Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder

Authors


  • Study drugs and matching placebo were provided by Johnson & Johnson and Abbott Pharmaceuticals. MNP’s work is currently supported by NIMH, NICHD, NARSAD, Dana Foundation, American Foundation for Suicide Prevention, and Marshall Reynolds Foundation; and she has received research support from GlaxoSmithKline in the past three years. RLF receives or has received research support, acted as a consultant, and/or served on the speakers bureau for Abbott, Addrenex, AstraZeneca, Biovail, Bristol-Myers Squibb, Forest, GlaxoSmithKline, Johnson & Johnson, KemPharm Lilly, Lundbeck, Neuropharm, Novartis, Organon, Otsuka, Pfizer, Sanofi-aventis, Sepracore, Shire, Solvay, Supernus Pharmaceuticals, Validus, and Wyeth. JAC is on the speakers bureau for AstraZeneca. PGJ has received research support from Bristol-Myers Squibb/Otsuka, Janssen, and Neuronetics, Inc.; has served in an advisory/consultant role for AstraZeneca, Bristol-Myers Squibb, and Neuronetics, Inc.; and is on the speakers bureau for AstraZeneca, Bristol-Myers Squibb, Janssen, Pfizer, and Neuronetics, Inc. JAS has received research support from NIH, Johnson & Johnson, GlaxoSmithKline, AstraZeneca, and Eli Lilly & Co. DBH, SP, and TM have no financial relationships to disclose.

Corresponding author:
Mani N. Pavuluri, MD, PhD
Department of Psychiatry
Institute for Juvenile Research
912 South Wood Street (M/C 913)
Chicago, IL 60612, USA
Fax: 312-413-0063
E-mail: mpavuluri@psych.uic.edu

Abstract

Pavuluri MN, Henry DB, Findling RL, Parnes S, Carbray JA, Mohammed T, Janicak PG, Sweeney JA. Double-blind randomized trial of risperidone versus divalproex in pediatric bipolar disorder. Bipolar Disord 2010: 12: 593–605. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S.

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.

Conclusion:  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.

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