MIGRAINE PROPHYLAXIS WITH DIVALPROEX

Objective: To compare the effectiveness and safety of divalproex sodiu m (Depakote) and placebo in the prophylaxis of migraine headache. Desi gn: Multicenter, double-blind, randomized, placebo-controlled investig ation, having a 4-week, single-blind placebo baseline phase and a 12-w eek treatment phase (4-week dose adjustment, 8-week maintenance). Sett ing: Eight headache/neurology clinics throughout the United States. Pa tients: One hundred seven patients randomized to divalproex or placebo (2:1 ratio): 70 receiving divalproex and 37 receiving placebo. Interv ention: Divalproex and placebo dosages titrated in blinded fashion dur ing dose adjustment period to achieve actual/sham trough valproate sod ium concentrations of approximately 70 to 120 mg/L. Measurements and M ain Results: During the treatment phase, the mean migraine headache fr equency per 4 weeks was 3.5 in the divalproex group and 5.7 in the pla cebo group (P less than or equal to.001), compared with 6.0 and 6.4, r espectively, during the baseline phase. Forty-eight percent of divalpr oex-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-treate d patients reported significantly less functional restriction than pla cebo-treated patients and used significantly less symptomatic medicati on per episode. No significant treatment group differences were observ ed in average peak severity or duration of individual migraine headach es. Treatment was stopped in 13% of divalproex-treated patients and 5% of placebo-treated patients because of intolerance (P, not significan t). Conclusions: Divalproex is an effective prophylactic drug for pati ents with migraine headaches and is generally well tolerated.