Central mechanisms of controlled-release metoprolol in migraine: a double-blind, placebo-controlled study

beta-Blockers are widely used in the prophylaxis of migraine and have been described as very effective drugs in many studies. Some investigators have demonstrated that the clinical improvement of migraine corresponds to the normalization of the contingent negative variation (CNV), a slow cortical potential measuring cortical information processing. However, most of these studies have contained a variety of methodological pitfalls, which we attempted to address in the current study. Twenty patients suffering from migraine without aura were randomly divided into two groups. The groups were treated either with controlled-release metoprolol or placebo for 3 months, using a double-blind design. Twice before and once after each month of the treatment the CNV was recorded. After 3 months, a significant reduction of migraine frequency, duration and intensity was demonstrated for the metoprolol compared with the placebo group. The CNV was characterized by a marked reduction of the amplitude of the total CNV and postimperative negative variation and normalization of the eartly CNV habituation following treatment. Therefore, metoprolol may exert its prophylactic effect in migraine through the influence on cortical information processing and excitability represented by the CNV.