title: Depression and Suicidality Outcomes in the Treatment of Early Age Mania Study.
abstract: OBJECTIVE
  To assess the efficacy of mood-stabilizing medications for depression and suicidality in pediatric bipolar disorder.
  
  
  METHODS
  The Treatment of Early Age Mania (TEAM) study is 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 15 years 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Kennedy Krieger Institute and Johns Hopkins University School of Medicine, Baltimore. Electronic address: Salpekar@kennedykrieger.org.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Salpekar
authors.affiliation: Children's National Medical Center and George Washington University, Washington, DC; American Academy of Child and Adolescent Psychiatry (AACAP) and with the American Board of Psychiatry and Neurology (ABPN).
authors.forename: Paramjit T
authors.initials: PT
authors.lastname: Joshi
authors.affiliation: Nationwide Children's Hospital and The Ohio State University, Columbus.
authors.forename: David A
authors.initials: DA
authors.lastname: Axelson
authors.affiliation: Johns Hopkins University School of Medicine.
authors.forename: Shauna P
authors.initials: SP
authors.lastname: Reinblatt
authors.affiliation: Johns Hopkins Biostatistics Center at Johns Hopkins Bloomberg School of Public Health.
authors.forename: Gayane
authors.initials: G
authors.lastname: Yenokyan
authors.affiliation: Johns Hopkins Biostatistics Center at Johns Hopkins Bloomberg School of Public Health.
authors.forename: Abanti
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: New York Presbyterian Hospital-Weill Cornell Medical College, New York.
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.affiliation: National Institute of Mental Health (NIMH), Bethesda, MD.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: Washington University in St. Louis.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Luby
authors.affiliation: University of Texas Medical Branch at Galveston.
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Children's National Medical Center and George Washington University, Washington, DC.
authors.forename: Nasima
authors.initials: N
authors.lastname: Nusrat
authors.affiliation: Johns Hopkins University School of Medicine.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Riddle
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000175:diagnosis / Q000188:drug therapy*; D002648:Child; D003863:Depression / Q000175:diagnosis*; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D010349:Patient Compliance; D011446:Prospective Studies; D018967:Risperidone / Q000627:therapeutic use*; D013405:Suicide / Q000523:psychology*; D016896:Treatment Outcome; D014481:United States; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D016651:Lithium Carbonate; D014635:Valproic Acid; D018967:Risperidone
keywords: bipolar; clinical trial; depression; pediatrics; treatment