Migraine Prophylaxis With Divalproex

Objective: To compare the effectiveness and safety of divalproex sodium (Depakote) and placebo in the prophylaxis of migraine headache. Design: Multicenter, double-blind, randomized, placebo-controlled investigation, having a 4-week, single-blind placebo baseline phase and a 12-week treatment phase (4-week dose adjustment, 8-week maintenance). Setting: Eight headache/neurology clinics throughout the United States. Patients: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. Intervention: Divalproex and placebo dosages titrated in blinded fashion during dose adjustment period to achieve actual/sham trough valproate sodium concentrations of approximately 70 to 120 mg/L. Measurements and Main Results: During the treatment phase, the mean migraine headache frequency per 4 weeks was 3.5 in the divalproex group and 5.7 in the placebo group ( P ≤.001), compared with 6.0 and 6.4, respectively, during the baseline phase. Forty-eight percent of divalproex-treated patients and 14% of placebo-treated patients showed a 50% or greater reduction in migraine headache frequency from the baseline phase ( P P , not significant). Conclusions: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.