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Keywords:

  • migraine;
  • prevention;
  • basic mechanisms;
  • drug development

A variety of drugs from diverse pharmacological classes are in use for migraine prevention. Traditionally, they have been discovered by serendipity. Examples include β-adrenergic blockers, anticonvulsants, tricyclic antidepressants, and serotonin receptor antagonists. The mechanisms of action of migraine preventive drugs are multiple but it is postulated that they converge on two targets: (1) inhibition of cortical excitation; (2) restoring nociceptive dysmodulation. The antiepileptic drugs (e.g., topiramate, valproate, gabapentin), calcium channel blockers such as verapamil, and inhibitors of cortical spreading depression are some examples of drugs that reduce neuronal hyperexcitability. On the other hand, modulators of the serotonergic and adrenergic systems and cholinergic enhancing drugs may restore descending nociceptive inhibition and play a role in migraine prevention. To date, Level 1 evidence and clinical experience favor the use of the antidepressant amitriptyline, the anticonvulsants divalproex and topiramate, and the β-adrenergic blockers propranolol, timolol and metoprolol as first line migraine preventive drugs. The evidence for others (e.g., verapamil) is not as strong. Migraine preventive drugs have varying degrees of adverse effects, some of which could be limiting, and their efficacy should balanced with their risks of adverse effects, patients' expectations and desires, and compliance. It is hoped that future migraine preventive drugs target migraine mechanisms more specifically, which could well enhance the therapeutic index.