Objective
To compare the efficacy of divalproex sodium (Depakote) with that of propranolol hydrochloride (and placebo) for the prophylaxis of migraine without aura.
Design
Single-investigator, randomized, single-blind, placebo-controlled study with 5 phases: baseline (weeks 1-4); placebo (weeks 5-8); first treatment, 1 agent (weeks 9-20); washout (weeks 21-24); and second treatment, crossover to other agent (weeks 25-36).
Setting
Private practice of a general neurologist with a special interest in headache disorders.
Patients
Of 37 patients (30 women and 7 men) selected, 32 completed the study. All received placebo, after which half were randomized to receive divalproex or propranolol, then crossed over after washout.
Intervention
Divalproex and propranolol doses were titrated during the initial 8 weeks of each 12-week treatment cycle. For divalproex, doses were titrated to 1500 mg/d in 23 patients, to 2000 mg/d in 2, and downward in 7; the mean valproate sodium trough level was 68.5 mg/L. Propranolol was titrated to 180 mg/d in 28 patients, to 240 mg/d in 1, and downward in 3.
Results
Migraine frequency was reduced in 19% (6/32) of placebo-treated, 66% (21/32) of divalproextreated, and 63% (20/32) of propranolol-treated patients. Assessment of migraine-days per month revealed significant response to placebo in 22% (7/32) of patients, to divalproex in 66% (21/32), and to propranolol in 69% (22/32). When results were limited to the third month of each active-agent treatment phase, 75% (24/32) of patients receiving divalproex and 78% (25/32) of those receiving propranolol had reduction in migraine frequency.
Conclusion
No significant difference was identified between divalproex and propranolol for the prophylaxis of migraine without aura.
