“Clinical use of ezogabine has been limited by the pigmentation and by tid dosing, which patients do not like,” Dr. Bazil said. Although the bluish color resolves over time, patients are likely to discontinue this Schedule V drug, which also is associated with dizziness and somnolence, before this occurs.
Eslicarbazepine, an Unscheduled Agent
Eslicarbazepine, a sodium channel blocker, has been approved as adjunctive and monotherapy for partial epilepsy. Although monotherapy trials with a placebo control are no longer considered ethical in patients with epilepsy, eslicarbazepine and lacosamide have been evaluated and found effective in trials in which other active agents were withdrawn over time to allow response on monotherapy to be monitored, Dr. Bazil explained.
Eslicarbazepine is also distinguished from other newer agents by the fact that it is not a scheduled agent. It is primarily metabolized by the liver and has a half-life of 13 to 20 hours. Due to its structural similarity to carbamazepine and oxcarbazepine, these agents should not be combined, said Dr. Bazil. Eslicarbazepine, like clobazam, also could interfere with the bioavailability of oral contraceptives.
“Eslicarbazepine is essentially a longer-acting carbamazepine, a drug with which we are all familiar,” said Dr. Bazil. Although eslicarbazepine also may cause the dizziness, somnolence, and nausea common to carbamazepine, its longer half-life has the potential to diminish peak effects to improve tolerability.
New and Emerging Therapies
Brivaracetam, which was approved for add-on therapy of refractory partial seizures for patients age 16 or older, “is structurally and functionally related to levetiracetam, but approximately 20 times more potent at the SV2A receptor,” said Dr. Bazil. As this recently approved drug is not yet widely used, its relative clinical utility within the context of other choices is not well established, but the side effects common to AEDs, such as dizziness and somnolence, have been relatively mild on this agent in the clinical trials.
Of treatment strategies on the horizon, Dr. Bazil drew attention to SAGE-547, an experimental agent now in a phase III study that has demonstrated uncommon efficacy for refractory status epilepticus, a condition for which there is a large unmet need for reliably effective treatments. In addition, researchers are conducting ongoing efforts to individualize therapy by identifying targetable underlying genetic mutations responsible for seizure activity.
Overall, the therapies approved during the past 10 years have expanded choice in a way that may increase the likelihood of providing a patient with adequate efficacy and acceptable tolerability. Although newer pharmacologic options have not yet generated a major leap in seizure control, coming therapies or strategies to better match existing therapies to the underlying seizure mechanism may yield greater rates of seizure freedom, said Dr. Bazil.
—Ted Bosworth
