Antiepileptic drugs in the treatment of headache: Neuroprotective effect or something else?

The hypothesis that cortical hyperexcitability may play an important role in the physiopathology of migraine has lead to the therapeutic use of antiepileptic drugs in headache prophylaxis. Cortical hyperexcitability is due to an imbalance between neuronal inhibition, mediated by gamma-aminobutyrric acid (GABA), and neuronal excitement, mediated by excitatory aminoacids. It becomes therefore clear how cortical excitability may be modulated by acting on mechanisms such as the synthesis and metabolism of GABA and on targets such as GABA and glutamate receptors and on sodium and calcium channels. The question is, whether, thanks to their tolerability and rapidity of action, these should be considered as first-choice prophylaxis drugs rather than simply as alternative drugs. Thanks to their action on the key-mechanisms implicated in the genesis and maintenance of pain, valproic acid, gabapentin, topiramate, levetiracetam and lamotrigine have all the requisites in terms of efficacy, tolerability and rapidity of action that are requested from a drug in order to be considered a firstchoice drug rather than simply an alternative to the drugs currently used. The expansion, however, of medical areas in which antiepileptic drugs are prescribed and the growing number of patients using them, require an increased sensitivization in order to avoid their incorrect use.