The definition of treatment resistance in anxiety disorders: a Delphi method‐based consensus guideline

Author:

Domschke Katharina1,Seuling Patrik D.1,Schiele Miriam A.1,Bandelow Borwin2,Batelaan Neeltje M.3,Bokma Wicher A.3,Branchi Igor4,Broich Karl5,Burkauskas Julius6,Davies Simon J.C.78,Dell'Osso Bernardo910,Fagan Harry1112,Fineberg Naomi A.13,Furukawa Toshi A.14,Hofmann Stefan G.15,Hood Sean16,Huneke Nathan T.M.1112,Latas Milan1718,Lidbetter Nicky19,Masdrakis Vasilios20,McAllister‐Williams R. Hamish2122,Nardi Antonio E.23,Pallanti Stefano2425,Penninx Brenda W.J.H.3,Perna Giampaolo26,Pilling Steve27,Pini Stefano28,Reif Andreas2930,Seedat Soraya31,Simons Gemma1132,Srivastava Shrikant33,Steibliene˙ Vesta34,Stein Dan J.35,Stein Murray B.36,van Ameringen Michael37,van Balkom Anton J.L.M.3,van der Wee Nic3839,Zwanzger Peter4041,Baldwin David S.111235

Affiliation:

1. Department of Psychiatry and Psychotherapy, Medical Center ‐ University of Freiburg, Faculty of Medicine University of Freiburg Freiburg Germany

2. Department of Psychiatry and Psychotherapy University Medical Center Göttingen Germany

3. Department of Psychiatry and Amsterdam Public Health Research Institute Amsterdam University Medical Center, Vrije Universiteit Amsterdam The Netherlands

4. Center for Behavioral Sciences and Mental Health Istituto Superiore di Sanità Rome Italy

5. Federal Institute for Drugs and Medical Devices Bonn Germany

6. Laboratory of Behavioral Medicine Neuroscience Institute, Lithuanian University of Health Sciences Palanga Lithuania

7. Department of Psychiatry University of Toronto Toronto ON Canada

8. Centre for Addiction and Mental Health Toronto ON Canada

9. Department of Biomedical and Clinical Sciences University of Milan Milan Italy

10. Department of Mental Health and Addictions ASST Fatebenefratelli‐Sacco Milan Italy

11. Clinical and Experimental Sciences, Faculty of Medicine University of Southampton Southampton UK

12. Southern Health NHS Foundation Trust Southampton UK

13. University of Hertfordshire & Hertfordshire Partnership University NHS Foundation Trust Hatfield UK

14. Department of Health Promotion and Human Behavior Kyoto University Graduate School of Medicine/School of Public Health Kyoto Japan

15. Department of Clinical Psychology Philipps University Marburg Marburg Germany

16. Division of Psychiatry Medical School, University of Western Australia Perth WA Australia

17. Clinic for Psychiatry University Clinical Center of Serbia Belgrade Serbia

18. Belgrade University School of Medicine Belgrade Serbia

19. Anxiety UK Manchester UK

20. First Department of Psychiatry Medical School, National and Kapodistrian University of Athens Athens Greece

21. Translational and Clinical Research Institute Newcastle University Newcastle UK

22. Cumbria, Northumberland Tyne & Wear NHS Foundation Trust Newcastle UK

23. Panic & Respiration Laboratory, Institute of Psychiatry Medical School, Federal University of Rio de Janeiro Rio de Janeiro Brazil

24. Institute of Neuroscience Florence Italy

25. Albert Einstein College of Medicine New York NY USA

26. Department of Biological Sciences Humanitas University Milan Italy

27. Centre for Outcomes Research and Effectiveness, Research Department of Clinical, Educational & Health Psychology University College London London UK

28. University of Pisa School of Medicine Pisa Italy

29. Department of Psychiatry, Psychosomatic Medicine and Psychotherapy Goethe University Frankfurt Frankfurt am Main Germany

30. Fraunhofer Institute for Translational Medicine and Pharmacology Frankfurt am Main Germany

31. Department of Psychiatry, Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa

32. Solent NHS Trust Southampton UK

33. Geriatric Mental Health King George's Medical University Lucknow India

34. Neuroscience Institute and Clinic of Psychiatry, Faculty of Medicine Lithuanian University of Health Sciences Kaunas Lithuania

35. South African Medical Research Council Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute University of Cape Town Cape Town South Africa

36. Department of Psychiatry and School of Public Health University of California San Diego San Diego CA USA

37. Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton ON Canada

38. Department of Psychiatry Leiden University Medical Center Leiden The Netherlands

39. Leiden Institute for Brain and Cognition Leiden The Netherlands

40. Clinical Center for Psychiatry, Psychotherapy and Psychosomatic Medicine Kbo‐Inn‐Salzach Hospital Wasserburg am Inn Germany

41. Department of Psychiatry and Psychotherapy Ludwigs‐Maximilians‐University Munich Munich Germany

Abstract

Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment‐resistant anxiety disorders (TR‐AD) informing such trials is currently lacking. We used a Delphi method‐based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR‐AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free‐text responses to a 29‐item questionnaire on relevant aspects of TR‐AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR‐AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR‐AD vs. “difficult‐to‐treat” anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method‐based consensus on operational criteria for TR‐AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence‐based stepped‐care treatment algorithms for patients with anxiety disorders.

Publisher

Wiley

Subject

Psychiatry and Mental health,Pshychiatric Mental Health

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