A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents

Barbara Geller*, Joan L. Luby, Paramjit Joshi, Karen Dineen Wagner, Graham Emslie, John T. Walkup, David A. Axelson, Kristine Bolhofner, Adelaide Robb, Dwight V. Wolf, Mark A. Riddle, Boris Birmaher, Nasima Nusrat, Neal D. Ryan, Benedetto Vitiello, Rebecca Tillman, Philip Lavori

*Corresponding author for this work

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

Context: There was a paucity of comparative pharmacological research for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Objective: To investigate which medication to administer first to antimanic medication-naive subjects. Design, Setting, and Participants: The Treatment of Early Age Mania (TEAM) study recruited 6-to 15-year-old children and adolescents with DSM-IV bipolar I disorder (manic or mixed phase) at 5 US sites from 2003 to 2008 into a controlled, randomized, no-patientchoice, 8-week protocol. Blinded, independent evaluators conducted all baseline and end-point assessments. Interventions: Subjects received a titrated schedule of lithium, divalproex sodium, or risperidone. Medications were increased weekly only if there was inadequate response, and no dose-limiting adverse effects, to maximum doses of lithium carbonate (1.1-1.3 mEq/L), divalproex sodium (111-125 μg/mL), and risperidone (4-6 mg). Main Outcome Measures: Primary outcome measures were the Clinical Global Impressions for Bipolar Illness Improvement-Mania and the Modified Side Effects Form for Children and Adolescents. Results: There were 279 antimanic medication-naive subjects (mean [SD] age, 10.1 [2.8] years; 50.2% female) who had the following characteristics:100% elated mood and/or grandiosity, 77.1% psychosis, 97.5% mixed mania, 99.3% daily rapid cycling, and mean (SD) mania duration of 4.9 (2.5) years. The mean (SD) titrated lithium level was 1.09 (0.34) mEq/L, and the mean (SD) divalproex sodium level was 113.6 (23.0) μg/mL. The mean (SD) titrated risperidone dose was 2.57 (1.21) mg. Higher response rates occurred with risperidone vs lithium (68.5% vs 35.6%; X 1 2 1=16.9, P<.001) and vs divalproex sodium (68.5% vs 24.0%; X 1 2 1=28.3, P<.001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (X 1 2 1=6.4, P=.011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F 1,212=45. 5, P<.001; F 1,212=39.1, P<.001; and F 1,213=191.4, P<.001, respectively) and vs divalproex sodium (F 1,212=34.7, P<.001; F 1,212=45.3, P<.001; and F 1,213=209.4, P<.001, respectively). The thyrotropin level increased in subjects taking lithium (t 62=11.3, P<.001). Conclusions: Risperidone was more efficacious than lithium or divalproex sodium for the initial treatment of childhood mania but had potentially serious metabolic effects. Trial Registration: clinicaltrials.gov Identifier: NCT00057681.

Original languageEnglish (US)
Pages (from-to)515-528
Number of pages14
JournalArchives of general psychiatry
Volume69
Issue number5
DOIs
StatePublished - May 1 2012

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

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    Geller, B., Luby, J. L., Joshi, P., Wagner, K. D., Emslie, G., Walkup, J. T., Axelson, D. A., Bolhofner, K., Robb, A., Wolf, D. V., Riddle, M. A., Birmaher, B., Nusrat, N., Ryan, N. D., Vitiello, B., Tillman, R., & Lavori, P. (2012). A randomized controlled trial of risperidone, lithium, or divalproex sodium for initial treatment of bipolar I disorder, manic or mixed phase, in children and adolescents. Archives of general psychiatry, 69(5), 515-528. https://doi.org/10.1001/archgenpsychiatry.2011.1508