Valproic Acid Is Effective in Migraine Prophylaxis at Low Serum Levels: A Prospective Open-Label Study


Address all correspondence to Dr. Guy Arnold, Department of Neurology, Charité Clinic, Humboldt University of Berlin, Schumannstraße 20/21, D-10117 Berlin, Germany.


Objective.—We evaluated the efficacy of prophylactic valproic acid treatment (6 months) on the frequency of migraine attacks and the number of migraine headache days with respect to serum levels.

Background.—Valproic acid, a GABAergic drug, has been shown to be effective for migraine prophylaxis. Results from several dose- and serum level-adjusted studies have recommended valproic acid doses within a range of 500 to 1500 mg per day for migraine prophylaxis.

Design and Methods.—In this prospective open-label study, 52 patients received valproic acid doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic acid serum levels increased linearly in relation to the valproic acid dose and were between 21 and 107 μg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 μg/mL (group 1) and those with serum levels greater than 50 μg/mL (group 2).

Results.—The frequency of migraine attacks was significantly reduced in group 1 from 3.5 ± 0.9 to 2.0 ± 0.9 attacks per month. Migraine headache days also decreased (6.4 ± 3.5 to 4.6 ± 2.9 days per month). In the high serum level group, a reduction of migraine attacks from 3.5 ± 0.9 to 2.8 ± 1.0 attacks per month and only a slight decrease in headache days (6.4 ± 3.5 to 6.1 ± 2.4 days per month) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with respect to both parameters (P<.05). Side effects were generally mild and temporary.

Conclusions.—Due to the lack of additional benefit from higher valproic acid doses (more than 600 mg per day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum level less than 50 μg/mL for the prophylactic treatment of migraine.