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

381 Investigational strategiesTable 17.2 Causes of rapid cycling* Brain injury– Mental retardation– Head trauma– Multiple sclerosis* Neuroendocrine– Hypothyroidism– Reproductive hormones* Psychotropic drugs– Alcohol– Stimulants– Antidepressant drugs* Circadian rhythm abnormalityretrospective measures like the LIFE can make more meaningful assessmentswhen applied over short intervals. Standard operating procedures for assigning aclinical status for each week using the CMF appear to offer a reasonably reliablemeans of prospective assessment. Outpatient studies could employ either ofthese techniques to establish episode pattern as well as measure phase changes.Treatment efficacy outcome criteria specifically for rapid cycling are not wellestablished. Calabrese et al. (2000) reported results for several efficacy measuresused on the double-blind trial comparing the outcome for rapid-cycling patientsmaintained on placebo or lamotrigine. Interestingly, time to intervention for anew mood episode proved relatively insensitive, but percentage remaining stablewithout relapse through the 6-month follow-up period, time to drop-out, changefrom baseline severity, and change from baseline Global Assessment Scale scorewere useful in distinguishing between lamotrigine and placebo.The most compelling of these measures, percentage remaining stable withoutrelapse, becomes highly relevant to course of illness, in large part because thefollow-up was carried out for 6 months. Beyond the sense of clinical relevance, it isnoteworthy that survival curves for both active and placebo-treated subjects inmost maintenance studies nearly always begin with an initial period of sharpdecline lasting 6–18 weeks. Therefore, study designs with follow-up of durationshorter than 6 months are statistically disadvantageous.Outcome criteria, such as percentage minimally symptomatic (meeting CMFcriteria for recovered or recovering), correspond to ‘‘stable without relapse,’’ butmay be insensitive to the beneficial effects of treatments that reduce the frequencybut do not eliminate cycling.