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

69 Rapid-cycling bipolar disorderincreased prevalence of alcohol and drug abuse comorbidity compared to nonrapidcyclers has not been explored. Whether patients with bipolar disorder andcomorbid alcohol or drug abuse/dependence have an increased prevalence of rapidcycling has likewise not been explored. However, preliminary data suggest thatbipolar patients with comorbid alcohol and/or drug abuse/dependence cyclefrequently, consistently experiencing twice as many lifetime hospitalizations(Keller et al., 1986; Brady et al., 1991; Sonne et al., 1994; Haywood et al., 1995).Other manifestations of comorbidity in rapid cyclers have not yet been systematicallystudied. However, anecdotal reports have associated the onset of rapidcycling with neurologic events or states such as strokes (Berthier, 1992), subarachnoidhemorrhages (Blackwell, 1991), and profound mental retardation withperiodic aggressive acting-out behavior (Glue, 1989; Lowry and Sovner, 1992).After the publication of the above-mentioned book, Calabrese et al. (2001)reported that comorbidity with alcohol, cannabis, and/or cocaine abuse or dependenceappeared to alter prognosis by increasing the prevalence of poor compliance,not by directly affecting the spectrum of activity of combined treatment withlithium and divalproex. In that study, Calabrese et al. evaluated the spectrum ofefficacy of combined treatment with lithium and divalproex in a cohort of 84patients with rapid-cycling BP-I or BP-II disorder comorbid with a current historyof either abuse of or dependence on alcohol, cannabis, and/or cocaine. At the timeof study entry, 86% of patients were using alcohol, 45% cannabis, and 40%cocaine. Of those using alcohol, 71% met DSM-IV criteria for dependence and29% for abuse. Of those using cannabis, 24% met criteria for dependence, and76% for abuse. Of those using cocaine, 65% met criteria for dependence and 35%for abuse. The profile of lifetime abuse/dependence was alcohol/cannabis/cocaine(42%), alcohol and cannabis (22%), alcohol alone (20%), alcohol and cocaine(12%), cannabis and cocaine (1%), cannabis alone (1%), and cocaine alone (1%).Physiologic dependence was present in 65% of those using alcohol, 8% of thoseusing cannabis, and 57% of those using cocaine. These data suggest that themajority of alcohol and cocaine use, but not cannabis use, in rapid-cycling bipolardisorder is accompanied by physiologic dependence. A more detailed discussion oftheir outcome results will follow later in the chapter. Additionally, substance abusehas been linked to increasing the already high risk of suicide in rapid-cyclingbipolar disorder (Nierenberg et al., 2001; Sachs et al., 2001).PharmacotherapyTreatment recommendationsWhile the newly revised practice guidelines for the treatment of patients withbipolar disorder, published by the American Psychiatric Association in 2002,