Which Mixed Depression model? A comparison between DSM-5 - defined mixed features and Koukopoulos' criteria

Background The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition "with mixed features specifier" (DSM-5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component. Objective To compareDSM-5 MFS and Koukopoulos' MxD (KMxD) in terms of prevalence, associated clinical variables and discriminative capacity for bipolar depression in patients with Major Depressive Episode (MDE). Methods 300patients with MDE -155 with major depressive disorder (MDD) and 145 with bipolar disorder (BD) - were recruited. The discriminative capacity of DSM-5 MFS and KMxD criteria for BD was estimated using the Area Under the Curves of Receiver Operating Characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression. Results 44 and 165 patients met the DSM-5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM-5 MFS and KMxD were 77.0% (72.0%-82.1%) and 71.9% (66.2%-77.7%) respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM-5 MFS and ≥3 symptoms (78%/66%) for KMxD. However, considering the DSM-5 MFS cut-off (≥ 3 symptoms), the specificity (97%) increased at the expense of sensitivity (26%). Conclusions KMxD and DSM-5-MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM-5 MFS did not prove to be very inclusive, if compared to the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness.