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

382 G. Sachs and M. GravesDemonstration of decreased cycle rates might be possible using the continuousphasecounting strategy above or using the categorical determination of zero, one,or more than one phase change to compare the percentage of months with zerophase changes. The duration of longest well period and quality-of-life measuresmay also be promising efficacy measures. Each of these represents in itself acomposite outcome assessment, which avoids the problem of misinterpretationof improvement on a mania or depression scale as improvement when it actuallyrepresents affective switch. Whenever mood-rating scales are used, concurrentmeasurement should be made for both depression and mood elevation.ConclusionThe complexity of bipolar disorder and its subtypes need not discourage clinicaltrials. Simple investigational strategies can facilitate the conduct of clinical trialsfor mixed episodes and rapid cycling. Recommendations for studies of treatmentfor mixed episodes include constructing a trial design for mixed episode subjectonly, requiring the presence of mixed features for at least 4 weeks prior torandomization, and use of composite outcome measures. For rapid cycling, thedevelopment of standard operating procedures and definitions for prospectiveassessment can reduce the complex problem of phase counting to a reliablecategorical determination (0, 1, >1). Recommendations offered include randomizingsubjects on the basis of prospectively assessed active cycling and determiningresponse to treatment over periods of at least 6 months.DefinitionsCurrent rapid cycling1. Patient meets the criteria for bipolar disorder and has had four episodes ormore in the preceding 12 months2. Patient has experienced four episodes or two complete cycles within the preceding12 months. Longest remission over the past 6 months does not exceed 12 weeksHistory of rapid cycling1. Patient meets criteria for bipolar disorder2. Patient has had at least four episodes or two complete cycles in any 12-monthperiodSecondary rapid cycling1. Patient meets criteria for bipolar disorder