(1) The first-line treatment for patients with
partial epilepsy is
carbamazepine monotherapy. Second-line options include monotherapy with
valproic acid,
gabapentin,
lamotrigine or
oxcarbazepine. Other
antiepileptics are also available for combination
therapy of refractory
partial epilepsy. (2)
Zonisamide is a sulphonamide derivative that inhibits
carbonic anhydrase; it resembles
topiramate, a
drug already approved for use for this indication in the European Union. (3) The main clinical trial, a double-blind study lasting 36 weeks, compared the addition of
zonisamide or placebo to ongoing treatment in 351 patients with refractory
partial epilepsy. The "response rate" (the proportion of patients with at least a 50% reduction in the frequency of
seizures) was significantly higher with
zonisamide plus the previous treatment than with placebo plus the previous treatment (46.6% versus 17.6%). An indirect comparison suggests that this is no better than treatment with a second-line
antiepileptic drug. (4) Results of three other placebo-controlled trials of third-line combinations in a total of 499 patients treated for 12 weeks were similar. (5) The main adverse effects of
zonisamide are those typically seen with
topiramate: neuropsychological disorders and disorders due to
carbonic anhydrase inhibition (
kidney stones, reduced perspiration, and
hyperthermia). There are various other adverse effects, including a risk of severe
skin rash. (6) The profile of interactions is complex. There is a risk of pharmacokinetic interactions, and of pharmacodynamic interactions with other
carbonic anhydrase inhibitors. (7) In France, treatment with
zonisamide costs nearly 20 times more than treatment with
carbamazepine or
valproic acid. (8)
Zonisamide has no therapeutic advantages over other
antiepileptics available for combination
therapy of
partial epilepsy.