Zonisamide for Migraine Prophylaxis in Patients Refractory to Topiramate

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Topiramate is a sulfamate-substituted monosaccharide that has proven efficacy in reducing migraine attacks frequency and severity and has similar mechanisms of action and side effects profile to zonisamide. Although there are some studies suggesting a potential role of this drug in migraine prophylaxis, data are still scarce. We evaluate the efficacy and safety of zonisamide for migraine prevention in patients refractory to topiramate.


Sixty-three patients were initiated on 50 mg/d zonisamide dosage, which was titrated to 400 mg/d, as tolerated. Number of migraine attacks, headache severity (according to a 1- to 10-point visual analog scale), and use of acute medication were tested before and 2 and 6 months after the initiation of zonisamide. Demographic data, dose of the medication, duration of the treatment, and adverse events were also collected and analyzed.


Statistically significant improvement in number of migraine attacks, headache severity, and use of acute medication reduction was obtained after the second month of zonisamide therapy and carried through month 6 of treatment. Fifteen patients reported adverse events, the most common of which was concentration difficulties.


These results suggest that zonisamide is effective and well tolerated for migraine prevention in patients refractory to topiramate. With the exception of the inhibition of T-type calcium channels by zonisamide, its mechanisms of action seem to be very similar to topiramate's. We suggest the potential role of these channels in the pathophysiology of migraine.

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