Aligning the many definitions of treatment resistance in anxiety disorders: A systematic review

Anxiety Disorders often show a chronic course, even when treated with one of the various effective treatments available. Lack of treatment effect could be due to Treatment Resistance (TR). Consensus on a definition for TR Anxiety Disorders (TR‐AD) is highly needed as currently many different operationalizations are in use. Therefore, generalizability in current TR‐AD research is suboptimal, hampering improvement of clinical care. The objective of this review is to evaluate the currently used definitions of TR‐AD by performing a systematic review of available literature. Out of a total of n = 13 042, 62 studies that operationalized TR‐AD were included. The current review confirms a lack of consensus on TR‐AD criteria. In 62.9% of the definitions, TR was deemed present after the first treatment failure. Most studies (93.0%) required pharmacological treatment failures, whereas few (29.0%) required psychological treatment failures. However, criteria for what constitutes “treatment failure” were not provided in the majority of studies (58.1%). Definitions for minimal treatment duration ranged from at least 4 weeks to at least 6 months. Almost half of the TR‐AD definitions (46.8%) required elevated anxiety severity levels in TR‐AD. After synthesis of the results, the consensus definition considers TR‐AD present after both at least one first‐line pharmacological and one psychological treatment failure, provided for an adequate duration (at least 8 weeks) with anxiety severity remaining above a specified threshold. This definition could contribute to improving course prediction and identifying more targeted treatment options for the highly burdened subgroup of TR‐AD patients.