The concept of mixed state in bipolar disorder: from Kraepelin to DSM-5

Il concetto di stato misto nel disturbo bipolare: da Kraepelin al DSM-5

G. Maina, N. Bertetto, F. Domene Boccolini, G. Di Salvo, G. Rosso, F. Bogetto

Servizio per i Disturbi Depressivi e d’Ansia, Dipartimento di Neuroscienze, Università di Torino


Herein the authors review the most important studies on the conceptualization and diagnosis of bipolar mixed states.


A search in MEDLINE and PUBMED was performed using the following keywords: “bipolar disorder, mixed state/s, mixed episode/s, criteria, validation, mixed mania, dysphoric mania, mixed depression, agitated depression”. Studies on mixed states were reviewed and selected emphasizing historical development, conceptualizations, proposed diagnostic criteria and their validation.


The origin of the concept of affective mixed state can be identified in ancient times. However, the development and systematization of mixed states occurred with the work of Emil Kraepelin and Wilhem Weygandt. After the Kraepelinian era, for several decades mixed states were largely neglected in both research and clinical practice. Even the restrictive criteria of DSM-IV-TR and ICD-10 do not fully account for the variable presentations of bipolar mixed states. Nevertheless, during the last 20 years, many studies have been published on this topic and several authors have proposed and validated less restrictive diagnostic criteria for mixed states.


There is general consensus among clinicians and researchers that DSM-IV-TR and ICD-10 criteria do not capture the complexity of bipolar mixed states. Nevertheless, the debate on the boundaries of mixed states remains open.

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