Treatment of Early-Age Mania: Outcomes for Partial and Nonresponders to Initial Treatment

John T. Walkup*, Karen Dineen Wagner, Leslie Miller, Gayane Yenokyan, Joan L. Luby, Paramjit T. Joshi, David A. Axelson, Adelaide Robb, Jay A. Salpekar, Dwight Wolf, Abanti Sanyal, Boris Birmaher, Benedetto Vitiello, Mark A. Riddle

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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. Method 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). Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1008-1019
Number of pages12
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number12
StatePublished - 2015


  • bipolar
  • mania
  • nonresponders
  • pharmacology
  • treatment

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Developmental and Educational Psychology


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