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

377 Investigational strategiesTable 17.1 Counting phase shiftsPrevious assigned mood stateCurrent mood stateDepression Hypomania Mania MixedDepression No phase shift Yes Yes No phase shiftHypomania Yes No phase shift No phase shift No phase shiftMania Yes No phase shift No phase shift No phase shiftMixed Yes Yes Yes No phase shiftinvestigators to develop clear operational procedures that can be applied consistentlyby raters at multiple sites.Standardized assessment tools for prospective longitudinal follow-up may offeradvantages over retrospective assessments like LIFE. The advantages of prospectiverating may be particularly important when attempting to track multiple brieffluctuations in mood state.Defining a phase of illness is a key research need. Kramlinger and Post (1996)defined an alternative to the DSM episode definitions of ultrarapid cycling toaccount for phase shifts that occur within a 24-h period. The 15-point Bunney-Hamburg Rating Scale, administered twice daily by nurses, was used to identify aphase shift. Subjects also marked 100-mm visual analogue lines, where the left sidewas anchored by ‘‘best ever’’ (manic) and the right side by ‘‘worst ever’’ (depressed).A new depressive episode was defined as a sudden increase of three points in theassessment score or at least 7 days with a depression rating greater than 7. The end ofthe depressive episode was determined by a sudden decrease of 3–6 points, asustained period of at least 7 days with a score less than five, or a switch in polarityfrom depression to mania.There are some obvious problems with this technique: a patient who was alreadyin a major depressive episode could experience several brief depressions due totransient three-point fluctuations in the course of a single day. Perhaps moreimportant than the technical issues is the fact that patients are typically notobserved in inpatient units while undergoing treatment for rapid cycling. Inorder for a trial to target rapid cycling effectively, it would need to take placeover a period of 6 months or more. Outcome measures that rely on trainedobserver ratings are impractical, because subjects are not likely to remain hospitalizedfor the long periods required to assess multiple episodes.Methods developed in our clinic for counting phases can be more readilyapplied to outpatient studies. Phase changes are defined as the appearance ofa new mood state with duration of 48 h (Table 17.1). If the new mood state isnot sustained for 48 h, it must meet the DSM-IV criteria for an episode. This