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R Hamish McAllister-Williams,1,2 Gustavo Alva,3 Michael Banov,4,5 Charles R Conway,6 Cristina Cusin,7 Janetta C De Beer,8 Koen Demyttenaere,9,10 Yoav Domany,11,12 Philippe Domenech,13,14 Darin D Dougherty,7 David L Dunner,15 Kfir Feffer,12,16 Mark S George,17 Dan V Iosifescu,18,19 Erhan Kavakbasi,20,21 Christoph Kraus,22 Fritz-Georg Lehnhardt,23 Paul Lesperance,24 William V McCall,25 James W Murrough,26,27 Ziad Nahas,28 Charles B Nemeroff,29 João Quevedo,30 Christine Reif-Leonhard,31 Patricio Riva-Posse,32 A John Rush,33 Thomas L Schwartz,34 Marthinus P Stander,8 Nolan R Williams35 ,† John Zajecka,36,37 Scott T Aaronson,38 Bernhard T Baune,39– 41 Harold A Sackeim17 1Northern Centre for Mood Disorders, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, UK; 2Cumbria, Northumberland, Tyne and Wear NHS Foundation Trust, Newcastle Upon Tyne, UK; 3ATP Clinical Research, Orange, California, USA; 4PsychAtlanta Research Center/Hightop Health 1012 Coggins Place, Marietta, GA, USA; 5Department of Psychiatry, Medical College of Georgia, Augusta, GA, USA; 6Psychiatry, Washington University in St. Louis, St Louis, MO, USA; 7Psychiatry, Massachusetts General Hospital, Boston, MA, USA; 8VI Research FZ-LLC, Dubai, United Arab Emirates; 9University Psychiatric Center KU Leuven, KU Leuven, Leuven, Belgium; 10Research Group of Psychiatry, Department of Neuroscience, Faculty of Medicine, KU Leuven, Leuven, Belgium; 11Mayanei HaYeshua Medical Center, Bnei Brak, Israel; 12Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; 13Institut de Neuromodulation, Groupe Hospitalo-Universitaire Paris, Psychiatrie et Neurosciences, Université Paris Cité, Paris, France; 14Computational Brain Team, UNICOG, CEA, INSERM, Paris, France; 15Center for Anxiety and Depression, Mercer Island, WA, USA; 16Department of Advanced Therapies, Lev-Hasharon Mental Health Center, Tzur-Moshe, Israel; 17Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA; 18Department of Psychiatry, NYU Grossman School of Medicine, New York, NY, USA; 19Clinical Research Division, Nathan Kline Institute, Orangeburg, NY, USA; 20Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany; 21Department of Psychiatry, University Hospital Münster, University of Münster, Münster, Germany; 22Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria; 23Department of Psychiatry and Psychotherapy, Protestant Hospital Bergisch Gladbach, Bergisch Gladbach, Germany; 24Psychiatric Neuromodulation Unit, Centre Hospitalier de l’Université de Montréal, Université de Montréal, Montréal, Canada; 25Department of Psychiatry and Health Behavior, Medical College of Georgia at Augusta University, Augusta, GA, USA; 26Depression and Anxiety Center for Discovery and Treatment, Icahn School of Medicine Mount Sinai, New York, NY, USA; 27VISN 2 Mental Illness Research, Education, and Clinical Center (MIRECC), James J. Peters VA Medical Center, Bronx NY, NY, USA; 28Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis, MN, USA; 29Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas at Austin, Austin, TX, USA; 30Center for Interventional Psychiatry, Faillace Department of Psychiatry and Behavioral Sciences, McGovern Medical School, the University of Texas Health Science Center at Houston (UTHealth Houston), Houston, TX, USA; 31Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt – Goethe University Frankfurt, Frankfurt Am Main, Germany; 32Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA; 33Department of Psychiatry, Duke-NUS Medical School, Singapore; 34Psychiatry Department, SUNY Upstate Medical University, Syracuse, NY, USA; 35Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA, USA; 36Department of Psychiatry and Behavioral Sciences, Rush University, Chicago, IL, USA; 37Psychiatric Medicine Associates, LLC, Skokie, IL, USA; 38Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Baltimore, MD, USA; 39Department of Psychiatry, University of Münster, Münster, Germany; 40Department of Psychiatry, University of Melbourne, Melbourne, Australia; 41The Florey Institute of Neuroscience and Mental Health, Victoria, Australia†Dr Nolan R Williams passed away on October 8, 2025Correspondence: R Hamish McAllister-Williams, Translational and Clinical Research Institute, Newcastle University, Newcastle Upon Tyne, NE4 5PL, UK, Email hamish.mcallister-williams@newcastle.ac.ukPurpose: Substantial evidence supports the effectiveness of implanted Vagus Nerve Stimulation (VNS) in the management of unipolar difficult-to-treat depression (DTD). While the treatment is included in several national and international guidelines, there is limited information to guide clinicians regarding patient selection and use of VNS in clinical practice.Patients and Methods: A group of 32 experts in the use of VNS were identified from the main countries currently providing the treatment globally. A modified Delphi technique was used to document views on 55 statements regarding the goals, patient selection, and use of VNS treatment in routine clinical practice. Statements were rated on a 9-point Likert scale from “strongly disagree” to “strongly agree”. Over the course of three rounds of voting, with statements modified based on anonymous comments from panelists, consensus agreement or disagreement was deemed if at least 75% of panel members scored a statement between 7 and 9, or 1 and 3, respectively.Results: Consensus was reached by the panel on 75% of the statements covering a wide range of issues. There was agreement that the main goals for VNS are long-term management of symptoms and improvement in quality of life, that the treatment is appropriate for all ages of patients and that there are few contraindications.Conclusion: A set of expert recommendations for the use of VNS for DTD was generated. These should be of value to clinicians to ensure current best practices are followed when considering this treatment.Keywords: vagus nerve stimulation, difficult-to-treat depression, major depressive disorder, consensus, Delphi panel