Faculty Bibliography

This review discusses the safety and tolerability of levetiracetam, as presented by the available literature, with attention paid to special populations. In Phase II/III trials, the adverse effects occurring more commonly in the treatment groups versus the placebo group were; somnolence (14.8 versus 8.4%), asthenia (14.7 versus 9.1%), infection (primarily common cold) (13.4 versus 7.5%), and dizziness (8.8 versus 4.1%). Adverse events usually appear within the first month after treatment initiation, are not dose-dependent, are mostly mild-to-moderate, generally resolve without medication withdrawal, and are transient when the medication is stopped. No significant changes in haematology and chemistry profiles or weight occurred. Hypersensitivity reactions were rare and no idiosyncratic event has been reported. Open-label studies have added patient data with other epileptic syndromes and from a wider patient pool, such as children and patients with prior psychiatric history. These studies have supported initial safety findings, but have reported increased behavioural adverse events in children and patients with a history of prior behavioural problems. Levetiracetam is proving to be safe and well-tolerated. So far, it appears to have a favourable safety profile in special populations, such as children, the elderly, and patients with hepatic dysfunction. Preliminary data in pregnancy are promising, but more data are needed on the impact of levetiracetam on the developing fetus and pharmacokinetic alterations caused in pregnancy. Adjustments in dosing are required for decreases in renal clearance

The current evidence-based data on efficacy, safety, and administration of the 7 new antiepileptic drugs (AEDs) approved over the past 10 years by the US Food and Drug Administration to treat new-onset and refractory epilepsy in children and adults is summarized based on the recent American Academy of Neurology (AAN) guidelines. The clinical trial work still necessary as well as areas where such research would not be informative and those in which nonevidence-based strategies are needed are highlighted in efforts to provide clinicians with the most up-to-date information on treatment regimens for patients with epilepsy. The limited amount of data currently available on these newer AEDs and the existence of traditionally efficacious medications complicate therapeutic decision-making for the clinician. Neurologists are encouraged to integrate the AAN guidelines with clinical experience, opinion, and other considerations of special populations until an exhaustive set of guidelines is available for a wide variety of seizure types

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide-reviewed in the order in which these agents received approval by the US Food and Drug Administration) in the treatment of children and adults with newly diagnosed partial and generalized epilepsies. METHODS: A 23-member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until September 2002, with selected manual searches up until 2003. RESULTS: There is evidence either from comparative or dose-controlled trials that gabapentin, lamotrigine, topiramate, and oxcarbazepine have efficacy as monotherapy in newly diagnosed adolescents and adults with either partial or mixed seizure disorders. There is also evidence that lamotrigine is effective for newly diagnosed absence seizures in children. Evidence for effectiveness of the new AEDs in newly diagnosed patients with other generalized epilepsy syndromes is lacking. CONCLUSIONS: The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with newly diagnosed epilepsy and identify those seizure types and syndromes where more evidence is necessary

OBJECTIVE: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) (gabapentin, lamotrigine, topiramate, tiagabine, oxcarbazepine, levetiracetam, and zonisamide) in the treatment of children and adults with refractory partial and generalized epilepsies. METHODS: A 23-member committee including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane library for relevant articles from 1987 until March 2003. RESULTS: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. Gabapentin can be effective for the treatment of mixed seizure disorders, and gabapentin, lamotrigine, oxcarbazepine, and topiramate for the treatment of refractory partial seizures in children. Limited evidence suggests that lamotrigine and topiramate are also effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox Gastaut syndrome. CONCLUSIONS: The choice of AED depends upon seizure and/or syndrome type, patient age, concomitant medications, AED tolerability, safety, and efficacy. The results of this evidence-based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes where more evidence is necessary