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The aim of this study was to test different definitions of depressive mixed state (DMX) (major depressive episode (MDE) with some concurrent hypomanic symptoms), to find which one could better define DMX. Unipolar and bipolar II MDE outpatients (n = 168) were interviewed with the DSM-IV Structured Clinical Interview. Depressive mixed state was defined as a MDE with two or more (DMX2), and as a MDE with three or more (DMX3) concurrent hypomanic symptoms. DMX2 was present in 71.8% bipolar II patients, and in 41.5% unipolar (P < 0.01). DMX3 was present in 46.6% of bipolar II, and in 7.6% unipolar patients (P < 0.01). DMX2 and DMX3 had almost the same significant and non-significant associations with study variables (diagnosis, gender, age, age at onset, illness duration, MDE recurrences, axis I comorbidity, MDE severity, depression chronicity, hypomanic, MDE, psychotic, melancholic, and atypical symptoms and features). DMX3 was more strongly associated with bipolar II than DMX2 (odds ratio 10.4 vs 3.5). Findings suggest that DMX3 may be a better definition of DMX due to its stronger association with bipolar II disorder. Findings have important clinical and treatment implications because antidepressants may worsen DMX, and the presence of DMX may induce clinicians to assess systematically and carefully the history of past hypomania.