title: Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment.
abstract: OBJECTIVE
  The Treatment of Early Age Mania (TEAM) study evaluated lithium, risperidone, and divalproex sodium (divalproex) in children with bipolar I disorder who were naive to antimanic medication, or were partial or nonresponders to 1 of 3 study medications. This report evaluates the benefit of either an add-on or a switch of antimanic medications for an 8-week trial period in partial responders and nonresponders, respectively.
  
  
  METHODS
  TEAM is a randomized, controlled trial of individuals (N = 379) aged 6 to 15 years (mean ± SD = 10.2 ± 2.7 years) with DSM-IV bipolar I disorder (mixed or manic phase). Participants (n = 154) in this report were either nonresponders or partial responders to 1 of the 3 study medications. Nonresponders (n = 89) were randomly assigned to 1 of the other 2 antimanic medications and cross-tapered. Partial responders (n = 65) were randomly assigned to 1 of 2 other antimanic medications as an add-on to their initial medication. Adverse event (AE) rates are reported only for the add-on group.
  
  
  RESULTS
  Response rate for children switched to risperidone (47.6%) was higher than for those switched to either lithium (12.8%; p = .005; number needed to treat [NNT] = 3; 95% CI = 1.71-9.09) or divalproex (17.2%; p = .03; NNT = 3; 95% CI = 1.79-20.10); response rate for partial responders who added risperidone (53.3%) was higher than for those who added divalproex (0%; p = .0002; NNT = 2; 95% CI = 1.27-3.56) and trended higher for lithium (26.7%; p = .07; NNT = 4). Reported AEs in the add-on group were largely consistent with the known AE profile for the second medication. Weight gain (kg) was observed for all add-on medications: lithium add-on (n = 29 of 30) = 1.66 ± 1.97; risperidone add-on (n = 15 of 15) = 2.8 ± 1.34; divalproex add-on (n = 19 of 20) = 1.42 ± 1.96. There was no evidence at the 5% significance level that the average weight gain was different by study medication for partial responders (p = .07, 1-way analysis of variance).
  
  
  CONCLUSIONS
  Risperidone appears to be more useful than lithium or divalproex for children with bipolar I disorder and other comorbid conditions who are nonresponders or partial responders to an initial antimanic medication trial. 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: Weill Cornell Medical College, New York Presbyterian Hospital, New York. Electronic address: jtw9001@med.cornell.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Walkup
authors.affiliation: University of Texas Medical Branch, Galveston.
authors.forename: Karen Dineen
authors.initials: KD
authors.lastname: Wagner
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Leslie
authors.initials: L
authors.lastname: Miller
authors.affiliation: Johns Hopkins Bloomberg School of Public Health.
authors.forename: Gayane
authors.initials: G
authors.lastname: Yenokyan
authors.affiliation: Washington University in St. Louis.
authors.forename: Joan L
authors.initials: JL
authors.lastname: Luby
authors.affiliation: Children's National Medical Center, George Washington University School of Medicine, Washington, DC.
authors.forename: Paramjit T
authors.initials: PT
authors.lastname: Joshi
authors.affiliation: Nationwide Children's Hospital and The Ohio State University/Wexner Medical Center, Columbus.
authors.forename: David A
authors.initials: DA
authors.lastname: Axelson
authors.affiliation: Children's National Medical Center, George Washington University School of Medicine, Washington, DC.
authors.forename: Adelaide
authors.initials: A
authors.lastname: Robb
authors.affiliation: Children's National Medical Center, George Washington University School of Medicine, Washington, DC.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Salpekar
authors.affiliation: University of Texas Medical Branch, Galveston.
authors.forename: Dwight
authors.initials: D
authors.lastname: Wolf
authors.affiliation: Johns Hopkins Bloomberg School of Public Health.
authors.forename: Abanti
authors.initials: A
authors.lastname: Sanyal
authors.affiliation: University of Pittsburgh Medical Center/Western Psychiatric Institute and Clinic, Pittsburgh.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: National Institute of Mental Health (NIMH), Bethesda, MD.
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Riddle
mesh_terms: D000293:Adolescent; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D055118:Medication Adherence; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D016651:Lithium Carbonate; D014635:Valproic Acid; D018967:Risperidone
keywords: bipolar; mania; nonresponders; pharmacology; treatment