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

72 O. Elhaj and J. R. CalabreseKaplan–Meier methodology was used to analyze survival data, and mediantimes to survival were calculated. Additionally, survival analyses were performedfor each bipolar subtype. The percentage of patients stable without relapse for6 months was analyzed using the Cochran–Mantel–Haenszel chi-squared test.Clinical efficacy scales (CGI-S, GAS) were evaluated using analysis of variance(ANOVA) at an ¼ 0.05 level of significance using both observed and lastobservation-carried-forward(LOCF) data.Treatment groups during the randomized phase (n ¼ 182) were similar withrespect to age, sex, race, medical history, psychiatric history, prior treatments,response to treatments, and current psychiatric state. The majority of patients wereclassified as having BP-I disorder (71%). A comparison of BP-I and BP-II patientsshowed no differences on key parameters. Compared with BP-II patients, BP-Ipatients had a greater prevalence of suicide attempts (40% versus 28%) andaverage number of lifetime hospitalizations (2.3 versus 0.7).Forty-nine placebo patients (56%) and 45 lamotrigine patients (50%) requiredadditional pharmacotherapy for emerging symptoms of a mood episode. Thedifference between the two general treatment groups in time to additional pharmacotherapydid not achieve statistical significance. The median survival timeswere 18 weeks for lamotrigine and 12 weeks for placebo. When survival in study(any premature discontinuation, including for additional pharmacotherapy) wasevaluated, the difference between the treatment groups was significant (P ¼ 0.04).For survival in study, the median survival times were 14 weeks for lamotrigine and8 weeks for placebo. Time to additional pharmacotherapy and survival in studydid not yield significant differences between lamotrigine and placebo in patientswith BP-I disorder. When time to additional pharmacotherapy was evaluated, atrend toward significance (P ¼ 0.07) was found in the separation between placeboand lamotrigine. Median survival time without additional pharmacotherapy forthe BP-II subtype was 17 weeks for lamotrigine and 7 weeks for placebo. Theoverall survival in study analysis yielded a significant separation between treatmentgroups (P ¼ 0.01). Median overall survival was 15 weeks for lamotrigine and4 weeks for placebo. The majority of those patients (80%) requiring additionalpharmacotherapy were treated for depressive symptoms; 20% were treated foremerging manic, hypomanic, or mixed symptoms.The percentage of patients who completed the 6-month randomized phaseclinically stable on monotherapy without evidence of relapse into hypomania,mania, or depression was significantly greater in the lamotrigine group than in theplacebo group. Of the 60 patients who were stable for 6 months of monotherapy,37 of 90 (41%) were in the lamotrigine group compared with 23 of 87 (26%) in theplacebo group (P ¼ 0.03). The difference for lamotrigine versus placebo was notstatistically significant for the BP-I subtype, but was significant (46% versus 18%,