Authors
Manpreet K Singh, Gary Sachs, Jenicka Engler, Ole Andreasen, Montserrat Cosials-Lopez, Rasmus Licht, Mirko Manchia, Luca Pani, Andreas Reif, Eva Reininghaus, Erin Tomaszewski, Eduard Vieta, Robert C Young
Published in
Journal of affective disorders. Pages 122525. Sep 19, 2026. Epub Sep 19, 2026.
Abstract
Reliable measurement of mania is essential for therapeutic development in bipolar disorder (BD). The Young Mania Rating Scale (YMRS) remains the most widely used clinician-rated outcome measure for mania in clinical trials. However, variability in scale administration and interpretation across raters and study sites introduces measurement noise and reduces assay sensitivity. This paper examines contemporary use of the YMRS as a clinical trial endpoint and proposes strategies to improve reliability and standardization.
Members of the International Society of CNS Clinical Trials Methodology and the European College of Neuropsychopharmacology Working Group on Accelerating Development of Psychopathology Measures in BD conducted a methodological review of the YMRS. Drawing on expert consensus, regulatory considerations, and experience from multicenter trials, the group identified key sources of variability in YMRS administration and developed recommendations to improve standardized assessment.
Several factors may affect YMRS reliability, including the absence of a structured interview guide, ambiguity in scoring anchors, item-level inconsistencies, and potential cultural differences in symptom interpretation. Differential weighting of scale items may also influence scoring. Implementation of a structured interview guide and standardized rater training could improve interrater reliability and support more consistent identification and rating of manic symptoms, particularly in multinational trials.
The recommendations are based on expert consensus rather than prospective empirical validation.
The YMRS remains a central outcome measure for mania in BD clinical trials. Greater standardization of administration through a structured interview guide may improve reliability, enhance assay sensitivity, and strengthen endpoint assessment in BD drug development.
PMID:
42762875
Bibliographic data and abstract were imported from PubMed on 20 Sep 2026.
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