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 < or = .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 < .001). Among those with migraine headaches, divalproex-treated patients reported significantly less functional restriction than placebo-treated patients and used significantly less symptomatic medication per episode. No significant treatment group differences were observed in average peak severity or duration of individual migraine headaches. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significant).
Conclusions: Divalproex is an effective prophylactic drug for patients with migraine headaches and is generally well tolerated.