Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study

Abstract

To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder. The Treatment of Early Age Mania (TEAM) studyis a multicenter, prospective, randomized, masked comparison of divalproex sodium (VAL), lithium carbonate (LI), and risperidone (RISP) in an 8-week parallel clinical trial. A total of 279 children and adolescents with DSM-IV diagnoses of bipolar I disorder, mixed or manic, aged 6 to 15years were enrolled. The primary outcome measure was improvement on the Clinical Global Impression scale for depression (CGI-BP-I-D). Secondary outcome measures included the Children's Depression Rating Scale (CDRS-R) and suicidality status. Statistics included longitudinal analysis of outcomes using generalized linear mixed models with random intercept both for the complete data set and by using last observation carried forward. CGI-BP-I-D ratings were better in the RISP group (60.7%) as compared to the LI (42.2%; p= .03) or VAL (35.0%; p= .003) groups from baseline to the end of the study. CDRS scores in all treatment groups improved equally by study end. In week 1, scores were lower with RISP compared to VAL (mean= 4.72, 95% CI= 2.67, 6.78), and compared to LI (mean= 3.63, 95% CI= 1.51, 5.74), although group differences were not present by the end of the study. Suicidality was infrequent, and there was no overall effect of treatment on suicidality ratings. Depressive symptoms, present in the acutely manic or mixed phase of pediatric bipolar disorder, improved with all 3 medications, though RISP appeared to yield more rapid improvement than LI or VAL and was superior using a global categorical outcome. Clinical trial registration information-Study of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents (TEAM); http://clinicaltrials.gov; NCT00057681.