Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group.

CONTEXT: The adverse event profile of long-term divalproex therapy for epilepsy is well established, but little is known about the tolerability or safety of divalproex in long-term migraine prophylaxis. OBJECTIVE: Evaluate the long-term safety and efficacy of divalproex sodium in migraine prophylaxis. DESIGN: Open-label, long-term study, of up to 3 years, of patients who completed one of two multicenter, double-blind, randomized, placebo-controlled studies. SETTING: Eighteen headache/neurology centers throughout the United States. PATIENTS: One hundred sixty-three patients: 46 treated with placebo, 117 treated with divalproex for migraine in previous studies. INTERVENTION: Divalproex therapy initiated at 500 mg/day (250 mg twice daily), with adjustment in dose and dosing frequency possible after 1 to 3 days. MAIN OUTCOME MEASURES: Number and proportion of patients reporting treatment-emergent adverse events, prevalence and incidence for each treatment-emergent adverse event, vital signs, body weight, 4-week migraine rates and proportion of patients with 50% or greater reduction in rate over time. RESULTS: Treatment lasted more than 180 days for 71% of patients and more than 360 days for 48% of patients. Improvements in the 4-week, change-from-baseline migraine rates were seen during each of the 3- and 6-month time intervals. CONCLUSIONS: Divalproex is effective for migraine prophylaxis, and initial benefits are maintained for periods in excess of 1080 days.