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New and Emerging Prophylactic Agents for Migraine
Krymchantowski AV, Bigal ME, Moreira PF
Posted: April 2003  
CNS Drugs 2002; 16:611-634

Frequent, severe, and long-lasting migraine attacks require prophylaxis. Established drugs used for the prevention of migraine such as beta-adrenoceptor antagonists (beta-blockers), calcium channel antagonists, antidepressants, and others have an unknown mode of action in migraine. Their prophylactic effect in migraine was discovered by chance in clinical practice when these drugs were used for other purposes.

Recent research into the mechanisms of migraine have progressively recognized that cortical hyperexcitability and an imbalance between neuronal inhibition and excitation may play an important role in migraine pathophysiology. This has led to the identification of potential new agents for the prevention of migraine attacks. This paper reviews the recent literature on these new agents.

After analyzing the available controlled and uncontrolled clinical studies as well as abstracts, divalproex sodium can be recommended for the prevention of migraine. Lamotrigine may be useful for preventing aura associated with migraine, and topiramate seems a promising option pending trials with more patients, which are currently underway. Riboflavin (which is possibly involved in improving neuronal energy production) appears to be a promising agent, although comparisons with established prophylactic medications are needed. Gabapentin, magnesium, lisinopril, and botulinum toxin A have recently been suggested to be effective. At present;, however, there are insufficient rigorous and reliable controlled data on these drugs for them to be indicated for such use. Emerging options such as tiagabine, levetiracetam, zonisamide, and petasites may all be useful, but controlled data are required to confirm their efficacy. The anti-asthma medication montelukast was found to be effective in an open trial, but ineffective in a recently completed controlled trial.

There is an expectation that modern neuroscience will soon provide more efficacious and better tolerated prophylactic medications for migraine.