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

• Published in: Bipolar disorders Vol. 12; no. 6; pp. 593 - 605
• Main Authors: Pavuluri, Mani N, Henry, David B, Findling, Robert L, Parnes, Stephanie, Carbray, Julie A, Mohammed, Tahseen, Janicak, Philip G, Sweeney, John A
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2010
• Subjects: Adolescence; Adolescent; Affective disorders; Age; Antimanic Agents - adverse effects; Antimanic Agents - therapeutic use; Antipsychotic Agents - adverse effects; Antipsychotic Agents - therapeutic use; Bipolar disorder; Bipolar Disorder - drug therapy; Child; Children; Clinical trials; Depression; divalproex; double blind; Double-Blind Method; Drugs; Female; Humans; Male; Manganese; mania; Outpatients; Pediatrics; randomized; Regression analysis; Remission; Risperidone; Risperidone - adverse effects; Risperidone - therapeutic use; Treatment Outcome; Valproic acid; Valproic Acid - adverse effects; Valproic Acid - therapeutic use
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1111/j.1399-5618.2010.00850.x

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.