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

Katharina Domschke, Patrik D. Seuling, Miriam A. Schiele, Borwin Bandelow, Neeltje M. Batelaan, Wicher A. Bokma, Igor Branchi, Karl Broich, Julius Burkauskas, Simon J.C. Davies, Bernardo Dell'Osso, Harry Fagan, Naomi Fineberg, Toshi A. Furukawa, Stefan G. Hofmann, Sean Hood, Nathan T.M. Huneke, Milan Latas, Nicky Lidbetter, Vasilios MasdrakisR. Hamish McAllister-Williams, Antonio E. Nardi, Stefano Pallanti, Brenda W.J.H. Penninx, Giampaolo Perna, Steve Pilling, Stefano Pini, Andreas Reif, Soraya Seedat, Gemma Simons, Shrikant Srivastava, Vesta Steibliene, Dan J. Stein, Murray Stein, Michael Van Ameringen, Anton J.L.M. van Balkom, Nic van der Wee, Peter Zwanzger, David S Baldwin

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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.
Original languageEnglish
Pages (from-to)113-123
Number of pages11
JournalWorld Psychiatry: official journal of the World Psychiatric Association (WPA)
Issue number1
Early online date12 Jan 2024
Publication statusPublished - 28 Feb 2024


  • Anxiety disorders
  • agoraphobia
  • consensus guideline
  • evidence-based care
  • generalized anxiety disorder
  • operational criteria
  • panic disorder
  • social anxiety disorder
  • treatment resistance


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