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Safety of Divalproex Sodium in Migraine Prophylaxis: An Open-Label, Long-term Study


  • A complete list of the participants in this research study appears at the end of this article.

Address all correspondence to Dr. Stephen D. Silberstein, Jefferson Headache Center, Thomas Jefferson University, 111 South 11th Street, Suite 81309, Philadelphia, PA 19107.


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.