Abstracts

Keppra (levetiracetam) is an antiepileptic drug used as add-on-therapy for partial onset seizures in adults since its approval by the US Food and Drug Administration (FDA) in November of 1999. The exact mechanism(s) by which Keppra exerts its antiepileptic effect is unknown.
Since its approval by the FDA, several reports have shown an incidence of behavioral abnormalities, most notable being irritability and anger, following its use. This incidence ranged from 3.9% to 30%. This information is noted in the FDA prescribing information at a rate of 13.3% versus 66.2% for placebo. A retrospective analysis of medical records identified 57 adults treated with Keppra since November 2002. 31 were males and 26 were females. Five males reported behavior changes including depression, agitation, crankiness and suicidal ideation[apos]s which were significant enough to warrant discontinuation of the drug. One female reported a behavior change of increased irritation resulting in discontinuation of the drug. The 5 males represent 8.77% of all cases and 16.13% of all male cases. The female represents 1.75% of all cases and 3.85% of all female cases. From previous trials, we know the range of positive responses has been 3.9% to 30.0%. We assume this to be normally distributed and to cover 95% of the outcomes (2 standard deviations). We use the average of that (mu=16.95%) as the expected positive response for a group. Males were right near the average of previous studies. Females, in this study, were near 2 standard deviations away from the average. The incidents of males positive responses vs negative responses was right near the expected outcome. Therefore, from this particular study, being a male seems to be a factor that has no impact on one[apos]s reaction to the drug. The incidents of female positive responses vs negative responses was near 2 standard deviations from the average. Therefore, in this particular study, being a female is on the low end of the distribution, leading one towards believing that this factor might be important.
In this study, we saw males behave like the average and females behave quite a bit away from the average. However, many more studies must be done, and have similar outcomes, to validate these outcomes. (Supported by Aurora HealthCare.)