Topiramate in migraine prevention

Abstract

Migraine is a common episodic headache disorder characterized by attacks that consist of various combinations of headache and neurologic, gastrointestinal and autonomic symptoms. Migraine with aura may be due to neuronal hyperexcitability, perhaps from cortical disinhibition. It is likely that headache results from the activation of meningeal and blood vessel nociceptors combined with a change in central pain modulation. Antiepileptic drugs are increasingly being recommended for migraine prevention since placebo-controlled, double-blind trials prove them to be effective. Topiramate is a structurally unique antiepileptic drug that was discovered by serendipity. It is a derivative of the naturally occurring monosaccharide D-fructose and contains sulfamate functionality. Topiramate may bind to membrane channel complexes at phosphorylation sites in the inner loop and, thereby, allosterically modulate ionic conductance through the channels. The topiramate MIGR-001, MIGR-002 and MIGR-003 trials represent the largest controlled trials of a migraine preventive agent ever performed. Treatment with 100 or 200 mg/day of topiramate was associated with significant reductions in migraine frequency, migraine days and the number of migraine attacks per month. Topiramate was also associated with a reduced use of acute medications. The most common adverse events were difficulty with concentration and attention, difficulty with memory, mood problems, anorexia and weight loss, paresthesias, hypoesthesia and language problems. Topiramate is a first-line migraine preventive drug and should be considered preferentially for all patients in whom weight gain is a concern, who are currently overweight or who have coexistent epilepsy or bipolar disease.