TY - JOUR
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
AU - Geller, Barbara
AU - Luby, Joan L.
AU - Joshi, Paramjit
AU - Wagner, Karen Dineen
AU - Emslie, Graham
AU - Walkup, John T.
AU - Axelson, David A.
AU - Bolhofner, Kristine
AU - Robb, Adelaide
AU - Wolf, Dwight V.
AU - Riddle, Mark A.
AU - Birmaher, Boris
AU - Nusrat, Nasima
AU - Ryan, Neal D.
AU - Vitiello, Benedetto
AU - Tillman, Rebecca
AU - Lavori, Philip
PY - 2012/5
Y1 - 2012/5
N2 - 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.
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-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.
UR - http://www.scopus.com/inward/record.url?scp=84860742323&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860742323&partnerID=8YFLogxK
U2 - 10.1001/archgenpsychiatry.2011.1508
DO - 10.1001/archgenpsychiatry.2011.1508
M3 - Article
C2 - 22213771
AN - SCOPUS:84860742323
SN - 0003-990X
VL - 69
SP - 515
EP - 528
JO - Archives of General Psychiatry
JF - Archives of General Psychiatry
IS - 5
ER -