TOPIRAMATE - A NEW ANTIEPILEPTIC DRUG

OBJECTIVE: To review proposed mechanisms of action, clinical pharmacol ogy, efficacy, safety, and tolerability of the antiepileptic drug (AED ) topiramate. METHODS: All available data from the clinical developmen t program -published and unpublished data (provided by investigators o r the RW Johnson Pharmaceutical Research institute)-were analyzed, wit h emphasis on the results of double-blind, placebo-controlled trials. Data from open-label studies provided information about long-term effi cacy and tolerability, FINDINGS: Topiramate is highly effective in the control of previously therapy-resistant partial seizures, with or wit hout secondary generalization in the refractory adult patient populati on enrolled in controlled clinical trials, seizures were reduced by 50 % or more in 27-47% of patients compared with 0-18% in placebo-treated patients and by 75% or more in 9-36% of the patients compared with 0- 9% of those receiving placebo. The most common adverse effects involve the central nervous system and are mild to moderate in nature. Advers e effects include somnolence, fatigue, psychomotor slowing, and concen tration problems. Thr currently recommended dosing is lower and titrat ion slower than schedules used in the clinical trials; this may improv e the tolerability of topiramate. Topiramate has few interactions with currently available AEDs, but phenytoin concentrations increased in s ome patients, Topiramate can be used initially as adjunctive therapy. Plasma topiramate concentrations are reduced substantially when used w ith enzyme-inducing AEDs. Open-label data and a single double-blind tr ial suggest that topiramate monotherapy may be effective. Open-label d ata also indicate that topiramate may be effective in generalized seiz ures of nonfocal origin, including those associated with Lennox-Gastau t syndrome. CONCLUSIONS: The robust clinical effects of topiramate exp and the therapeutic options for patients with epilepsy, Controlled cli nical trials are needed to verify initial observations that topiramate may be effective against a broad spectrum of seizure types and to dir ectly compare efficacy and tolerability with other new and standard AE Ds.