In a double-blind, randomized, parallel-group trial, we compared topiramate (TPM) with placebo as add-on therapy in patients with refractory partial epilepsy. TPM was titrated either to the target dosage of 800 mg/ day [400 mg twice daily (b.i.d)] or to the maximal tolerated dose if lower. Twenty-eight (28) patients were randomized to each treatment group. In the intent-to-treat analysis, the net median percent reduction relative to placebo in average monthly seizure rate was 54% for patients in the TPM group (p < 0.001). None of the placebo-treated patients and 43% of the patients treated with TPM experienced > or = 50% reduction in seizures (p = 0.001), and 36% of patients assigned to TPM had a 75-100% reduction in seizures (p < 0.01). Secondarily generalized seizures were also significantly reduced in the TPM group (p = 0.044). The most common adverse events (AE) reported in the TPM group were fatigue, impaired concentration, weight loss, dizziness, and paresthesias. AE occurring either during the rapid titration of TPM or at high dosages led 21% of TPM-treated patients to withdraw from the study. Half of these occurred during the titration study period. No serious AE or clinically important changes in clinical laboratory measures were observed. The present study further establishes the favorable profile and good benefit/risk ratio of TPM in resistant partial epilepsy.
The results of the present trial indicate that TPM 600 mg/day is effective in the treatment of refractory partial-onset seizures with or without secondarily generalized seizures.
Results of clinical and pharmacokinetic observations on sodium valproate (VPA) are reported from a long-term study in 100 children with epilepsy. VPA is the drug of choice in patients with absences. VPA may preferably be chosen as the first drug in patients with atonic seizures partly because all treatment of these seizures is uncertain, and the effect of VPA may be striking, without side effects. When starting with VPA the great problem of drug interactions is avoided. Treating patients with intractable epilepsy has shown that VPA may be effective in all seizure types regardless of the EEG-findings. However, generalized paroxysms of spike and wave complexes in the EEG are a good prognostic sign especially when fairly regular. Side effects are few when using enteric coated tablets, but toxic effects may be serious. Control schemes of blood and liver functions are necessary. Drug fasting serum level monitoring is mandatory, especially when VPA is given in combination with other anti-epileptic drugs as interactions with these are pronounced. Optimal clinical effect is usually seen on serum levels between 300 and 600 microgram mol/l, which may be obtained by giving 10-20 mg/kg daily assuming that the patient is receiving VPA monotherapy, which should always be aimed at. Comedication may have to be withdrawn to obtain therapeutic serum levels of VPA due to drug interactions.
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