Young Mania Rating Scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort.

The aim of this analysis was to identify Young Mania Rating Scale (YMRS) meaningful benchmarks for clinicians (severity threshold, minimal clinically significant difference [MCSD]) using the Clinical Global Impressions Bipolar (CGI-BP) mania scale, to provide a clinical perspective to randomized clinical trials (RCTs) results. We used the cohort of patients with acute manic/mixed state of bipolar disorders (N = 3459) included in the European Mania in Bipolar Longitudinal Evaluation of Medication (EMBLEM) study. A receiver-operating characteristic analysis was performed on randomly selected patients to determine the YMRS optimal severity threshold with CGI-BP mania score ≥ "Markedly ill" defining severity. The MCSD (clinically meaningful change in score relative to one point difference in CGI-BP mania for outcome measures) of YMRS, was assessed with a linear regression on baseline data. At baseline, YMRS mean score was 26.4 (±9.9), CGI-BP mania mean score was 4.8 (±1.0) and 61.7% of patients had a score ≥ 5. The optimal YMRS severity threshold of 25 (positive predictive value [PPV] = 83.0%; negative predictive value [NPV] = 66.0%) was determined. In this cohort, a YMRS score of 20 (typical cutoff for RCTs inclusion criteria) corresponds to a PPV of 74.6% and to a NPV of 77.6%, meaning that the majority of patients included would be classified as severely ill. The YMRS minimal clinically significant difference was 6.6 points.