A randomized trial of divalproex sodium extended-release tablets in migraine prophylaxis.
OBJECTIVE
To evaluate the efficacy and safety of extended-release divalproex sodium compared with placebo in prophylactic monotherapy treatment of migraine headache.


METHODS
This was a double-blind, randomized, placebo-controlled, parallel-group study. Subjects with more than two migraine headache attacks during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to receive either extended-release divalproex sodium or matching placebo once daily for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and the dose was then increased to 1,000 mg once daily with an option, if intolerance occurred, to permanently decrease the dose to 500 mg during the second week. Reduction from baseline in 4-week migraine headache rate was the primary efficacy variable. Migraine headaches separated by a < 24-hour headache-free interval were counted as single migraines in calculating migraine headache rates. Tolerance and safety were also evaluated.


RESULTS
The mean reductions in 4-week migraine headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo group (p = 0.006); reductions with extended-release divalproex sodium were significantly greater than with placebo in all three 4-week segments of the treatment period. No significant differences were detected between treatment groups in either the overall incidence or in the incidence of any specific treatment-emergent adverse event; 8% of subjects treated with extended-release divalproex sodium and 9% of those treated with placebo discontinued for adverse events.


CONCLUSIONS
Extended-release divalproex sodium is an efficacious, well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine medication.
Freitag
Frederick G
FG
Diamond Headache Clinic, 467 W. Deming Place, Chicago, IL 60614, USA.
Collins
S D
SD
Carlson
H A
HA
Goldstein
J
J
Saper
J
J
Silberstein
S
S
Mathew
N
N
Winner
P K
PK
Deaton
R
R
Sommerville
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D018682:GABA Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy* / Q000517:prevention & control*; D014635:Valproic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
D003692:Delayed-Action Preparations; D018682:GABA Agents; D014635:Valproic Acid