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14


Biological aspects of rapid cycling
and mixed states
Heinz Grunze1 and Jorg Walden2
¨
1
Department of Psychiatry, LMU Munich, Germany
2
Department of Psychiatry, University of Freiburg, Germany




Introduction
Despite the fact that rapid cycling and mixed states are common manifestations of
bipolar 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 traditionally
were exclusion criteria for controlled randomized phase III studies. This changed
just recently, where antiepileptics such as lamotrigine (Calabrese et al., 2000) were
tested for their prophylactic efficacy in rapid-cycling patients. As far as mixed
states 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 generally
excepted definition. The Diagnostic and Statistical Manual of Mental Disorders, 4th
edn (DSM-IV) criteria (fulfillment of all criteria of mania and typical depression at
the same time: American Psychiatric Association, 1994) are too narrow, as it has
been shown in retrospective analysis of the valproate mania study (Bowden et al.,
1994) that one depressive syndrome predicts inferior responsiveness to lithium
and better response to valproate (Swann et al., 1997). A commonly used definition
is the so-called Cincinnati criteria, which require at least three relevant depressive
syndromes (McElroy et al., 1992); however, again, a general consensus on how to
define mixed states has not yet been achieved as other views may also have clinical

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