Epilepsia
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Meta Analysis
Clinical administration of new antiepileptic drugs: an overview of safety and efficacy.
Gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin, and zonisamide are all administered as add-on therapy for treatment of patients with refractory epilepsy. To date, no comparative randomized trials have been performed that could potentially allow an evidence-based choice to be made between these antiepileptic drugs (AEDs). We report a series of meta-analyses of placebo-controlled, randomized add-on trials in patients with partial epilepsy. ⋯ When each outcome is compared among drugs, the 95% CIs overlap. Therefore, no conclusive evidence of a difference in efficacy or tolerability between these AEDs was derived, even though the apparently most effective agent (topiramate) may be twice as effective as the apparently least effective agent (lamotrigine). Comparative randomized studies are needed to further evaluate these drugs.
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We define intractable in the first 5 years of epilepsy treatment as an average of at least one seizure every 2 months. For the longer term, we define intractable as at least one seizure per year. Population studies from Chicago, IL, U. ⋯ Intractable epilepsy is rare. Careful definition of the characteristics of children with intractable epilepsy who do respond completely to new AEDs will likely provide the only rational approach to treatment of children with three drug failures. Collaboration by multiple epilepsy centers will be required to gain this information.
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Status epilepticus (SE) is one of the most common neurologic emergencies in children, adolescents, and young adults. SE may be due to acute neurologic conditions such as meningitis, encephalitis, or stroke, complicated febrile seizures, intractable epilepsy, degenerative diseases, intoxication, or may be the first manifestation of epilepsy. Initial treatment of convulsive SE is usually with an intravenous benzodiazepine (BZD) [lorazepam (LZP) or diazepam (DZP)], phenobarbital (PB), or phenytoin (PHT). ⋯ Epilepsia partialis continua (EPC) is almost always due to an acute or chronic destructive lesion. Surgical treatment may be the only effective modality in some children with EPC. Acute treatment of breakthrough seizures and clusters of seizures at home with rectal BZDs (usually DZP, 0.2-0.5 mg/kg) may prevent progression to SE in some children and adolescents and reduce the need for visits to emergency facilities.
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This article surveys the pharmacokinetic parameters for the new antiepileptic drugs (AEDs): felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin. Compared to the pharmacokinetics of standard AEDs, these new AEDs have progressed in terms of (a) longer half-lives, permitting once- or twice-daily dosing, (b) greatly reduced potential for drug interactions, thus increasing ease of treatment, and (c) general lack of hepatic enzyme induction, which facilitates polytherapy as well as other aspects of treatment.
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In separate studies, potential pharmacokinetic interactions of topiramate (TPM) with phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) were evaluated. TPM was added to the baseline antiepileptic drug (AED) at a dosage of up to 800 mg/day, after which the baseline drug was discontinued, when possible. Addition of TPM produced no change in plasma levels of CBZ or CBZ epoxide (CBZ-E). ⋯ The risk for clinically meaningful changes in plasma levels of traditional AEDs when TPM is added to or discontinued from concomitant regimens appears to be minimal. However, adjustments in TPM dosages are likely to be needed when potent enzyme inducers, such as PHT or CBZ, are added or discontinued. TPM has a relatively low propensity for clinically significant drug interactions, and its pharmacokinetic and drug interaction profiles represent a clear advance over those of the traditional AEDs.