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

82 O. Elhaj and J. R. CalabreseTable 3.3 Responder analyses on completers after 6 months of combined lithium anddivalproex in bipolar rapid cyclingWithoutADA (n ¼ 109)WithADA (n ¼ 28)Mood stabilization 50 37Time required (months) 4.7 5.4Marked antimanic effect 88 77Cycling into depression (n) 42 16Marked antidepressant effect 61 59Cycling into hypomania/mania/mixed states (n) 13 9Values are percentages unless otherwise specified.ADA, Alcohol and drug abuse.phase of an ongoing and still blinded 6-month maintenance study designed tocompare the efficacy of lithium monotherapy with the combination of lithium anddivalproex after 6 months of open stabilization with the combination. Inclusioncriteria included presence of rapid cycling and an episode of hypomania or maniawithin the 3 months preceding study entry, and meeting DSM-IV criteria foreither abuse of, or dependence on, alcohol, cannabis, and/or cocaine. All patientswere required to attend a 12-step-based intensive outpatient chemical dependencetreatment program. Patients enrolled were mostly men with BP-I disorder presentingin the depressed phase. However, manias and mixed states were morecommonly observed at study entry as compared with the cohort of non-comorbidpatients with rapid cycling. The median number of affective episodes meetingDSM-IV criteria in the 12 months prior to study entry was eight. Of the 28 subjectswho were not randomly assigned because they were non-responsive to combinedtreatment, 64% were experiencing refractory depression and 36% were experiencingrefractory hypomania/mania/mixed states. Twenty-five percent of patientsmet criteria for an early remission to their alcohol or drug-abuse disorder at theend of open stabilization. The responder analyses indicated that, of 39 completers,only 37% met criteria for a marked bimodal response and were randomly assignedto the maintenance phase of the study; 59% of patients met criteria for a markedantidepressant response, and 77% met criteria for a marked antimanic response(Tables 3.2 and 3.3).The final results of these two studies will shed long-awaited light on the efficacyof the, apparently needed, combined pharmacotherapy for this challenging subtypeof bipolar disorder, especially with its high comorbidity rate with alcohol- andsubstance-related disorders.