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.
BACKGROUND
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.


METHODS
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.


METHODS
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).


METHODS
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%; χ(2)(1) = 16.9, P < .001) and vs divalproex sodium (68.5% vs 24.0%; χ(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 (χ(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.


BACKGROUND
clinicaltrials.gov Identifier: NCT00057681
Department of Psychiatry, Washington University in St Louis, 660 S Euclid, St Louis, MO 63110, USA. gellerb@wustl.edu
Barbara
B
Geller
Joan L
JL
Luby
Paramjit
P
Joshi
Karen Dineen
KD
Wagner
Graham
G
Emslie
John T
JT
Walkup
David A
DA
Axelson
Kristine
K
Bolhofner
Adelaide
A
Robb
Dwight V
DV
Wolf
Mark A
MA
Riddle
Boris
B
Birmaher
Nasima
N
Nusrat
Neal D
ND
Ryan
Benedetto
B
Vitiello
Rebecca
R
Tillman
Philip
P
Lavori
D000293:Adolescent; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D005260:Female; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D018692:Antimanic Agents; D016651:Lithium Carbonate; D014635:Valproic Acid; D018967:Risperidone