Faculty Bibliography

Antiepileptic drug (AED) guidelines are developed to improve medical decision making, to provide guidance and recommendation for patient management, to develop standards to judge or assess clinical practice, and to keep the cost-benefit ratio at an acceptable level. These guidelines are derived from evidence-based medicine (EBM), a four-tiered grading system that is used to analyze clinical trials and published experiments independent of clinical bias and experience. Although guidelines may not answer all questions it is critical that clinicians using them consider the available evidence, as well as the quality of the evidence, when incorporating the information in their decision making

BACKGROUND: Despite the success of several new antiepileptic drugs, about one third of patients with epilepsy are not seizure free on medication. Improvement in this situation might lie in drugs that are currently in development. RECENT DEVELOPMENTS: Some new antiepileptic drugs are modifications of those already available, referred to in this Rapid Review as evolutionary drugs. These modifications of existing drugs are developed to improve effectiveness, often by increasing tolerability. Other drugs work by new mechanisms and are usually discovered through screening of animal models. WHERE NEXT? The large number of drugs currently in clinical trials provides a measure of hope for patients whose epilepsy is not controlled with currently available medication. In the future, this range of antiepileptic drugs will probably increase because of the use of new animal models, discovery of new basic mechanisms of epileptogenesis, acceleration of proof of principle studies in people, and development of new methods of drug delivery

A unifying definition of refractory epilepsy has been hotly debated but, to date, has not been agreed upon. Evidence from clinical trials indicates that some patients actually are not refractory, as many will partially respond to add-on treatment or will worsen when antiepileptic drugs (AEDs) are removed. There are several important issues relating to the assessment of AED response that routinely have not been addressed in the determination of treatment responsiveness, such as incorporating baseline seizure severity, including partial response rather than solely an all-or-none response, and the consideration of variability in response over time

PURPOSE: To investigate whether rapid achievement of levetiracetam (LEV) steady state is translated into an immediate measurable efficacy. The time to onset of action of LEV immediately after its initiation in adult patients with refractory partial seizures was analyzed. METHODS: Treatment effect was assessed in a pooled analysis (n=883) from three randomized, double-blind, placebo-controlled add-on trials. RESULTS: The increase in the proportion of seizure-free patients over baseline was 15, 17, and 17% for the first, second, and third day, respectively, for the LEV 1,000-mg group (all differences statistically significant; McNemar p value<0.001), whereas the increase was 7, 9, and 9% for the 333-mg LEV group (differences not significant). No major changes were observed for the placebo group. For differences in proportion of seizure-free patients between groups, the probability of being seizure free in the LEV groups was twofold higher than in the placebo group. For the 1,000-mg LEV group, odds ratios were 2.3, 2.5, and 2.7 for the first, second, and third day of therapy, respectively; all differences versus placebo were statistically significant (logistic regression p values, all <0.001). The addition of LEV significantly increased the proportion of patients without a seizure as of the first day of therapy. Each of the first 3 days, seizure freedom was twice as likely to occur with LEV 1,000 mg than with placebo. CONCLUSIONS: Evidence of a rapid onset of action of LEV 1,000 mg was demonstrated through a significant increase in the proportion of seizure-free patients as of the first day of therapy