The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders

Harold A Sackeim,1 Maxine Dibué,2,3 Mark T Bunker,4 A John Rush5– 7 1Departments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; 2Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany;...

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Autores principales:	Sackeim HA, Dibué M, Bunker MT, Rush AJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	vagus nerve stimulation major depressive episode difficult-to-treat depression treatment-resistant depression antidepressant efficacy regulatory process Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/bd9d802dd36f4edd984ae338738fe294
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spelling	oai:doaj.org-article:bd9d802dd36f4edd984ae338738fe2942021-12-02T16:11:14ZThe Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders1178-2021https://doaj.org/article/bd9d802dd36f4edd984ae338738fe2942020-12-01T00:00:00Zhttps://www.dovepress.com/the-long-and-winding-road-of-vagus-nerve-stimulation-challenges-in-dev-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Harold A Sackeim,1 Maxine Dibué,2,3 Mark T Bunker,4 A John Rush5– 7 1Departments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; 2Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany; 3Medical Affairs Europe, LivaNova Deutschland GmbH, Munich, Germany; 4LivaNova USA PLC, Houston, TX, USA; 5Duke-NUS Medical School, Singapore; 6Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; 7Department of Psychiatry, Texas Tech University, Permian Basin, TX, USACorrespondence: Harold A SackeimDepartments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, 2124 Moselem Springs Road, Fleetwood, PA 10522, USATel +1 917 273-5379Email has1@columbia.eduPurpose: The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population.Methods: A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described.Results: Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life.Limitations: Most comparisons of VNS+TAU and TAU were derived from observational, open label studies.Conclusion: The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.Keywords: vagus nerve stimulation, major depressive episode, difficult-to-treat depression, treatment-resistant depression, antidepressant, efficacy, regulatory processSackeim HADibué MBunker MTRush AJDove Medical Pressarticlevagus nerve stimulationmajor depressive episodedifficult-to-treat depressiontreatment-resistant depressionantidepressantefficacyregulatory processNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 3081-3093 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	vagus nerve stimulation major depressive episode difficult-to-treat depression treatment-resistant depression antidepressant efficacy regulatory process Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	vagus nerve stimulation major depressive episode difficult-to-treat depression treatment-resistant depression antidepressant efficacy regulatory process Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Sackeim HA Dibué M Bunker MT Rush AJ The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
description	Harold A Sackeim,1 Maxine Dibué,2,3 Mark T Bunker,4 A John Rush5– 7 1Departments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; 2Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany; 3Medical Affairs Europe, LivaNova Deutschland GmbH, Munich, Germany; 4LivaNova USA PLC, Houston, TX, USA; 5Duke-NUS Medical School, Singapore; 6Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA; 7Department of Psychiatry, Texas Tech University, Permian Basin, TX, USACorrespondence: Harold A SackeimDepartments of Psychiatry and Radiology, Vagelos College of Physicians and Surgeons, Columbia University, 2124 Moselem Springs Road, Fleetwood, PA 10522, USATel +1 917 273-5379Email has1@columbia.eduPurpose: The Vagus Nerve Stimulation (VNS) Therapy System has been studied for more than 20 years in patients with severe, treatment-resistant, chronic mood disorder, i.e., difficult-to-treat depression (DTD). This review distills some of the implications of this research for future therapeutic trials in this population.Methods: A narrative review is provided on VNS in DTD. Protocols for a new, large, sham-controlled trial and a global, longitudinal observational study are described.Results: Following encouraging results in open studies, a randomized, masked, sham-controlled trial of VNS for DTD failed to demonstrate an effect on the primary outcome. The negative results may have been partly due to inadequate treatment duration (10 weeks). In long-term observational studies, adjunctive VNS, combined with treatment-as-usual (VNS+TAU), was administered to more than 1100 DTD patients and compared with TAU alone in more than 400 patients. VNS+TAU had superior antidepressant effects, but maximal symptom reduction was often observed after 12 months or longer of stimulation. VNS+TAU had also marked superiority in durability of benefit. Sustained levels of symptom reduction below the traditional cutoff for response (i.e. < 50%) were associated with improved quality of life.Limitations: Most comparisons of VNS+TAU and TAU were derived from observational, open label studies.Conclusion: The history of VNS in DTD has implications for interventional studies in this population, and perhaps other chronic medical disorders. The slow onset of benefit with VNS necessitates considerably longer controlled observation periods to establish efficacy. Durability of benefit should be routinely incorporated in efficacy assessment. New outcome metrics are needed to both categorically identify clinically meaningful benefit and to integrate information on symptom burden over time.Keywords: vagus nerve stimulation, major depressive episode, difficult-to-treat depression, treatment-resistant depression, antidepressant, efficacy, regulatory process
format	article
author	Sackeim HA Dibué M Bunker MT Rush AJ
author_facet	Sackeim HA Dibué M Bunker MT Rush AJ
author_sort	Sackeim HA
title	The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
title_short	The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
title_full	The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
title_fullStr	The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
title_full_unstemmed	The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders
title_sort	long and winding road of vagus nerve stimulation: challenges in developing an intervention for difficult-to-treat mood disorders
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/bd9d802dd36f4edd984ae338738fe294
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The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders

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