title: Placebo-controlled trial of valproic Acid versus risperidone in children 3-7 years of age with bipolar I disorder.
abstract: OBJECTIVE
  The objective of this study was to determine the efficacy and safety of valproic acid versus risperidone in children, 3-7 years of age, with bipolar I disorder (BPD), during a mixed or manic episode.
  
  
  METHODS
  Forty-six children with Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Revision (DSM-IV-TR) diagnosis of bipolar disorder, manic, hypomanic, or mixed episode, were recruited over a 6 year period from two academic outpatient programs for a double-blinded, placebo-controlled trial in which subjects were randomized in a 2:2:1 ratio to risperidone solution, valproic acid, or placebo.
  
  
  RESULTS
  After 6 weeks of treatment, the least-mean Young Mania Rating Scale (YMRS) total scores change, adjusted for baseline YMRS scores, from baseline by treatment group was: Valproic acid 10.0±2.46 (p=0.50); risperidone 18.82±1.55 (p=0.008); and placebo 4.29±3.56 (F=3.93, p=0.02). The mixed models for repeated measure (MMRM) analysis found a significant difference for risperidone-treated subjects versus placebo treated subjects (p=0.008) but not for valproic acid-treated subjects versus placebo-treated subjects (p=0.50). Treatment with risperidone over 6 weeks led to increased prolactin levels, liver functions, metabolic measures, and weight/body mass index (BMI). Treatment with valproic acid led to increases in weight/BMI and decreases in total red blood cells (RBC), hemoglobin, and hematocrit.
  
  
  CONCLUSIONS
  In this small sample of preschool children with BPD, risperidone demonstrated clear efficacy versus placebo, whereas valproic acid did not. The laboratory and weight findings suggest that younger children with BPD are more sensitive to the effects of both of these psychotropics, and that, therefore, frequent laboratory and weight monitoring are warranted.
authors.affiliation: 1 The Ohio State University Wexner Medical Center/Nationwide Children's Hospital , Columbus, Ohio.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kowatch
authors.forename: Russell E
authors.initials: RE
authors.lastname: Scheffer
authors.forename: Erin
authors.initials: E
authors.lastname: Monroe
authors.forename: Sergio
authors.initials: S
authors.lastname: Delgado
authors.forename: Mekibib
authors.initials: M
authors.lastname: Altaye
authors.forename: Denise
authors.initials: D
authors.lastname: Lagory
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use*; D014635:Valproic Acid / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D014635:Valproic Acid; D018967:Risperidone