Safety of divalproex sodium in migraine prophylaxis: an open-label, long-term study. Long-term Safety of Depakote in Headache Prophylaxis Study Group.
BACKGROUND
The adverse event profile of long-term divalproex therapy for epilepsy is well established, but little is known about the tolerability or safety of divalproex in long-term migraine prophylaxis.


OBJECTIVE
Evaluate the long-term safety and efficacy of divalproex sodium in migraine prophylaxis.


METHODS
Open-label, long-term study, of up to 3 years, of patients who completed one of two multicenter, double-blind, randomized, placebo-controlled studies.


METHODS
Eighteen headache/neurology centers throughout the United States.


METHODS
One hundred sixty-three patients: 46 treated with placebo, 117 treated with divalproex for migraine in previous studies.


METHODS
Divalproex therapy initiated at 500 mg/day (250 mg twice daily), with adjustment in dose and dosing frequency possible after 1 to 3 days.


METHODS
Number and proportion of patients reporting treatment-emergent adverse events, prevalence and incidence for each treatment-emergent adverse event, vital signs, body weight, 4-week migraine rates and proportion of patients with 50% or greater reduction in rate over time.


RESULTS
Treatment lasted more than 180 days for 71% of patients and more than 360 days for 48% of patients. Improvements in the 4-week, change-from-baseline migraine rates were seen during each of the 3- and 6-month time intervals.


CONCLUSIONS
Divalproex is effective for migraine prophylaxis, and initial benefits are maintained for periods in excess of 1080 days.
Silberstein
S D
SD
Jefferson Headache Center, Thomas Jefferson University, 111 South 11th Street, Suite 81309, Philadelphia, PA 19107, USA.
Collins
S D
SD
D000328:Adult; D000368:Aged; D005260:Female; D018682:GABA Agents / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012449:Safety; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D018682:GABA Agents; D014635:Valproic Acid