LAY SUMMARY Posttraumatic stress disorder (PTSD) is a serious mental health condition, and for some individuals, standard treatments such as medication or therapy do not lead to significant improvement. When PTSD remains unresponsive to treatment, it is referred to as treatment-resistant PTSD (TR-PTSD). The goal of this review is to examine how TR-PTSD is defined in the literature and to assess the varying criteria used across studies. The authors analysed 55 research articles that included patients identified as having TR-PTSD. They found considerable variation in how studies defined TR-PTSD, highlighting the lack of a standardized framework. This inconsistency underscores the need for further research to establish clear criteria for defining treatment resistance in PTSD. Developing a well-defined and widely accepted definition of TR-PTSD is essential to improve patient care, guide clinicians in selecting appropriate therapies, and advance research into more effective treatments. Future studies and clinical trials are necessary to refine these definitions and create a standardized model that can be used across research and clinical settings.
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.