, H, Mirza, W, Tarver, WB, Wernicke, JF (1994). Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. First International Vagus Nerve Stimulation Study Group. Epilepsia 35, 616–626.CrossRefGoogle ScholarPubMed
Carpenter, LL, Moreno, FA, Kling, MA, Anderson, GM, Regenold, WT, Labiner, DM, Price, LH (2004). Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients. Biological Psychiatry 56, 418–426.CrossRefGoogle ScholarPubMed
Chae, JH, Nahas, Z, Lomarev, M, Denslow, S, Lorberbaum, JP, Bohning, DE, George, MS (2003). A review of functional neuroimaging studies of vagus nerve stimulation (VNS). Journal of Psychiatric Research 37, 443–455.CrossRefGoogle ScholarPubMed
Conway, CR, Sheline, YI, Chibnall, JT, George, MS, Fletcher, JW, Mintun, MA (2006). Cerebral blood flow changes during vagus nerve stimulation for depression. Psychiatry Research 146, 179–184.CrossRefGoogle ScholarPubMed
Dago, P, Quitkin, F (1995). Role of the placebo response in the treatment of depressive disorders. CNS Drugs 4, 335–340.CrossRefGoogle Scholar
Dorr, AE, Debonnel, G (2006). Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. Journal of Pharmacology and Experimental Therapeutics 318, 890–898.CrossRefGoogle ScholarPubMed
Dunner, D, Rush, A, Russell, J, Burke, M, Woodard, S, Wingard, P, Allen, J (2006). Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. Journal of Clinical Psychiatry 67, 688–695.CrossRefGoogle ScholarPubMed
Elger, G, Hoppe, C, Falkai, P, Rush, A, Elger, C (2000). Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Research 42, 203–210.CrossRefGoogle ScholarPubMed
FDA (1995). COSTART: Coding Symbols for Thesaurus of Adverse Reaction Terms. US Department of Health and Human Services, Center for Drug Evaluation and Research, Food and Drug Administration, Center for Drugs and Biologics: Rockville, MD.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. Biological Psychiatry 58, 364–373.CrossRefGoogle ScholarPubMed
George, MS, Sackeim, HA, Rush, AJ, Marangell, LB, Nahas, Z, Husain, MM, Lisanby, S, Burt, T, Goldman, J, Ballenger, JC (2000). Vagus nerve stimulation: a new tool for brain research and therapy. Biological Psychiatry 47, 287–295.CrossRefGoogle ScholarPubMed
Groves, DA, Brown, VJ (2005). Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neuroscience and Biobehavioral Reviews 29, 493–500.CrossRefGoogle ScholarPubMed
Hamilton, M (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278–296.CrossRefGoogle ScholarPubMed
Handforth, A, DeGiorgio, C, Schachter, S, Uthman, B, Naritoku, D, Tecoma, E (1998). Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51, 48–55.CrossRefGoogle ScholarPubMed
Harden, CL, Pulver, MC, Ravdin, LD, Nikolov, B, Halper, JP, Labar, DR (2000). A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy and Behavior 1, 93–99.CrossRefGoogle ScholarPubMed
Helmstaedter, C, Hoppe, C, Elger, CE (2001). Memory alterations during acute high-intensity vagus nerve stimulation. Epilepsy Research 47, 37–42.CrossRefGoogle ScholarPubMed
Henry, TR, Votaw, JR, Pennell, PB, Epstein, CM, Bakay, RAE, Faber, TL, Grafton, ST, Hoffman, JM (1999). Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology 52, 1166–1173.CrossRefGoogle ScholarPubMed
Keller, MB, Lavori, PW, Mueller, TI, Endicott, J, Coryell, W, Hirschfeld, RM, Shea, T (1992). Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects. Archives of General Psychiatry 49, 809–816.CrossRefGoogle ScholarPubMed
Kosel, M, Schlaepfer, TE (2002). Mechanisms and state of the art of vagus nerve stimulation. Journal of ECT 18, 189–192.CrossRefGoogle ScholarPubMed
Kosel, M, Schlaepfer, TE (2003). Beyond the treatment of epilepsy: new applications of vagus nerve stimulation (VNS) in psychiatry. CNS Spectrums 8, 515–521.CrossRefGoogle ScholarPubMed
Lyketsos, CG, DelCampo, L, Steinberg, M, Miles, Q, Steele, CD, Munro, C, Baker, AS, Sheppard, JM, Frangakis, C, Brandt, J, Rabins, PV (2003). Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Archives of General Psychiatry 60, 737–746.CrossRefGoogle ScholarPubMed
Mann, JJ (2005). The medical management of depression. New England Journal of Medicine 353, 1819–1834.CrossRefGoogle ScholarPubMed
Mason, BL, Pariante, CM (2006). The effects of antidepressants on the hypothalamic–pituitary–adrenal axis. Drug News and Perspectives 19, 603–608.Google ScholarPubMed
Montgomery, SA, Rasmussen, JG, Tanghoj, P (1993). A 24-week study of 20 mg citalopram, 40 mg citalopram, and placebo in the prevention of relapse of major depression. International Clinical Psychopharmacology 8, 181–188.CrossRefGoogle ScholarPubMed
Morris, GL 3rd, Mueller, WM (1999). Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology 53, 1731–1735.CrossRefGoogle Scholar
Naritoku, DK, Terry, WJ, Helfert, RH (1995). Regional induction of fos immunoreactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Research 22, 53–62.CrossRefGoogle ScholarPubMed
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, 1345–1355.CrossRefGoogle ScholarPubMed
Nestler, E (1998). Antidepressant treatments in the 21st century. Biological Psychiatry 44, 526–533.CrossRefGoogle ScholarPubMed
Prudic, J, Sackeim, HA, Devanand, DP (1990). Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Research 31, 287–296.CrossRefGoogle ScholarPubMed
Rush, AJ, George, MS, Sackeim, HA, Marangell, LB, Husain, MM, Giller, C, Nahas, Z, Haines, S, Simpson, RK, Goodmann, R (2000). Vagus nerve stimulation (VNS) for treatment-resistant depression: a multicenter study. Biological Psychiatry 47, 276–286.CrossRefGoogle ScholarPubMed
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 (2005 a). Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biological Psychiatry 58, 347–354.CrossRefGoogle ScholarPubMed
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 (2005 b). Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biological Psychiatry 58, 355–363.CrossRefGoogle ScholarPubMed
Rush, AJ, Trivedi, MH, Wisniewski, SR, Nierenberg, AA, Stewart, JW, Warden, D, Niederehe, G, Thase, ME, Lavori, PW, Lebowitz, BD, McGrath, PJ, Rosenbaum, JF, Sackeim, HA, Kupfer, DJ, Luther, J, Fava, M (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry 163, 1905–1917.CrossRefGoogle ScholarPubMed
Sackeim, HA, Rush, AJ, George, MS, Marangell, LB, Husain, MM, Nahas, Z, Johnson, CR, Seidman, S, Giller, C, Haines, S, Simpson, RK, Goodman, RR (2001). Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25, 713–728.CrossRefGoogle ScholarPubMed
Schachter, SC (2002). Vagus nerve stimulation therapy summary: five years after FDA approval. Neurology 59 (Suppl. 4), S15–S20.CrossRefGoogle ScholarPubMed
Schatzberg, AF, Kraemer, HC (2000). Use of placebo control groups in evaluating efficacy of treatment of unipolar major depression. Biological Psychiatry 47, 736–744.CrossRefGoogle ScholarPubMed
Schlaepfer, TE, Kosel, M (2004). Novel physical treatments for major depression: vagus nerve stimulation, transcranial magnetic stimulation and magnetic seizure therapy. Current Opinion in Psychiatry 17, 15–20.CrossRefGoogle Scholar
Shuchman, M (2007). Approving the vagus-nerve stimulator for depression. New England Journal of Medicine 356, 1604–1607.CrossRefGoogle ScholarPubMed
The Vagus Nerve Stimulation Study Group (1995). A randomized controlled trial of chronic vagus nerve stimulation for treatment of medically intractable seizures. The Vagus Nerve Stimulation Study Group. Neurology 45, 224–230.CrossRefGoogle Scholar
Uthman, BM (2000). Vagus nerve stimulation for seizures. Archives of Medical Research 31, 300–303.CrossRefGoogle ScholarPubMed
Zobel, A, Joe, A, Freymann, N, Clusmann, H, Schramm, J, Reinhardt, M, Biersack, HJ, Maier, W, Broich, K (2005). Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Research 139, 165–179.CrossRefGoogle ScholarPubMed