CNS Drugs

pp 1–13 | Cite as

Mixed States: Modelling and Management

  • Gin S. MalhiEmail author
  • Kristina Fritz
  • Preeya Elangovan
  • Lauren Irwin
Current Opinion


Our current conceptualisation of mixed states, defined as co-occurring manic and depressive symptoms, is unlikely to advance our knowledge or inform clinical practice. Episodes of mixed states can no longer be coded in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and the ‘mixed features specifier’ fails to capture the most common mixed state presentations. This reflects a lack of understanding of both the importance of mixed states and their underlying pathophysiology. Indeed, research into the nature of mixed states is scarce and uninformative, and most clinical practice guidelines fail to provide advice regarding their management. In this paper, we proffer a reconceptualisation of mixed states that provides a framework for informing clinical practice and research. It is based on the ACE model, which deconstructs mood disorders into three domains of symptoms: activity, cognition, and emotion. Symptoms within each domain vary independently over time and in different directions (towards either excitation or inhibition). By deconstructing mood disorders into component domains, mixed states can be explained as the product of different domains varying ‘out of sync’. In most cases, the aetiology of mixed states is unknown. Alongside such idiopathic mixed states, we describe three potential causes of mixed states that are important to consider when formulating management: transitions, ultradian cycling, and treatment-emergent affective switches. In addition to providing guidance on the identification of various kinds of mixed states, we discuss practical strategies for their management, including the monitoring of ACE domains and functioning, to inform the use of psychoeducation and lifestyle changes, psychotherapy, pharmacology, and electroconvulsive therapy.


Compliance with Ethical Standards

Conflict of interest

GSM has received grant or research support from National Health and Medical Research Council, Australian Rotary Health, NSW Health, American Foundation for Suicide Prevention, Ramsay Research and Teaching Fund, Elsevier, AstraZeneca and Servier; has been a speaker for AstraZeneca, Janssen-Cilag, Lundbeck, Otsuka and Servier; and has been a consultant for AstraZeneca, Janssen Cilag, Lundbeck, Otsuka and Servier. KF, PE, and LI have no conflicts of interest that are directly relevant to the content of this article.


No financial support was received for the research, authorship, or publication of this article.


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Authors and Affiliations

  1. 1.Discipline of Psychiatry, Northern Clinical SchoolUniversity of SydneySydneyAustralia
  2. 2.Department of Academic PsychiatryNorthern Syndey Local Health DistrictSt LeonardsAustralia
  3. 3.CADE ClinicRoyal North Shore Hospital, Northern Sydney Local Health DistrictSt LeonardsAustralia
  4. 4.Department of PsychologyCalifornia State UniversityNorthridgeUSA

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