LAMOTRIGINE VERSUS PLACEBO IN THE PROPHYLAXIS OF MIGRAINE WITH AND WITHOUT AURA

Lamotrigine blocks voltage-sensitive sodium channels, leading to inhib ition of neuronal release of glutamate. Release of glutamate may be es sential in the propagation of spreading cortical depression, which som e believe is central to the genesis of migraine attacks. This study co mpared safety and efficacy of lamotrigine and placebo in migraine prop hylaxis in a double-blind randomized parallel-groups trial. A total of 110 patients entered; after a 1-month placebo run-in period, placebo- responders and non-compliers were excluded, leaving 77 to be treated w ith lamotrigine (n=37) or placebo (n=40) for up to 3 months. Initially , lamotrigine therapy was commenced at the full dose of 200 mg/day, bu t, following a high incidence of skin rashes, a slow dose-escalation w as introduced: 25 mg/day for 2 weeks, 50 mg/day for 2 weeks, then 200 mg/day. Attack rates were reduced from baseline means of 3.6 per month on Iamotrigine and 4.4 on placebo to 3.2 and 3.0 respectively during the last month of treatment. Improvements were greater on placebo and these changes, not statistically significant, indicate that Iamotrigin e is ineffective for migraine prophylaxis. There were more adverse eve nts on Iamotrigine than on placebo, most commonly rash. With slow dose -escalation their frequency was reduced and the rate of withdrawal for adverse events was similar in both treatment groups.