Cardiac Effects of Vagus Nerve Stimulation in Patients with Major Depression

Abstract

Introduction: Changes in the heart rate variability are well known among patients with depression. Amongst others, a modulation of the autonomic nervous system is discussed. An investigation of heart rate variability during terms of stimulation could give some insight in the central nervous effect of vagus nerve stimulation (VNS) and possible cardiac side effects.

Methods: The effects of VNS on heart rate (HR) and heart rate variability were studied (HRV) during stimulation in nine patients with major depression according to ICD-10.

Results: When comparing treated depressive patients with a sex- and age-matched healthy control group, the analysis of heart rate revealed significantly (t=2.8; df=16, p=0.012) elevated heart rates during completely switched off conditions, during switched on VNS programme in stimulation-free intervals (5 min period) (t=3.0; p=0.009) and during stimulation conditions (30 s) (t=2.8, Levene corrected, p=0.015). The RMSSD (root mean square of successive differences) as a measure of the HRV increased significantly in switched on conditions during stimulation (30 s) in six patients compared to stimulation-free intervals (t=−4.7; df=5, p=0.006) and baseline.

Discussion: Clinically relevant cardiac effects were not observed throughout the study. VNS induces reversible changes in heart rate variability in patients with major depression during stimulation conditions.

References

• 1 Ben-Menachem E. Vagus-nerve stimulation for the treatment of epilepsy.  Lancet Neurol. 2002;  1 477-482
• 2 Carney RM, Blumenthal JA, Stein PK. et al . Depression, heart rate variability, and acute myocardial infarction.  Circulation. 2001;  104 2024-2028
• 3 Daban C, Martinez-Aran A, Cruz N. et al . Safety and efficacy of vagus nerve stimulation in treatment-resistant depression.  A systematic review. J Affect Disord. 2008;  110 1-15
• 4 Galli R, Limbruno U, Pizzanelli C. et al . Analysis of RR variability in drug-resistant epilepsy patients chronically treated with vagus nerve stimulation.  Auton Neurosci. 2003;  107 52-59
• 5 George MS, Rush AJ, Marangell LB. et al . A one-year comparison of vagus nerve stimulation with treatment as usual for treatment-resistant depression.  Biol Psychiatry. 2005;  58 364-373
• 6 Groves DA, Brown VJ. Vagal nerve stimulation: a review of its applications and potential mechanisms that mediate its clinical effects.  Neurosci Biobehav Rev. 2005;  29 493-500
• 7 Henry TR. Therapeutic mechanisms of vagus nerve stimulation.  Neurology. 2002;  59 S3-14
• 8 Kamphuis MH, Geerlings MI, Dekker JM. et al . Autonomic dysfunction: a link between depression and cardiovascular mortality? The FINE Study.  Eur J Cardiovasc Prev Rehabil. 2007;  14 796-802
• 9 Khaykin Y, Dorian P, Baker B. et al . Autonomic correlates of antidepressant treatment using heart-rate variability analysis.  Can J Psychiatry. 1998;  43 183-186
• 10 Koenig SA, Longin E, Bell N. et al . Vagus nerve stimulation improves severely impaired heart rate variability in a patient with Lennox-Gastaut syndrome.  Seizure. 2008;  17 469-472
• 11 Lederbogen F, Gernoth C, Weber B. et al . Antidepressive treatment with amitriptyline and paroxetine: comparable effects on heart rate variability.  J Clin Psychopharmacol. 2001;  21 238-239
• 12 Mueck-Weymann M, Rechlin T, Ehrengut F. et al . Effects of olanzapine and clozapine upon pulse rate variability.  Depress Anxiety. 2002;  16 93-99
• 13 Nemeroff CB, Mayberg HS, Krahl SE. et al . VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms.  Neuropsychopharmacology. 2006;  31 1345-1355
• 14 Radespiel-Troger M, Rauh R, Mahlke C. et al . Agreement of two different methods for measurement of heart rate variability.  Clin Auton Res. 2003;  13 99-102
• 15 Rechlin T. The effect of amitriptyline, doxepin, fluvoxamine, and paroxetine treatment on heart rate variability.  J Clin Psychopharmacol. 1994;  14 392-395
• 16 Ronkainen E, Korpelainen JT, Heikkinen E. et al . Cardiac autonomic control in patients with refractory epilepsy before and during vagus nerve stimulation treatment: a one-year follow-up study.  Epilepsia. 2006;  47 556-562
• 17 Sackeim HA. The definition and meaning of treatment-resistant depression.  J Clin psychiatry. 2001;  62 ((Suppl 16)) 10-17
• 18 Sackeim HA, Rush AJ, George MS. et al . Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome.  Neuropsychopharmacology. 2001;  25 713-728
• 19 Schlaepfer TE, Frick C, Zobel A. et al . Vagus nerve stimulation for depression: efficacy and safety in a European study.  Psychol Med. 2008;  38 651-661
• 20 Siepmann M, Handel J, Mueck-Weymann M. et al . The effects of moclobemide on autonomic and cognitive functions in healthy volunteers.  Pharmacopsychiatry. 2004;  37 81-87
• 21 Siepmann M, Werner K, Schindler C. et al . The effects of bupropion on heart rate variability in healthy volunteers.  J Clin Psychopharmacol. 2005;  25 283-285
• 22 Sperling W, Reulbach U, Kornhuber J. Clinical benefits and cost effectiveness of vagus nerve stimulation in a long-term treatment of patients with major depression.  Pharmacopsychiatry. 2009;  42 85-88
• 23 Stemper B, Devinsky O, Haendl T. et al . Effects of vagus nerve stimulation on cardiovascular regulation in patients with epilepsy.  Acta Neurol Scand. 2008;  117 231-236
• 24 Zaaimi B, Grebe R, Berquin P. et al . Vagus nerve stimulation therapy induces changes in heart rate of children during sleep.  Epilepsia. 2007;  48 923-930

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