RT Journal
A1 Geller B, Luby JL, Joshi P, et al
T1 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
JF Archives of General Psychiatry
JO Archives of General Psychiatry
YR 2012
FD May 1
VO 69
IS 5
SP 515
OP 528
DO 10.1001/archgenpsychiatry.2011.1508
UL http://dx.doi.org/10.1001/archgenpsychiatry.2011.1508
AB 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%; χ21 = 16.9, P &lt; .001) and vs divalproex sodium (68.5% vs 24.0%; χ21 = 28.3, P &lt; .001). Response to lithium vs divalproex sodium did not differ. The discontinuation rate was higher for lithium than for risperidone (χ21 = 6.4, P = .011). Increased weight gain, body mass index, and prolactin level occurred with risperidone vs lithium (F1,212 = 45.5, P &lt; .001; F1,212 = 39.1, P &lt; .001; and F1,213 = 191.4, P &lt; .001, respectively) and vs divalproex sodium (F1,212 = 34.7, P &lt; .001; F1,212 = 45.3, P &lt; .001; and F1,213 = 209.4, P &lt; .001, respectively). The thyrotropin level increased in subjects taking lithium (t62 = 11.3, P &lt; .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