Topiramate (Topamax) has been registered since July 1998 and has market authorization for the Federal Republic of Germany as an additive drug for the treatment of patients (age 12 or older) suffering from intractable partial and secondarily generalized seizures. The anticonvulsant effect of topiramate is based on three mechanisms: (a) modulating the blocking of the Na channels activated by voltage, depending on status, (b) potentiation of GABAA-mediated inhibiting neurotransmission, and (c) inhibition of excitatory neurotransmission by blocking APMA glutamate receptors. Topiramate exhibits a substantial anticonvulsive effect on partial seizures both with and without secondary generalization. The median reduction in seizure frequency using topiramate as adjunct therapy was 44%. In 44% of patients, seizure frequency was reduced by more than 50%, and seizure reduction was more than 75% in nearly half of these (i.e., in 21% of all patients), while 5% of patients remained completely free of seizures. Adverse events most often caused central nervous disturbances. Weight loss, the development of renal calculi, and impairment of cognitive functions may occur. It is recommended to start therapy with topiramate at a daily dosage of 25 mg, increasing by 25 mg every week up to 200-400 mg/day but not exceeding 1000 mg/day.
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