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

374 G. Sachs and M. Graveshas become recognized as an important area of unmet clinical need. The DSM-IVclassifies rapid cycling as a course specifier rather than a subtype of bipolardisorder. Although rapid cycling is associated with relatively poor response totreatment and persistence of higher rates of cycling than non-rapid cycling (Baueret al., 1994; Baldessarini et al., 2000), bipolar illness, indices such as family history,and age of onset do not separate rapid-cycling from non-rapid-cycling patients(Bauer et al., 1994). Furthermore, prospective follow-up reveals rapid cycling isseldom persistent. Among subjects diagnosed as rapid cycling on entry into theNIMH Collaborative Depression study, Coryell et al. (1992) found only a thirddemonstrated four or more episodes through the first year of prospective followupand in only 3% did rapid cycling persist through 3 years.The DSM-IV concept of rapid cycling retains Dunner and colleagues’ definitionof rapid cycling as four or more episodes in 1 year (Dunner et al., 1977).Importantly, the DSM-IV concept of rapid cycling requires counting episodes;either as four episodes separated by periods of remission or a switch from anepisode of one polarity to an episode of opposite polarity. Strict application of theDSM definitions can provide upper as well as lower boundaries for annual episodefrequency consistent with the rapid-cycling concept. Notably, the DSM requiresseparate episodes be bounded by a period of full or partial remission lasting at least8 weeks and the definition of mania requires the presence of symptoms for at least1 week. Therefore, in the course of a year, patients following this 9-week patterncould have no more than six episodes. A pattern of continuous cycling in whicha patient abruptly switches from a 1-week period meeting criteria for mania to a2-week period of symptoms meeting criteria for depression could produce a highercycle frequency. Even repetition of this 3-week pattern throughout a year couldproduce an annual cycle frequency only as high as 17 per year. Many patients andpractitioners, however, report cycle frequencies greatly exceeding 17 per year. Infact, it has become common to hear descriptions of patients with multiple cycleswithin a single day. These various forms of so-called ‘ultrarapid cycling’ arecharacterized by ‘‘truncated episodes’’ (Bauer et al., 1994). The concept of truncatedepisodes allows a phase to count toward the diagnosis of rapid cycling evenwhen that phase is too short to qualify as a DSM-defined episode. The advantage ofthe truncated episode concept is obvious: it allows the rapid-cycling designation tobe applied to patients such as those described with 48-h periods of depressionalternating with 48-h periods of mood elevation. The problem, however, is thatwhen we suspend the requirement to meet the definition for an episode we lackcriteria to distinguish meaningfully mixed episodes from rapid cycling or evenreliably distinguish a phase of illness from an emotion. Using the concept oftruncated episodes in clinical trials, therefore, requires researchers to use greatcaution and standardized counting procedures.