Anti-epileptic drugs in the preventive treatment of migraine headache: a brief review

Anti-epileptic drugs are employed for the prophylactic treatment of migraine. Valproic acid and its sodium salt (divalproex) have been shown to be effective in preventing migraine in double-blind placebo-controlled studies. Gabapentin and lamotrigine have also been proposed for migraine prophylaxis, but more extensive studies are needed to confirm their efficacies. The main mechanism of action of anti-epileptic drugs in the inhibition of the sodium channel to induce a depolarization, preventing the high, frequent action potentials typically excited by convulsive attacks. Moreover, valproate and gabapentin increase brain concentrations of GABA and, probably, inhibit the degradation of GABA. Other proposed mechanisms of action for valproate are a direct effect on neuronal membranes and a reduction of excitatory transmission by aspartate. Valproate, at the recommended dose of 500 mg twice daily, is well tolerated. The more frequent unwanted effects associated with almost all drugs of this class are weight gain, drowsiness, dizziness and tremor. Topiramate has recently been proposed for the treatment of unresponsive, high frequency migraine, taking into account both the GABA and glutamatergic mechanisms of action. Received: 13 November 2000 / Accepted in revised form: 5 April 2001