NEW YORK (Reuters Health) – In children with attention deficit hyperactivity disorder (ADHD), adding divalproex to stimulant therapy can improve refractory aggression, a small study suggests.

“Stimulant medications for ADHD demonstrate strong efficacy for its core symptoms and often ameliorate comorbid disruptive disorders,” lead author Dr. Joseph C. Blader, from Stony Brook University School of Medicine, New York, and colleagues note. “However, a substantial proportion of children with ADHD do not experience satisfactory reductions in aggressive behavior with stimulant treatment.”

Recent research has shown that monotherapy with divalproex, an antimanic/anticonvulsant agent, can reduce aggression in children and adolescents with a variety of psychiatric disorders. The drug’s benefit as adjunctive therapy for stimulant-refractory ADHD-related aggression, however, was unclear, according to the researchers.

In the American Journal of Psychiatry for December, they report on 30 ADHD patients, 6 to 13 years of age, with stimulant-refractory aggression who were randomized to add placebo or divalproex to their treatment regimen for 8 weeks. Divalproex was given once daily; after titration, the daily dose was roughly 20 mg/kg. Families in both groups received weekly behavioral therapy.

One patient in the divalproex group and one in the placebo group withdrew from the study before first assessment. An additional patient in the placebo group was lost to follow-up before the first assessment.

Eight of 14 (57%) patients in the divalproex group versus just 2 of 13 (15%) in the placebo group had remission of their aggressive behavior, the authors state.

Divalproex was generally well tolerated, although children given the drug showed a trend toward treatment-emergent sadness and trouble falling asleep. Valproic acid levels were not correlated with side effects.

“This study points the way to a more complicated, but ultimately more realistic, polypharmacology in developmental psychiatry that should produce better results for our patients, rather than some of the unfortunate ‘polypsychopharmacology’, where a high number of agents is combined in suboptimal doses,” Dr. Hans Steiner and Dr. Niranjan S. Karnik, from Stanford University, California, write in a related editorial.

Reference:
Am J Psychiatry 2009;166:1315-1317,1392-1401.