Bipolar Disorders: Mixed States, Rapid-Cycling, and Atypical Forms

23 Beyond major depression and euphoric maniaFamily historyFew systematic data on the family history of patients with mixed states exist.Perugi et al. (1997) did not report any differences in family history betweenpatients with mixed and patients with pure manic states.TreatmentAlthough the data regarding treatment of mixed states are also controversial, thereis a reasonable amount of data suggesting that lithium may be less effective in theshort- and possibly long-term treatment of mixed states than pure mania(Goodwin and Jamison, 1990; McElroy et al., 2000). Valproate, lamotrigine, andpossibly atypical antipsychotics, especially clozapine and olanzapine, may be moreeffective than lithium for patients with mixed episodes. However, the data arebased on studies using different definitions of mixed states, so we need furthercomparative studies. Also, some studies suggest that antidepressant agents mayexacerbate mixed states (Koukopoulos et al., 2000, McElroy et al., 2000; seeChapter 3).Future perspectives on mixed statesAs Perugi and Akiskal have pointed out (see Chapter 2), mixed state does notrepresent a mere superimposition of affective symptoms of opposite polarity, buta complex process of temperamental, affective, and other components – mixedstates might be considered the most eloquent expression of a neurophysiologicaldysregulation.Today, more than 100 years after the publication of the first book on mixedstates by Wilhelm Weygandt in 1899, our understanding of the condition hasincreased, but there are still uncertainties and gaps. What we need is much moreresearch on the topic. What are the major issues in designing such research?* First of all, we need a single consensus, which takes into account the advantagesand disadvantages of broader definitions versus more narrow definitions.* How do we operationalize and assess the boundaries drawn by Kraepelinbetween ‘‘transitional forms’’ (which should represent a stage in betweenwhen depression changes to mania and vice versa) and ‘‘autonomous forms’’(which should mean mixed disorder on its own)?* Once a consensus definition is established, we should be able to clarify some ofthe following points:* What is the gender distribution?* How stable are mixed states over the course of illness?* Are the mixed states a challenge of the bipolar I versus bipolar II dichotomy(a question raised by Vieta et al. in Chapter 4 of this book)?