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Can Valproate Prevent Migraine Headaches?

Objective: To investigate the effectiveness of valproate in the prevention of migraine headaches. The drug has been approved by the FDA for migraine prophylaxis in addition to its primary use in seizure control. Data Sources: A MEDLINE search (1988–1995) of the English-language literature pertaining to the use of valproate for prophylaxis of migraine headaches was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. Study Selection and Data Extraction: All articles were considered for possible inclusion in the review. Pertinent information was selected for discussion. Data Synthesis: Results of five clinical studies carried out worldwide were reviewed: a historical study of 22 patients from Denmark and studies of 32 patients in Israel, 43 patients in Denmark, 75 patients in California, and 117 patients in the US. Eleven patients (50%) were free of headache in the first study. The number of migraine attacks decreased from 15.5 to 8.8 in the second study, whereas patients treated with valproate reported 3.5 days with migraine versus 6.1 for patients receiving placebo in the third study. Efficacy rates of 85% and 61% were seen for patients with frequent migraine and transformed migraine, respectively, in the fourth study, and 48% of patients treated with divalproex compared with 14% of patients receiving placebo showed at least a 50% reduction in migraine headache frequency in the fifth study. Conclusions: Approximately half of the patients were shown to experience roughly a 50% reduction in the number of migraine attacks or days with migraine headaches; thus, valproate appears to provide a therapeutic alternative for patients who do not respond to or cannot tolerate beta-receptor blockers, tricyclic antidepressants, or calcium-channel blockers for prophylaxis of migraine headaches.