Effect of Divalproex on Metabolic Parameters Is Dose Related in Migraine Prophylaxis

Abstract

To examine the metabolic effects of three divalproex dosing regimens in patients with migraine. Epidemiological and clinical studies have demonstrated a strong association between serum lipid levels and the development of coronary artery disease. Thus, it is important to understand the impact of chronically administered medications on serum lipids. Metabolic properties of divalproex, an approved and commonly used treatment for migraine prophylaxis, have not been systematically studied in patients with migraine. Adult patients with migraine were randomized to receive one of three daily doses of divalproex (500 mg [n = 45], 1000 mg [n = 43], or 1500 mg [n = 44]) or placebo (n = 44) for 12 weeks. Post hoc analyses were performed to determine the effects of divalproex on total cholesterol, glucose, weight, and body mass index (BMI). The treatment groups were similar at baseline based on demographic and clinical characteristics and the use of concomitant medications. Divalproex resulted in a dose-related mean decrease from baseline in total cholesterol: -5.7 mg/dL or 3% reduction with 500 mg/day; -8.4 mg/dL or 4% reduction with 1000 mg/day; and -12.8 mg/dL or 7% reduction with 1500 mg/day (P < .05 for 1500 mg/day vs. placebo). There were no differences between any divalproex dose group and placebo for mean change from baseline in glucose, weight, or BMI. Divalproex results in a dose-dependent reduction in serum cholesterol within the first 3 months of therapy, with no significant change in serum glucose or BMI.