The mixed states as an aspect of the complexity of bipolar disorders

Bipolar disorders are called “bipolar” because we usually consider that they are made of two clinical poles: the depressive one and the manic one. In this perspective a new episode of the disorder is either depressive or manic. Yet things are more complex as depressive symptoms and manic symptoms can be present at the same time. “At the same time” really means simultaneously or in close successive moments, with many alternates between depressive and manic symptoms during the same day. Such clinical states, associating depressive and manic symptoms, are called mixed states. They are considered as important clinical entities having a major impact on the biological theories of affective disorders as they challenge the notion that depression and mania are opposite poles.

The more typical or, as you will understand below, median form of mixed states results from the combination of a full depressive state (a sufficient number of depressive symptoms to deserve the diagnosis of a major depressive episode) and a full manic state (a sufficient number of manic symptoms to deserve the diagnosis of a manic episode). But things are sometimes not so clear-cut and in some cases bipolar mixed states are mainly depressive with less visible or limited hypomanic symptoms (currently we tend to call them mixed depression) or mainly manic with limited depressive symptoms (we call them mixed mania). In fact all the nuances of a rainbow going from pure depression (depression without manic symptoms) to pure mania (mania without depressive symptoms) can be imagined.

Yet an important question remains: what is the nature of mixed states? For instance they can be conceptualized as:
- A transitional state between depression and mania, representing a ‘switch process’ ; in this case all the different states of bipolar disease are on a continuum
- A severe form of mania
- Different entities resulting from the intrusion into a temperament of an opposite affective episode (i.e. the occurrence of a depressive episode in a patient with an hyperthymic/hypomanic temperament or the occurrence of a manic episode in a patient with a depressive temperament)
- A distinct affective state with the superposition of manic and depressive symptoms.

Kraepelin, a famous German psychiatrist from the turn of the XIX and XX centuries, and his pupil Weygandt have proposed another interesting perspective. They suggest different entities resulting from the combination of a bidimensional approach in terms of inhibition and excitation and a segmentation of clinical symptoms into three fields: mood, thought and activity. Between the two poles of pure depression (inhibition in the three fields) and pure mania (excitation in the three fields), there are six other mathematical combinations of excitation and inhibition, proposing six different clinical pictures of mixed states.

One century later this clinical conceptualization proposed by Kraepelin and Weygandt remains appealing for many psychiatrists and clinical scientists from the field. It is probably particularly pertinent for the conceptualization of mixed depression as a state associating inhibition of mood and excitation of thought. Indeed a mixed depression is often mistaken as a pure depression and treated as a pure depression with antidepressants. Even if clinical experts do not agree about the opportunity of stopping or continuing antidepressants when treating mixed depression, all the clinical experts agree about the necessity of using anti-manic medications with or without antidepressants.

The complexity of such clinical states is amplified by their trend to fluctuate and change from one week to another or even from one day to another. For some patients, monitoring these changes on a regular basis and trying to anticipate them is a big challenge. The PSYCHE project, presented on this blog, will try to take up this challenge.

Gilles BERTSCHY and Luisa WEINER
INSERM u666, University Hospital of Strasbourg, University of Strasbourg (F)