Recent studies showed that depressive mixed state (DMX) (major depressive episode [MDE] with few hypomanic symptoms) was common among depressed outpatients. The aim of the present study was to find a clinicallly useful definition of DMX. A useful definition could be one increasing the probability of making the correct diagnosis of bipolar II. Different definitions of DMX were tested by comparing the sensitivity, specificity, and predictive power for the diagnosis of bipolar H. Three hundred thirty-six consecutive bipolar II (n = 206) and unipolar (n = 130) MDE outpatients were interviewed with the DSM-IV Structured Clinical Interview-Clinician Version (SCID-CV). Different DMX definitions were tested, based on factor analysis, multivariate regression, discriminant analysis, and logistic regression analysis results. The sensitivity, specificity, correctly classified, and receiver operating characteristic (ROC) area for bipolar II diagnosis were compared. Two factors (factor 1, including irritability, psychomotor agitation, and more talkativeness, and factor 2, including racing thoughts, irritability, and distractibility) were significantly associated with bipolar II diagnosis. Of the hypomanic symptoms most common in bipolar II DMX, only irritability and racing thoughts were significantly associated with bipolar II diagnosis on discriminant analysis. DMX with three or more concurrent hypomanic symptoms (DMX3) was strongly associated with bipolar II diagnosis. Comparisons of sensitivity, specificity, correctly classified, and ROC area of the different DMX definitions (factor 1, factor 2, DMX3, irritability during MDE, racing thoughts during MDE) for the diagnosis of bipolar II, showed that factor 1 had the best combination of sensitivity and specificity, high correctly classified and ROC, but DMX3 has the highest specificity, and slightly lower correctly classified and ROC than factor 1. A DMX definition having the highest specificity (DMX3) for bipolar II diagnosis may be more useful to clinicians, leading to few false positives. Bipolar II diagnosis has important treatment and clinical implications, but misdiagnosis is common because diagnosis is often based on history of hypomania (dependent on memory and clinical skills). A cross-sectional marker like DMX3 may increase the probability of making the correct diagnosis of bipolar II, and therefore may be a useful definition of DMX. Copyright 2003, Elsevier Science (USA). All rights reserved.
