A comparison of divalproex with propranolol and placebo for the prophylaxis of migraine without aura
R. G. Kaniecki
Allegheny General Headache Center, Allegheny University of the Health Sciences, Pittsburgh, Pa., USA.
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 divalproex-treated, 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.
