Vagusnervstimulation (VNS) als Behandlungsoption für Depressionen

Zusammenfassung

Einführung Depressionen sind häufig und zeigen bei einem Drittel der Fälle einen therapieresistenten und chronifizierten Verlauf. Die invasive Vagusnervstimulation (VNS) ist eine langfristige Zusatzbehandlungsoption, die in den letzten Jahren zunehmend häufig angewandt wird. Eine CE-Zertifizierung für die Behandlung der chronischen und therapierefraktären Depression besteht seit 2001. Methoden Basierend auf einer systematischen Literaturrecherche geben wir in diesem narrativen Review einen Überblick mit klinischem Schwerpunkt über die invasive VNS als Behandlungsoption bei der Depressionen. Ergebnisse Nach psychiatrischer Indikationsstellung und Aufklärung wird in einem kurzen operativen Eingriff der Impulsgeber im Bereich der linken Brust implantiert. Die Einstellung der Stimulationsparameter erfolgt ambulant-psychiatrisch in den ersten Wochen nach der OP. Das VNS-System wird zunächst in 3-, später in 6-monatigen Intervallen kontrolliert. Die Stimulation erfolgt für 30 Sekunden zwischen 5-minütigen Intervallen. Stimulationssynchrone Heiserkeit ist die häufigste Nebenwirkung. Steigerung noradrenerger und serotonerger Transmission im Gehirn und anti-inflammatorische Effekte werden als Wirkmechanismen diskutiert. Der Behandlungseffekt tritt verzögert nach 6–12 Monaten ein. Die kumulative Responserate nach 5 Jahren liegt für die VNS plus Standardbehandlung bei ca. 67,6% im Vergleich zu 40.9% bei Standardbehandlung ohne VNS. Langfristige positive Effekte auf Lebensqualität, Kognition, Morbidität und Mortalität wurden beschrieben. Schlussfolgerung Die VNS ist eine langfristige, sichere Behandlungsoption bei schwer betroffenen Depressionspatienten mit positivem Effekt auf Symptomschwere, Lebensqualität und kognitive Funktion.

Abstract

Major depressive disorder is a common mental health disease with a chronic and treatment-resistant course in about one-third of patients. Invasive vagus nerve stimulation (VNS) as a long-term adjunctive treatment option has increasingly been used in the last years. VNS was CE-certified in the European Union for use in chronic and treatment-resistant depression in 2001. Method In this narrative literature review we provide an overview on VNS as a treatment option in patients with depression. We particularly focus on aspects with high clinical relevance. Results Indication to conduct VNS is determined after comprehensive evaluation of the patients’ symptoms and psychiatric history. After education of patients and caregivers and obtaining informed consent, a pacemaker-like pulse generator is implanted in the left chest in a short surgical procedure. In the first weeks after implantation, the stimulation is turned on stepwise in an outpatient setting. The left vagal nerve is stimulated for 30 sec. every 5 minutes. Hoarseness during stimulation is the most frequent side-effect. There is a delay in the onset of antidepressant action of about 6–12 months. In a large registry, the cumulative response rate after 5 years was significantly higher (67.6%) in patients treated with VNS plus treatment-as-usual (TAU) than TAU alone (40.9%). Long-term benefits of VNS on quality of life, cognition, morbidity and mortality have been described previously. Conclusion VNS is a long-term safe treatment option in severely affected patients with depression with positive impact on depression severity, quality of life and cognitive function. Increase of monoaminergic transmission and anti-inflammatory effects of VNS are possible mechanisms of action.

Schlüsselwörter

Vagusnervstimulation - VNS - therapieresistente Depression - schwer behandelbare Depression - DTD - difficult-to-treat depression

Key words

Vagusnerve stimulation - VNS - TRD - DTD - difficult-to-treat depression - treatment-resistant depression

Publication History

Received: 10 February 2023

Accepted: 31 August 2023

Article published online:
13 November 2023

• Literatur

• 1 Malhi GS, Mann JJ. Depression. Lancet Lond Engl 2018; 392: 2299-2312 DOI: 10.1016/S0140-6736(18)31948-2.
• 2 AEZQ. Nationale VersorgungsLeitlinie Unipolare Depression. 2022 Version 3.0. 2022;
• 3 Gaynes BN, Lux L, Gartlehner G. et al. Defining treatment-resistant depression. Depress Anxiety 2020; 37: 134-145 DOI: 10.1002/da.22968.
• 4 Seemüller F, Kolter M, Musil R. et al. Chronic vs non-chronic depression in psychiatric inpatient care – Data from a large naturalistic multicenter trial. J Affect Disord 2022; 299: 73-84 DOI: 10.1016/j.jad.2021.11.042.
• 5 McAllister-Williams RH, Arango C, Blier P. et al. The identification, assessment and management of difficult-to-treat depression: An international consensus statement. J Affect Disord 2020; 267: 264-282 DOI: 10.1016/j.jad.2020.02.023.
• 6 Berensmann M, Gratzfeld M. [Requirements for CE-marking of apps and wearables]. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 2018; 61: 314-320 DOI: 10.1007/s00103-018-2694-2.
• 7 Kraus C, Quach D, Sholtes DM. et al. Setting Up a Successful Vagus Nerve Stimulation Service for Patients With Difficult-to-Treat Depression. Neuromodulation J Int Neuromodulation Soc 2022; 25: 316-326 DOI: 10.1016/j.neurom.2021.12.010.
• 8 Reif-Leonhard C, Reif A, Baune BT. et al. [Vagus nerve stimulation for difficult to treat depression]. Nervenarzt 2022; 93: 921-930 DOI: 10.1007/s00115-022-01282-6.
• 9 Toffa DH, Touma L, El Meskine T. et al. Learnings from 30 years of reported efficacy and safety of vagus nerve stimulation (VNS) for epilepsy treatment: A critical review. Seizure 2020; 83: 104-123 DOI: 10.1016/j.seizure.2020.09.027.
• 10 Elger G, Hoppe C, Falkai P. et al. Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res 2000; 42: 203-210 DOI: 10.1016/s0920-1211(00)00181-9.
• 11 Giordano F, Zicca A, Barba C. et al. Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity. Epilepsia 2017; 58: 85-90 DOI: 10.1111/epi.13678.
• 12 Marangell LB, Rush AJ, George MS. et al. Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry 2002; 51: 280-287 DOI: 10.1016/s0006-3223(01)01343-9.
• 13 Sackeim HA, Rush AJ, George MS. et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacol Off Publ Am Coll Neuropsychopharmacol 2001; 25: 713-728 DOI: 10.1016/S0893-133X(01)00271-8.
• 14 Rush AJ, Marangell LB, Sackeim HA. et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 2005; 58: 347-354 DOI: 10.1016/j.biopsych.2005.05.025.
• 15 Aaronson ST, Sears P, Ruvuna F. et al. A 5-Year Observational Study of Patients With Treatment-Resistant Depression Treated With Vagus Nerve Stimulation or Treatment as Usual: Comparison of Response, Remission, and Suicidality. Am J Psychiatry 2017; 174: 640-648 DOI: 10.1176/appi.ajp.2017.16010034.
• 16 Aaronson ST, Goldwaser EL, Kutzer DJ. et al. Vagus Nerve Stimulation in Patients Receiving Maintenance Therapy With Electroconvulsive Therapy: A Series of 10 Cases. J ECT 2021; 37: 84-87 DOI: 10.1097/YCT.0000000000000724.
• 17 Conway CR, Kumar A, Xiong W. et al. Chronic Vagus Nerve Stimulation Significantly Improves Quality of Life in Treatment-Resistant Major Depression. J Clin Psychiatry 2018; 79: 18m12178 DOI: 10.4088/JCP.18m12178.
• 18 Desbeaumes Jodoin V, Richer F, Miron J-P. et al. Long-term Sustained Cognitive Benefits of Vagus Nerve Stimulation in Refractory Depression. J ECT 2018; 34: 283-290 DOI: 10.1097/YCT.0000000000000502.
• 19 Dusi V, De Ferrari GM. Vagal stimulation in heart failure. Herz 2021; 46: 541-549 DOI: 10.1007/s00059-021-05076-5.
• 20 Gelenberg AJ, Freeman MP, Markowitz JC. et al. Practice Guideline For The Treatment of Patients With Major Depressive Disorder. 2010
• 21 Milev RV, Giacobbe P, Kennedy SH. et al. 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 Rev Can Psychiatr 2016; 61: 561-575 DOI: 10.1177/0706743716660033.
• 22 Berry SM, Broglio K, Bunker M. et al. A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression. Med Devices Auckl NZ 2013; 6: 17-35 DOI: 10.2147/MDER.S41017.
• 23 LivaNova. VNS TherapyTM System Depression Physician’s Manual, US Version. For Healthcare Professionals.. 2022 2022.
• 24 Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol 2016; 594: 5781-5790 DOI: 10.1113/JP271539.
• 25 Bonaz B, Sinniger V, Pellissier S. The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Front Immunol 2017; 8: 1452 DOI: 10.3389/fimmu.2017.01452.
• 26 Johnson KV-A, Steenbergen L. Gut Feelings: Vagal Stimulation Reduces Emotional Biases. Neuroscience 2022; 494: 119-131 DOI: 10.1016/j.neuroscience.2022.04.026.
• 27 Ruffoli R, Giorgi FS, Pizzanelli C. et al. The chemical neuroanatomy of vagus nerve stimulation. J Chem Neuroanat 2011; 42: 288-296 DOI: 10.1016/j.jchemneu.2010.12.002.
• 28 Grimonprez A, Raedt R, Portelli J. et al. The antidepressant-like effect of vagus nerve stimulation is mediated through the locus coeruleus. J Psychiatr Res 2015; 68: 1-7 DOI: 10.1016/j.jpsychires.2015.05.002.
• 29 Dorr AE, Debonnel G. Effect of vagus nerve stimulation on serotonergic and noradrenergic transmission. J Pharmacol Exp Ther 2006; 318: 890-898 DOI: 10.1124/jpet.106.104166.
• 30 Biggio F, Gorini G, Utzeri C. et al. Chronic vagus nerve stimulation induces neuronal plasticity in the rat hippocampus. Int J Neuropsychopharmacol 2009; 12: 1209-1221 DOI: 10.1017/S1461145709000200.
• 31 Fornaro R, Actis GC, Caviglia GP. et al. Inflammatory Bowel Disease: Role of Vagus Nerve Stimulation. J Clin Med 2022; 11: 5690 DOI: 10.3390/jcm11195690.
• 32 Breit S, Kupferberg A, Rogler G. et al. Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry 2018; 9: 44 DOI: 10.3389/fpsyt.2018.00044.
• 33 Borovikova LV, Ivanova S, Zhang M. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 2000; 405: 458-462 DOI: 10.1038/35013070.
• 34 O’Keane V, Dinan TG, Scott L. et al. Changes in hypothalamic-pituitary-adrenal axis measures after vagus nerve stimulation therapy in chronic depression. Biol Psychiatry 2005; 58: 963-968 DOI: 10.1016/j.biopsych.2005.04.049.
• 35 Conway CR, Sheline YI, Chibnall JT. et al. Cerebral blood flow changes during vagus nerve stimulation for depression. Psychiatry Res 2006; 146: 179-184 DOI: 10.1016/j.pscychresns.2005.12.007.
• 36 Kosel M, Brockmann H, Frick C. et al. Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex. Psychiatry Res 2011; 191: 153-159 DOI: 10.1016/j.pscychresns.2010.11.004.
• 37 Perini GI, Toffanin T, Pigato G. et al. Hippocampal Gray Volumes Increase in Treatment-Resistant Depression Responding to Vagus Nerve Stimulation. J ECT 2017; 33: 160-166 DOI: 10.1097/YCT.0000000000000424.
• 38 Conway CR, Chibnall JT, Gebara MA. et al. Association of cerebral metabolic activity changes with vagus nerve stimulation antidepressant response in treatment-resistant depression. Brain Stimulat 2013; 6: 788-797 DOI: 10.1016/j.brs.2012.11.006.
• 39 Kavakbasi E, Gross J, Wollbrink A. et al. Acute effect of vagus nerve stimulation (VNS) on brain function. J Psychiatr Res 2021; 141: 136-139 DOI: 10.1016/j.jpsychires.2021.06.042.
• 40 McAllister-Williams RH, Bulmer S, Newton K. et al. Assessment for vagus nerve stimulation in patients with difficult-to-treat depression: a model from the Newcastle Regional Affective Disorders Service (RADS). J Affect Disord 2021; 280: 315-318 DOI: 10.1016/j.jad.2020.11.020.