Defining and defying resistance: biomarkers and new treatment avenues in anxiety disorder care
K. Domschke1
1University of Freiburg, Department of Psychiatry, Freiburg, Germany
Background: Treatment resistance in anxiety disorders (TR-AD) constitutes a major clinical challenge, affecting a substantial proportion of patients despite the availability of evidence-based pharmacological and psychotherapeutic interventions.
Aims & Objectives: This talk will present a consensus definition of TR-AD, treatment recommendations for TR-AD and biomarkers potentially informing personalized treatment decisions in TR-AD.
Method: Based on a Delphi method-based consensus process, a clinically useful definition TR-AD will be presented (Domschke et al., 2024). This consensus highlights the importance of exclusion of pseudo-treatment resistance and suggests several criteria for overall treatment resistance (<50% reduction in HAM-A/BAI score, CGI-I score>2) as well as for both pharmacological and psychotherapeutic treatment resistance in particular.
Results: In addition, based on a systematic review the presentation will discuss current state-of-the-art therapeutic options for TR-AD, including optimized pharmacotherapy, psychotherapy, and neuromodulatory interventions such as repetitive transcranial magnetic stimulation (rTMS). Data on augmentation strategies as well as on off-label pharmacological agents (e.g., quetiapine, agomelatine), cannabidiol, ketamine, and compounds currently in clinical development will be summarized (Schiele et al., 2025).
Beyond diagnostic and therapeutic considerations, research on genetic and epigenetic markers associated with treatment response will be presented, highlighting how these biomarkers may guide individualized treatment selection (Domschke et al., 2025).
Discussion & Conclusions: Taken together, this contribution integrates consensus-based diagnostic criteria, innovative therapeutic strategies and biomarker research to advance the understanding and management of treatment resistance in anxiety disorders. It underscores the need for individualized, mechanism-based approaches to enhance treatment outcomes in this underserved patient group.
References:
Domschke, K., Seuling, P. D., Schiele, M. A., Bandelow, B., Batelaan, N. M., Bokma, W. A., Branchi, I., Broich, K., Burkauskas, J., Davies, S. J. C., Dell'Osso, B., Fagan, H., Fineberg, N. A., Furukawa, T. A., Hofmann, S. G., Hood, S., Huneke, N. T. M., Latas, M., Lidbetter, N., Masdrakis, V., McAllister-Williams, R. H., Nardi, A. E., Pallanti, S., Penninx, B., Perna, G., Pilling, S., Pini, S., Reif, A., Seedat, S., Simons, G., Srivastava, S., Steibliene, V., Stein, D. J., Stein, M. B., van Ameringen, M., van Balkom, A., van der Wee, N., Zwanzger, P. & Baldwin, D. S. (2024) The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline. World Psychiatry, 23(1), 113-123. 10.1002/wps.21177.
Domschke, K., Schiele, M. A., Crespo Salvador, O., Zillich, L., Lipovsek, J., Pittig, A., Heinig, I., Ridderbusch, I. C., Straube, B., Richter, J., Hollandt, M., Plag, J., Fydrich, T., Koelkebeck, K., Weber, H., Lueken, U., Dannlowski, U., Margraf, J., Schneider, S., Binder, E. B., Strohle, A., Rief, W., Kircher, T., Pauli, P., Hamm, A., Arolt, V., Hoyer, J., Wittchen, H. U., Erhardt-Lehmann, A., Kottgen, A., Schlosser, P. & Deckert, J. (2025) Epigenetic markers of disease risk and psychotherapy response in anxiety disorders - a longitudinal analysis of the DNA methylome. Mol Psychiatry. 30(10), 4529-4542. 10.1038/s41380-025-03038-5.
Schiele, M. A., Fagan, H., Baldwin, D. S. & Domschke, K. (2025) Integrative systematic review on pharmacological, psychotherapeutic and neurostimulatory treatment options in treatment-resistant anxiety disorders. Psychother Psychosom. doi: 10.1159/000547926
References:
Domschke, K., Seuling, P. D., Schiele, M. A., Bandelow, B., Batelaan, N. M., Bokma, W. A., Branchi, I., Broich, K., Burkauskas, J., Davies, S. J. C., Dell'Osso, B., Fagan, H., Fineberg, N. A., Furukawa, T. A., Hofmann, S. G., Hood, S., Huneke, N. T. M., Latas, M., Lidbetter, N., Masdrakis, V., McAllister-Williams, R. H., Nardi, A. E., Pallanti, S., Penninx, B., Perna, G., Pilling, S., Pini, S., Reif, A., Seedat, S., Simons, G., Srivastava, S., Steibliene, V., Stein, D. J., Stein, M. B., van Ameringen, M., van Balkom, A., van der Wee, N., Zwanzger, P. & Baldwin, D. S. (2024) The definition of treatment resistance in anxiety disorders: a Delphi method-based consensus guideline. World Psychiatry, 23(1), 113-123. 10.1002/wps.21177.
Domschke, K., Schiele, M. A., Crespo Salvador, O., Zillich, L., Lipovsek, J., Pittig, A., Heinig, I., Ridderbusch, I. C., Straube, B., Richter, J., Hollandt, M., Plag, J., Fydrich, T., Koelkebeck, K., Weber, H., Lueken, U., Dannlowski, U., Margraf, J., Schneider, S., Binder, E. B., Strohle, A., Rief, W., Kircher, T., Pauli, P., Hamm, A., Arolt, V., Hoyer, J., Wittchen, H. U., Erhardt-Lehmann, A., Kottgen, A., Schlosser, P. & Deckert, J. (2025) Epigenetic markers of disease risk and psychotherapy response in anxiety disorders - a longitudinal analysis of the DNA methylome. Mol Psychiatry. 30(10), 4529-4542. 10.1038/s41380-025-03038-5.
Schiele, M. A., Fagan, H., Baldwin, D. S. & Domschke, K. (2025) Integrative systematic review on pharmacological, psychotherapeutic and neurostimulatory treatment options in treatment-resistant anxiety disorders. Psychother Psychosom. doi: 10.1159/000547926
In sessions