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

  • T. E. Schlaepfer (a1) (a2) (a3), C. Frick (a1) (a2), A. Zobel (a2), W. Maier (a2), I. Heuser (a4), M. Bajbouj (a4), V. O'Keane (a5), C. Corcoran (a5), R. Adolfsson (a6), M. Trimble (a7), H. Rau (a8) (a9), H.-J. Hoff (a8), F. Padberg (a10), F. Müller-Siecheneder (a10), K. Audenaert (a11), D. Van den Abbeele (a11), K. Matthews (a12), D. Christmas (a12), Z. Stanga (a1) and M. Hasdemir (a13)...
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.

Copyright
Corresponding author
*Address for correspondence: T. E. Schlaepfer, M.D., Department of Psychiatry/University Hospital, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany. (Email: schlaepf@jhmi.edu)
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This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

JM Andrews , CB Nemeroff (1994). Contemporary management of depression. American Journal of Medicine 97, 24S32S.

E Ben-Menachem (2001). Vagus nerve stimulation, side effects, and long-term safety. Journal of Clinical Neurophysiology 18, 415418.

E Ben-Menachem , R Manon-Espaillat , R Ristanovic , BJ Wilder , H Stefan , W Mirza , WB Tarver , JF Wernicke (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, 616626.

LL Carpenter , FA Moreno , MA Kling , GM Anderson , WT Regenold , DM Labiner , LH Price (2004). Effect of vagus nerve stimulation on cerebrospinal fluid monoamine metabolites, norepinephrine, and gamma-aminobutyric acid concentrations in depressed patients. Biological Psychiatry 56, 418426.

JH Chae , Z Nahas , M Lomarev , S Denslow , JP Lorberbaum , DE Bohning , MS George (2003). A review of functional neuroimaging studies of vagus nerve stimulation (VNS). Journal of Psychiatric Research 37, 443455.

CR Conway , YI Sheline , JT Chibnall , MS George , JW Fletcher , MA Mintun (2006). Cerebral blood flow changes during vagus nerve stimulation for depression. Psychiatry Research 146, 179184.

P Dago , F Quitkin (1995). Role of the placebo response in the treatment of depressive disorders. CNS Drugs 4, 335340.

AE Dorr , G Debonnel (2006). Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. Journal of Pharmacology and Experimental Therapeutics 318, 890898.

D Dunner , A Rush , J Russell , M Burke , S Woodard , P Wingard , J Allen (2006). Prospective, long-term, multicenter study of the naturalistic outcomes of patients with treatment-resistant depression. Journal of Clinical Psychiatry 67, 688695.

G Elger , C Hoppe , P Falkai , A Rush , C Elger (2000). Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Research 42, 203210.

MS George , AJ Rush , LB Marangell , HA Sackeim , SK Brannan , SM Davis , R Howland , MA Kling , F Moreno , B Rittberg , D Dunner , T Schwartz , L Carpenter , M Burke , P Ninan , P Goodnick (2005). A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression. Biological Psychiatry 58, 364373.

MS George , HA Sackeim , AJ Rush , LB Marangell , Z Nahas , MM Husain , S Lisanby , T Burt , J Goldman , JC Ballenger (2000). Vagus nerve stimulation: a new tool for brain research and therapy. Biological Psychiatry 47, 287295.

DA Groves , VJ Brown (2005). Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects. Neuroscience and Biobehavioral Reviews 29, 493500.

M Hamilton (1967). Development of a rating scale for primary depressive illness. British Journal of Social and Clinical Psychology 6, 278296.

A Handforth , C DeGiorgio , S Schachter , B Uthman , D Naritoku , E Tecoma (1998). Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial. Neurology 51, 4855.

CL Harden , MC Pulver , LD Ravdin , B Nikolov , JP Halper , DR Labar (2000). A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy and Behavior 1, 9399.

C Helmstaedter , C Hoppe , CE Elger (2001). Memory alterations during acute high-intensity vagus nerve stimulation. Epilepsy Research 47, 3742.

TR Henry , JR Votaw , PB Pennell , CM Epstein , RAE Bakay , TL Faber , ST Grafton , JM Hoffman (1999). Acute blood flow changes and efficacy of vagus nerve stimulation in partial epilepsy. Neurology 52, 11661173.

MB Keller , PW Lavori , TI Mueller , J Endicott , W Coryell , RM Hirschfeld , T Shea (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, 809816.

M Kosel , TE Schlaepfer (2002). Mechanisms and state of the art of vagus nerve stimulation. Journal of ECT 18, 189192.

M Kosel , TE Schlaepfer (2003). Beyond the treatment of epilepsy: new applications of vagus nerve stimulation (VNS) in psychiatry. CNS Spectrums 8, 515521.

CG Lyketsos , L DelCampo , M Steinberg , Q Miles , CD Steele , C Munro , AS Baker , JM Sheppard , C Frangakis , J Brandt , PV Rabins (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, 737746.

JJ Mann (2005). The medical management of depression. New England Journal of Medicine 353, 18191834.

BL Mason , CM Pariante (2006). The effects of antidepressants on the hypothalamic–pituitary–adrenal axis. Drug News and Perspectives 19, 603608.

SA Montgomery , JG Rasmussen , P Tanghoj (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, 181188.

GL Morris 3rd, WM Mueller (1999). Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy. The Vagus Nerve Stimulation Study Group E01-E05. Neurology 53, 17311735.

DK Naritoku , WJ Terry , RH Helfert (1995). Regional induction of fos immunoreactivity in the brain by anticonvulsant stimulation of the vagus nerve. Epilepsy Research 22, 5362.

CB Nemeroff , HS Mayberg , SE Krahl , J McNamara , A Frazer , TR Henry , MS George , DS Charney , SK Brannan (2006). VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms. Neuropsychopharmacology 31, 13451355.

E Nestler (1998). Antidepressant treatments in the 21st century. Biological Psychiatry 44, 526533.

J Prudic , HA Sackeim , DP Devanand (1990). Medication resistance and clinical response to electroconvulsive therapy. Psychiatry Research 31, 287296.

AJ Rush , MS George , HA Sackeim , LB Marangell , MM Husain , C Giller , Z Nahas , S Haines , RK Simpson , R Goodmann (2000). Vagus nerve stimulation (VNS) for treatment-resistant depression: a multicenter study. Biological Psychiatry 47, 276286.

AJ Rush , LB Marangell , HA Sackeim , MS George , SK Brannan , SM Davis , R Howland , MA Kling , BR Rittberg , WJ Burke , MH Rapaport , J Zajecka , AA Nierenberg , MM Husain , D Ginsberg , RG Cooke (2005 a). Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biological Psychiatry 58, 347354.

AJ Rush , MH Trivedi , SR Wisniewski , AA Nierenberg , JW Stewart , D Warden , G Niederehe , ME Thase , PW Lavori , BD Lebowitz , PJ McGrath , JF Rosenbaum , HA Sackeim , DJ Kupfer , J Luther , M Fava (2006). Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. American Journal of Psychiatry 163, 19051917.

HA Sackeim , AJ Rush , MS George , LB Marangell , MM Husain , Z Nahas , CR Johnson , S Seidman , C Giller , S Haines , RK Simpson , RR Goodman (2001). Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology 25, 713728.

SC Schachter (2002). Vagus nerve stimulation therapy summary: five years after FDA approval. Neurology 59 (Suppl. 4), S15S20.

AF Schatzberg , HC Kraemer (2000). Use of placebo control groups in evaluating efficacy of treatment of unipolar major depression. Biological Psychiatry 47, 736744.

TE Schlaepfer , M Kosel (2004). Novel physical treatments for major depression: vagus nerve stimulation, transcranial magnetic stimulation and magnetic seizure therapy. Current Opinion in Psychiatry 17, 1520.

M Shuchman (2007). Approving the vagus-nerve stimulator for depression. New England Journal of Medicine 356, 16041607.

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, 224230.

BM Uthman (2000). Vagus nerve stimulation for seizures. Archives of Medical Research 31, 300303.

A Zobel , A Joe , N Freymann , H Clusmann , J Schramm , M Reinhardt , HJ Biersack , W Maier , K Broich (2005). Changes in regional cerebral blood flow by therapeutic vagus nerve stimulation in depression: an exploratory approach. Psychiatry Research 139, 165179.

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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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