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

Headache. 2001 Sep;41(8):774-8. doi: 10.1046/j.1526-4610.2001.01142.x.

Abstract

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 microg/mL at the end of the treatment period. Patients were divided into two groups: those with valproic acid serum levels less than 50 microg/mL (group 1) and those with serum levels greater than 50 microg/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 microg/mL for the prophylactic treatment of migraine.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial

MeSH terms

  • Anticonvulsants / administration & dosage*
  • Anticonvulsants / blood*
  • Anticonvulsants / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Migraine Disorders / prevention & control*
  • Prospective Studies
  • Valproic Acid / administration & dosage*
  • Valproic Acid / blood*
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Valproic Acid