Epilepsy

Abstract

Approximately 30% of patients with epilepsy are medically refractory despite multiple antiepileptic drug (AED) trials due to continued seizures or intolerable side effects. Novel AEDs and other therapies are needed that are more effective with improved tolerability. New treatments and new insights into management of comorbidities are discussed, with a focus on adult patients with epilepsy. The Food and Drug Administration (FDA) recently approved 3 new AEDs, and a fourth AED may be near approval. Lacosamide (LCS) is approved by the FDA for adjunctive treatment for partial-onset seizures. It has novel mechanisms of action, enhancing the slow inactivation of voltage-gated sodium channels and binding collapsing response mediator protein 2. LCS has a low potential for drug–drug interactions, is renally excreted, and is dosed twice daily. It does not affect plasma concentrations of concomitant AEDs. The most common adverse effects were dizziness, headache, diplopia, nausea, and vomiting, which were mild or moderate. Small increases in the PR interval were observed, but were not of clinical consequence. In a recent randomized, double-blinded, placebo-controlled trial of adjunctive treatment with LCS for medically refractory partial-onset seizures at doses of 400 to 600 mg daily, median reductions in seizure frequency were 37.3% for the 400 mg/day and 37.8% for the 600 mg/day groups. For secondarily generalized tonic-clonic seizures, median reductions in seizure frequency were more robust at 59.4% for the 400 mg/day group and 93.0% for the 600 mg/day groups. In addition, 8% of the patients in the 600 mg/day group became seizure-free.1 Rufinamide (RUF) is FDA-approved for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS). This new AED adds to the AEDs already used for LGS including valproic acid, lamotrigine, felbamate, and topiramate. Its mechanism of action includes limiting the excessive firing of sodium-dependent action potentials, but RUF also exhibits a broad …