Outcome definitions such as response, remission, non-response, and treatment resistance are central to the evaluation of pharmacological trials in posttraumatic stress disorder (PTSD). Yet, definitional heterogeneity complicates evidence synthesis and clinical translation.

This methodological systematic review identified and classified how these outcome constructs have been defined and used in randomized controlled trials (RCTs) of pharmacological treatments for PTSD and examined variation in these definitions according to study characteristics, including publication period, intervention class, population type, instrument version, role within the trial, and treatment approach.

A systematic search was conducted without language restrictions in MEDLINE, CENTRAL, Embase, and PsycINFO, from inception to 1st August 2026, following a preregistered protocol (PROSPERO CRD420251074957). Eligible studies were RCTs evaluating pharmacological interventions for PTSD that reported at least one definition of treatment response, remission, non-response, or treatment resistance. At least two reviewers independently screened studies, extracted data and assessed Risk of Bias using the Cochrane RoB-1 tool.

Definitions of response and remission varied considerably across the 111 included RCTs, with some variation reflecting changes in assessment instruments and diagnostic systems over time. The most frequently used response criterion was a CGI I/C rating of 1 or 2, indicating “very much improved” or “much improved”. A ≥ 30% reduction in CAPS score was repeatedly used across DSM-III-, DSM-IV-, and DSM-5-based CAPS versions, although alternative percentage thresholds, absolute score decreases, and composite definitions were common. Remission definitions differed more clearly by instrument generation: earlier CAPS generations predominantly used absolute CAPS endpoint thresholds, particularly scores around 20, whereas DSM-5 studies more often incorporated loss of PTSD diagnostic status. Treatment resistance or non-response was typically defined by prior treatment failure, but adequacy criteria, defined as minimum requirements regarding treatment type, dose, and duration of prior interventions, were rarely specified and varied substantially. After exclusion of studies using treatment-resistance only descriptively, adequacy criteria were specified more frequently, but heterogeneity in the number and type of required treatment failures persisted.

Definitions of response, remission, non-response and treatment resistance varied widely across pharmacological PTSD RCTs. This variability complicates comparisons across studies, may alter pooled responder estimates and contribute to between-study heterogeneity, hindering efforts to synthesize evidence. Standardized, consensus-based definitions are needed to improve the interpretability and comparability of future research and its relevance to clinical practice.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.