To review the diagnostic validity and utility of mixed depression, i.e. co-occurrence of depression and manic/hypomanic symptoms.

PubMed search of all English-language papers published between January 1966 and December 2006 using and cross-listing key words: bipolar disorder, mixed states, criteria, utility, validation, gender, temperament, depression-mixed states, mixed depression, depressive mixed state/s, dysphoric hypomania, mixed hypomania, mixed/dysphoric mania, agitated depression, anxiety disorders, neuroimaging, pathophysiology, and genetics. A manual review of paper reference lists was also conducted.

By classic diagnostic validators, the diagnostic validity of categorically-defined mixed depression (i.e. at least 2–3 manic/hypomanic symptoms) is mainly supported by family history (the current strongest diagnostic validator). Its diagnostic utility is supported by treatment response (negative effects of antidepressants). A dimensionally-defined mixed depression is instead supported by a non-bi-modal distribution of its intradepression manic/hypomanic symptoms.

Categorically-defined mixed depression may have some diagnostic validity (family history is the current strongest validator). Its diagnostic utility seems supported by treatment response.