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J Affect Disord. 2015 May 1;176:18-23. doi: 10.1016/j.jad.2015.01.053. Epub 2015 Feb 4.

Depressive mixed states: A reappraisal of Koukopoulos' criteria.

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Lucio Bini Mood Disorders Center, New York, NY, United States; New York University Medical Center & Child Study Center, New York, NY, United States; International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA, United States.
Lucio Bini Mood Disorders Center, New York, NY, United States. Electronic address:
Centro Lucio Bini, Rome, Italy.



Mixed states have been a fundamental part of Kraepelin׳s conceptualization of the manic-depressive illness. However, after Kraepelin, the study of mixed states was not of great interest, until the publication of the RDC criteria (1978) and then the DSM-III edition (1980), where criteria for mixed manic states were operationalized. The most notable victims of DSM nosology were depressive mixed states, in particular depression with flight of ideas and excited (agitated) depression.


We briefly review the clinical work of Athanasios Koukopoulos on depressive mixed states (in particular agitated depression) pointing out the diagnostic and therapeutic contributions, especially in the lights of Koukopoulos׳ first description of depressive mixed syndrome in 1992.


The mixed depressive syndrome is not a transitory state but a state of long duration, which may last weeks or several months. The clinical picture is characterized by dysphoric mood, emotional lability, psychic and/or motor agitation, talkativeness, crowded and/or racing thoughts, rumination, initial or middle insomnia. Impulsive suicidal attempts may be frequent. The family observes incessant complaints, irritability, occasional verbal outbursts, occasional physical aggression, and occasional hypersexuality. Treatment with antipsychotics and ECT is very effective; antidepressants can worsen the clinical picture.


Selective but not systematic review of the literature on depressive mixed states. Relatively little research data is currently available for validation of the criteria proposed by Koukopoulos.


Koukopoulos׳ proposal of mixed depression, besides its diagnostic implications, clearly identifying it as manifestations of bipolar disorder, allows for better clinical characterization of cases and improves treatment decisions.


Agitated depression; Bipolar disorder; Mixed depression; Mixed mania; Mixed states

[Indexed for MEDLINE]

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