Topiramate in the treatment of partial and generalized epilepsy

Topiramate (TPM) is a widely-used drug for the treatment of epilepsy. It is useful for several types of partial-onset and generalized-onset seizures, and is therefore considered a broad-spectrum agent. It is also effective as a prophylactic against migraine headaches. TPM was first approved for prescription use in 1996. In various countries it is now approved for adjunctive and monotherapy of partial-onset seizures and for therapy of generalized tonic-clonic seizures of nonfocal origin, for children and adults. For initial monotherapy of new-onset seizures, a target dose of 100 mg/day for adults is recommended. Adjunctive use with enzyme-inducing drugs and use for refractory seizures requires higher dosages, though the optimum dose for most patients does not exceed 400 mg/day. Excretion is primarily renal and TPM is not a significant hepatic enzyme inducer. Although it is usually safe and well-tolerated, adverse effects limit use in about 25% of patients. The most salient of these is cognitive dysfunction, especially problems with expressive speech and verbal memory. Weight loss, renal stones, paresthesias and other central nervous system side effects may occur. Tolerability is improved by low initial doses and slow titration to effect.