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

48 G. Perugi and H. S. AkiskalTable 2.3 Cincinnati criteria for mixed mania according to McElroy et al. (1992)A. A full manic syndrome by DSM-IIIR criteriaB. Simultaneous presence of at least three associated depressive symptomsC. Simultaneous presence is defined as manic and depressive symptoms occurring at the sametime or alternating extremely rapidly, within minutesD. Manic and depressive symptoms are simultaneously present for at least 24 hDSM-IIR, Diagnostic and Statistical Manual of Mental Disorders, 3rd edn revised (AmericanPsychiatric Association, 1987).conforms to the concept of dysphoric mania, i.e., mania plus at least three nonmanicdepressive symptoms. Utilizing this definition, some distinctive features ofmixed mania compared with pure mania have been found: greater prevalence infemales, more past MS episodes, higher probability of an MS at onset, and higherrate of comorbidity with obsessive-compulsive disorder (McElroy et al., 1995).A similar definition of MS was used in the clinical Epidemiology of Mania(EPIMAN) study, which was conducted in four centers in France, involvingover 100 patients (Akiskal et al., 1998). Because patients were entered into thestudy on the basis of meeting full criteria for index manic episodes, the rates forstrictly defined DSM-IV mixed states were low (6.7%). But using a cut-off oftwo or more depressive symptoms, 37% could be characterized as dysphoricmanic. As expected, these patients scored more than 10 on the modifiedHamilton-D (HAM-D) scale. Depressed moodandsuicidalthoughtshadthebest predictive diagnostic value for mixed mania. An important finding of thisstudywasthatmixedmanicpatients,comparedwiththosewithpuremania,had a higher percentage of depressive temperamental traits. Such data arguethat mixed mania can be defined categorically by two or more depressivesymptoms, psychometrically on the basis of HAM-D > 10, or dimensionallyon the basis of depressive (dysthymic) temperamental traits. The latter findingsupports the hypothesis that MSs arise when an affective episode is superimposedon a temperament of opposite polarity (Akiskal, 1992). Data alongthese lines have also been reported in the Pisa–San Diego collaborative study(Perugi et al., 1997, to be more fully discussed later in this chapter) and the Hallestudy (Brieger et al., 2003).The optimum number of depressive symptoms during mania in characterizingMS has varied in the literature. McElroy et al. (1992) proposedacut-offof53,Akiskal et al. (1998) 52, and Swann et al. (1997) 51 depressive symptoms inthe midst of mania for the diagnosis of MS. Defining this cut-off is not a merenosological exercise, because even one depressive symptom during mania seems topredict low response to lithium and good response to divalproex (Swann et al., 1997).