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

14Biological aspects of rapid cyclingand mixed states1H einz Grunze and Jörg Walden21 Department of Psychiatry, LMU Munich, Germany2 Department of Psychiatry, University of Freiburg, GermanyIntroductionDespite the fact that rapid cycling and mixed states are common manifestations ofbipolar disorder (Kilzieh and Akiskal, 1999; Akiskal et al., 2000; Grunze et al.,2002a) they have very rarely been subjects of interest for clinical and basic research.As far as clinical research is concerned, rapid cycling and mixed state traditionallywere exclusion criteria for controlled randomized phase III studies. This changedjust recently, where antiepileptics such as lamotrigine (Calabrese et al., 2000) weretested for their prophylactic efficacy in rapid-cycling patients. As far as mixedstates are concerned, recent trials on modern antipsychotics (Keck et al., 2003;Sachs et al., 2002; Tohen et al., 2002) also allowed mixed patients in these studies.A major problem for including mixed states in studies is the lack of a generallyexcepted definition. The Diagnostic and Statistical Manual of Mental Disorders, 4thedn (DSM-IV) criteria (fulfillment of all criteria of mania and typical depression atthe same time: American Psychiatric Association, 1994) are too narrow, as it hasbeen shown in retrospective analysis of the valproate mania study (Bowden et al.,1994) that one depressive syndrome predicts inferior responsiveness to lithiumand better response to valproate (Swann et al., 1997). A commonly used definitionis the so-called Cincinnati criteria, which require at least three relevant depressivesyndromes (McElroy et al., 1992); however, again, a general consensus on how todefine mixed states has not yet been achieved as other views may also have clinicaladvantages (Perugi et al., 1997).The same problem of heterogeneous definitions of mixed state is true for studiestrying to characterize biological differences between mixed patients, manicpatients, and healthy controls. This is also true for rapid-cycling patients. Rapidcycling has been defined by having four or more mood episodes within 1 year. Thisdefinition has been made according to a pivotal trial conducted by Dunner and# Cambridge University Press, 2005.