Kraepelin described in “manic-depressive insanity” (1899/1913) co-ocurrence of opposite polarity symptoms in mania, hypomania, and depression. A full opposite polarity syndrome was not required to diagnose mixed state(s). Actually, mixed state(s) in the official nosology - ICD-1o and DSM-IV - is essentially limited to fullblown mixed state(s) with concomitant syndromal mania and depression. Nevertheless in the past 35 years contributions of Akiskal, Benazzi, and others followed a time of opposition to Krapelin's concept of mixed states - on the part of proeminent psychiatrists, namely: Karl Jaspers and Kurt Scheneider.

To review knowledge about depressive mixed state(s) and its importance in clinical practice.

To emphasize recent evidence supporting clinical and treatment implications of depressive mixed state(s) in both unipolar and bipolar depressed patients.

Sciencedirect and Pubmed search of English-language papers published between January 2000 e September 2010 using and cross-listing key words: bipolar mixed states, depressive mixed state/s, mixed depression, excited depression, agitated depression and suicide.

Recently depressive mixed state(s) was “redefined” and validated as a major depressive episode with some concurrent hypomanic symptoms, its diagnostic validity supported by familiar history and its utility supported by treatment response (negative effects of antidepressants).

No response, worsening and suicidality observed in some depressed patients on antidepressants may reflect the inadequacy of our current oficial nosology which fails to recognize patients for whom antidepressant therapy unprotected by mood stabilizing agents and/or atypical antipsychotics appears to be inappropriate.