Migraine prophylactic drugs - something new under the sun?

INTRODUCTION: The development of preventive treatments for migraine has lagged behind, in part because of limited knowledge about the primum movens of attacks. AREAS COVERED: We aimed to make a status report about newer preventive drugs for migraine, mainly by reviewing ongoing studies and their potential mechanism of action. An overview of published and unpublished trials was obtained from electronic databases focusing on randomized controlled trials (RCTs) published or initiated during the last 3 years. Drugs inhibiting cortical spreading depression and calcitonin gene-related peptide antagonist, which mainly acts vasoconstrictive, seem promising, but need further exploration. The use of nitric oxide blockers and drugs modifying excitatory brain activity such as glutamate antagonists and newer antiepileptics have so far not been successful. Drugs such as melatonin, vitamin E and botulinum toxins aiming for other targets seem to have no or marginal effect. EXPERT OPINION: The results from Phase II studies with newer prophylactic drugs for migraine targeting binding sites in the brain are conflicting, but they may have potential for clinical use. No major breakthrough in migraine prevention can be expected from the ongoing trials, but further insight into the effect on migraine subtypes is anticipated.