Adjunctive divalproex versus placebo for children with ADHD and aggression refractory to stimulant monotherapy.
OBJECTIVE
The purpose of the present study was to evaluate the efficacy of divalproex for reducing aggressive behavior among children 6 to 13 years old with attention deficit hyperactivity disorder (ADHD) and a disruptive disorder whose chronic aggression was underresponsive to a prospective psychostimulant trial.


METHODS
Children received open stimulant treatment during a lead-in phase that averaged 5 weeks. Agent and dose were assessed weekly and modified to optimize response. Children whose aggressive behavior persisted at the conclusion of the lead-in phase were randomly assigned to receive double-blind, flexibly dosed divalproex or a placebo adjunctive to stimulant for 8 weeks. Families received weekly behavioral therapy throughout the trial. The primary outcome measure was the proportion of children whose aggressive behavior remitted, defined by post-trial ratings of negligible or absent aggression.


RESULTS
A significantly higher proportion of children randomly assigned to divalproex met remission criteria (eight out of 14 [57%]) than those randomly assigned to placebo (two out of 13 [15%]). Divalproex was generally well tolerated.


CONCLUSIONS
Among children with ADHD whose chronic aggressive behavior is refractory to optimized stimulant treatment, the addition of divalproex increases the likelihood that aggression will remit. A larger trial is necessary to specify with greater precision the magnitude of benefit for adjuvant divalproex.
Blader
Joseph C
JC
Stony Brook University School of Medicine, Stony Brook, NY 11794-8790, USA. joseph.blader@stonybrook.edu
Schooler
Nina R
NR
Jensen
Peter S
PS
Pliszka
Steven R
SR
Kafantaris
Vivian
V
D000293:Adolescent; D000374:Aggression / Q000187:drug effects* / Q000523:psychology; D018692:Antimanic Agents / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy* / Q000453:epidemiology; D001521:Behavior Therapy / Q000379:methods; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D003131:Combined Modality Therapy; D015897:Comorbidity; D019955:Conduct Disorder / Q000188:drug therapy / Q000523:psychology; D003913:Dextroamphetamine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005196:Family Therapy / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use; D010919:Placebos; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use*
D018692:Antimanic Agents; D000697:Central Nervous System Stimulants; D010919:Placebos; D008774:Methylphenidate; D014635:Valproic Acid; D003913:Dextroamphetamine