The effectiveness and safety of divalproex sodium administered daily in migraine prophylaxis were evaluated in 23 children, ages 7 to 17 years (mean, 12.4 yrs), at Ohio State University College of Medicine, Children’s Hospital, Columbus, OH. Dosage ranged from 250-1125 mg/day (3.1 to 32.9 mg/kg/day). Valproate serum levels varied from 18 to 82.3 mcg/ml. Comorbid psychiatric disorders occurred in 7 patients (2 with bipolar disorder, 1 with depression, 2 with ADHD, 1 with ADD, and 1 with ODD). Six patients had epilepsy, and seizures were well controlled by divalproex. A greater than 50% reduction in migraine attacks was obtained in 15 (65%) patients, and 6 of these were headache free. A significant response occurred in patients with migraine alone or comorbid epilepsy. In those with comorbid psychiatric and behavior disorders headaches were not improved. Patients with comorbid epilepsy tended to require higher doses of divalproex (13 mg/kg/day) than those with psychiatric disorders (11 mg/kg/day) or those with migraine alone (8.5 mg/kg/day). The average daily dose for children who responded (11.6 mg/kg/day) was not significantly different from that taken by nonresponders (11.9 mg/kg/day). Side effects requiring withdrawal of divalproex occurred in 4 patients and included weight gain, lethargy, anorexia, and alopecia. None had significant hematological or hepatic dysfunction requiring drug termination. [1]
COMMENT. Divalproex is effective in migraine prophylaxis in children with headache alone or with comorbid epilepsy. Migraine in children with comorbid behavioral disorders does nor respond to divalproex. Previous double-blind, placebo-controlled studies have confirmed the efficacy of divalproex sodium in treatment of migraine, as reviewed by Siberstein SD [2], but valproate is generally not recommended for migraine prevention in children under 10 years of age (see Progress in Pediatric Neurology III, PNB Publ, 1997;ppl90-191).