Study funded by Abbott, Abbott Park IL.
Safety and Tolerability of Divalproex Sodium Extended-Release in the Prophylaxis of Migraine Headaches: Results of an Open-Label Extension Trial in Adolescents
Article first published online: 10 NOV 2008
© 2008 the Authors. Journal compilation © 2008 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 49, Issue 1, pages 36–44, January 2009
How to Cite
Apostol, G., Pakalnis, A., Laforet, G. A., Robieson, W. Z., Olson, E., Abi-Saab, W. M. and Saltarelli, M. (2009), Safety and Tolerability of Divalproex Sodium Extended-Release in the Prophylaxis of Migraine Headaches: Results of an Open-Label Extension Trial in Adolescents. Headache: The Journal of Head and Face Pain, 49: 36–44. doi: 10.1111/j.1526-4610.2008.01299.x
Conflict of Interest: All authors except Dr. Pakalnis are employees of Abbott.
- Issue published online: 5 JAN 2009
- Article first published online: 10 NOV 2008
- Accepted for publication August 9, 2008.
- pediatric migraine;
- divalproex sodium;
- migraine prophylaxis;
Objective.— To evaluate the long-term safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches in adolescents.
Background.— Divalproex sodium has been approved for migraine prophylaxis in adults. A previous double-blind, placebo-controlled study of the efficacy and safety of divalproex sodium extended-release for prevention of migraine in adolescents was followed by the present long-term extension trial, which was designed to collect additional safety and tolerability data.
Methods.— This was a 12-month, Phase 3, open-label extension of a 3-month, double-blind, placebo-controlled, multicenter study of adolescents aged 12 to 17 years with migraine headaches who had either completed the previous study or had discontinued because of lack of efficacy. Subjects from the previous trial who had experienced serious adverse events possibly or probably related to study drug were excluded. Divalproex sodium extended-release 500 mg daily was administered for 15 days then increased to 1000 mg. Study visits were conducted at days 1 and 15 and months 1, 2, 3, 6, 9, and 12. Safety assessments included adverse event collection, laboratory testing, physical and neurological examinations, vital signs, and electrocardiograms, as well as reproductive endocrine analyses for postmenarchal female subjects. Efficacy was evaluated by sequential 4-week migraine headache rates calculated from subjects' headache diaries.
Results.— A total of 112 subjects enrolled in the trial. The most common adverse events were weight gain (15%), nausea (14%), somnolence (12%), upper respiratory tract infection (11%), increased ammonia (8%), and sinusitis (8%). Five (4%) subjects experienced serious adverse events, and 15 (13%) subjects prematurely discontinued because of an adverse event. Increased ammonia levels were noted in some individuals, and the mean ammonia level for all subjects increased 19.2 µm from baseline. No other clinically significant changes were observed in laboratory values, vital signs, or electrocardiograms. Improvement in mean and median 4-week migraine headache rates occurred by the fourth month and lasted for the duration of the trial.
Conclusions.— In this long-term open-label extension study, the safety profile of divalproex sodium extended-release in adolescents with migraine was consistent with that observed in the preceding 3-month, double-blind trial and in previous adult studies. Overall, divalproex sodium extended-release was well-tolerated in adolescents aged 12 to 17 years.