TOPIRAMATE - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES AND CLINICAL EFFICACY IN THE MANAGEMENT OF EPILEPSY

Topiramate is a sulphamate-substituted monosaccharide derived from D-f ructose and is structurally unrelated to other antiepileptic drugs. It acts by multiple mechanisms that suggest it may be effective in sever al types of epilepsy. In double-blind placebo-controlled trials, add-o n therapy with topiramate 400 to 1000 mg/day reduces the seizure rate by greater than or equal to 50% in 35 to 52% of adult patients with re sistant partial epilepsy (with or without secondarily generalised seiz ures) compared with 0 to 19% of placebo recipients; a 200 mg/day dosag e was less effective. Topiramate has also been shown to be superior in efficacy to placebo in well controlled trials in patients with genera lised tonic-clonic seizures, Lennox-Gastaut syndrome and in paediatric patients with partial epilepsy. Efficacy has been maintained for 7 ye ars and some patients may also be satisfactorily treated with topirama te monotherapy. Further study is needed to follow up on the promising results of topiramate use in other paediatric epilepsies. Adverse CNS events are the most common untoward effects during topiramate therapy and are most likely to lead to withdrawal of the drug. However most ad verse events are mild to moderate in severity and lessen with continue d drug therapy. In clinical trials, most adverse events which were dos e limiting or led to discontinuation of treatment occurred during the titration phase. The overall incidence of adverse events may be reduce d by slower upward dosage titration.In summary, topiramate appears to be a suitable agent for add-on therapy in adult patients with partial epilepsy. Preliminary reports support the use of add-on topiramate in adults with generalised epilepsy, in childhood epilepsies and in patie nts with Lennox-Gastaut syndrome, as well as the use of topiramate mon otherapy in patients with partial epilepsy. Thus, topiramate can be co nsidered an important new drug for the management of patients with ref ractory epilepsy.