Toward a definition of treatment-resistant posttraumatic stress disorder: A systematic review.

Introduction: Posttraumatic stress disorder (PTSD) is a complex disorder that often persists despite the use of evidence-based treatments. This systematic review aims to synthesize existing definitions of treatment-resistant PTSD (TR-PTSD) and examine the criteria used across studies to inform future research and clinical guidelines. Methods: A systematic search was conducted in four databases. Studies were included if they reported on adult participants with TR-PTSD, regardless of definition, or described non-response to one or more treatments. A narrative synthesis was used to categorize findings and suggest refinements to a working TR-PTSD definition. Results: Of 4,046 screened articles, 55 studies met the inclusion criteria. We found substantial variation in how TR-PTSD was defined across studies. Studies investigated pharmacological (n = 19), psychosocial (n = 16), psychedelic-assisted (n = 7), and emerging treatments (n = 13). Findings highlighted diverse intervention strategies. Some reduced PTSD symptoms significantly, and others showed mixed or limited efficacy. Discussion: This study consolidates existing research on TR-PTSD, revealing significant variability in its definitions across studies. The lack of standardized criteria underscores the need for a more consistent framework to guide research and clinical decision-making. The authors propose a dynamic reassessment of treatment resistance that considers adherence, treatment delivery, comorbidities, and mechanisms of action. Future research should incorporate a broader range of treatment response indicators, such as biomarkers and clinical subtypes, to establish a standardized model for TR-PTSD. A clearer definition will improve patient care, aid in therapy selection, and support the development of more effective treatments.