• Online Features  This Article  • Full text  • PDF  • eSupplement  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Pediatrics  • Adolescent Medicine  • Psychiatry  • Adolescent Psychiatry  • Bipolar Disorder  • Child Psychiatry  • Psychopharmacology  • Quality of Care  • Patient Safety/ Medical Error  • Randomized Controlled Trial  • Drug Therapy  • Adverse Effects  • Alert me on articles by topic  Social Bookmarking   What's this?

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

Arch Gen Psychiatry. Published online January 2, 2012. doi:10.1001/archgenpsychiatry.2011.1508

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-patient-choice, 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%; ²₁ = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; ²₁ = 28.3, P < .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (²₁ = 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 (t₆₂ = 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

Author Affiliations: Department of Psychiatry, Washington University in St Louis, Missouri (Drs Geller and Luby and Mss Bolhofner and Tillman); Department of Psychiatry and Behavioral Sciences, Children's National Medical Center, Washington, DC (Drs Joshi, Robb, and Nusrat); Department of Psychiatry, University of Texas Medical Branch, Galveston (Drs Wagner and Wolf), and Department of Psychiatry, University of Texas Southwestern, Dallas (Dr Emslie); Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland (Drs Walkup and Riddle); National Institute of Mental Health, Bethesda, Maryland (Dr Vitiello); Department of Psychiatry, University of Pittsburgh, Pennsylvania (Drs Axelson, Birmaher, and Ryan); and Department of Health Research and Policy, Stanford University, California (Dr Lavori). Dr Walkup is now with the Department of Psychiatry, Weill Cornell Medical College, New York, New York.

CiteULike    Connotea    Delicious    Digg    Facebook    Reddit    Technorati    Twitter     What's this?