Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder.
OBJECTIVE
To determine the relative effects of risperidone and divalproex in pediatric mania.


METHODS
This is a double-blind, randomized, outpatient clinical trial with 66 children and adolescents (mean age= 10.9 ± 3.3 years; age range= 8-18 years) with mania who were randomly assigned to either risperidone (0.5-2 mg/day, n= 33) or divalproex (60-120 μg/mL, n= 33) for a six-week period. Measures included the Young Mania Rating Scale (YMRS) and Child Depression Rating Scale-Revised (CDRS-R).


RESULTS
Mixed-effects regression models, with interaction between time and the active drug as predictors, found that the risperidone group had more rapid improvement than the divalproex group (p < 0.05), although final scores did not differ significantly between groups. Mixed models using only those subjects who completed the six-week study found similar results. The response rate on YMRS was 78.1% for risperidone and 45.5% for divalproex (p < 0.01). The remission rate for risperidone was 62.5%, compared with 33.3% for divalproex (p < 0.05). Improvement on the CDRS-R was significantly higher for the risperidone group relative to the divalproex group (p < 0.05). There were no significant differences between groups in safety, but subject retention was significantly higher at study endpoint in the risperidone group (p < 0.01). Dropout rate was 24% in the risperidone group and 48% in the divalproex group, with increased irritability being the most common reason for dropout in the latter. There was no significant weight gain in either group.


CONCLUSIONS
Results suggest that risperidone was associated with more rapid improvement and greater reduction in manic symptoms compared to divalproex. Although the results suggest that both drugs are safe, risperidone's lower attrition rate and lower rate of adverse events may suggest better toleration. Clinical trials with larger samples are required to confirm these preliminary findings.
Pavuluri
Mani N
MN
Department of Psychiatry, Institute for Juvenile Research, University of Illinois at Chicago, USA. mpavuluri@psych.uic.edu
Henry
David B
DB
Findling
Robert L
RL
Parnes
Stephanie
S
Carbray
Julie A
JA
Mohammed
Tahseen
T
Janicak
Philip G
PG
Sweeney
John A
JA
D000293:Adolescent; D018692:Antimanic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D010045:Outpatients; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid; D018967:Risperidone