Psychometric delineation of the most discriminant symptoms of depressive mixed states

Recent studies have shown that depressive mixed state (DMX), i.e., a major depressive episode (MDE) plus 3 or more intra-MDE hypomanic symptoms, is prevalent in bipolar-II disorder (BP-II) and not uncommon in major depressive disorder (MDD) outpatients. The main aim of the present analyses was to find the most discriminant intra-MDE hypomanic signs and symptoms predicting depressive mixed state. Consecutive 602 MDE outpatients (348 BP-II, 254 MDD) were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of individual intra-MDE hypomanic signs and symptoms for depressive mixed state showed that irritability had a balanced combination of SE, SP, PPV, NPV, and that psychomotor agitation and greater talkativeness had the highest SP and PPV, but lower SE. By virtue of reducing misdiagnoses, SP and PPV are the most important of these tests for clinicians. On the basis of SP and PPV, our results suggest that, though not the most prevalent, irritability (50.3%) and psychomotor agitation (27.7%) represent the most discriminant features of depressive mixed state. Presence of these features should serve as a “red flag” to help clinicians probe more skillfully for the diagnosis of depressive mixed state. Beyond its diagnostic significance, the foregoing signs and symptoms are among the clinical features the FDA lists as presaging “suicidality” on antidepressant monotherapy.