Valproic acid is effective in migraine prophylaxis at low serum levels: A prospective open-label study

Objective.-We evaluated the efficacy of prophylactic valproic acid treatmen t (6 months) on the frequency of migraine attacks and the number of migrain e 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-adjus ted studies have recommended valproic acid doses within a range of 500 to 1 500 mg per day for migraine prophylaxis. Design and Methods.-In this prospective open-label study, 52 patients recei ved valproic acid doses of 300 to 1-200 mg per day; 45 patients were treate d per protocol. Valproic acid serum levels increased linearly in relation t o the valproic acid dose and were between 21 and 107 mug/mL at the end of t he treatment period. Patients were divided into two groups: those with valp roic acid serum levels less than 50 mug/mL, (group 1) and those with serum levels greater than 50 mug/mL (group 2). Results.-The frequency of migraine attacks was significantly reduced in gro up 1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache d ays 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 mouth) was observed. The outcome of group 1 (low serum level) was significantly better than that of group 2 with resp ect to both parameters (P < .05). Side effects were generally mild and temp orary. Conclusions.-Due to the lack of additional benefit from higher valproic aci d 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 mug/mL for the prop hylactic treatment of migraine.