Epilepsy Armamentarium Continues to Grow
LAS VEGAS—Several newer antiepileptic drugs (AEDs) are, along with new surgical options and nontraditional interventions such as medical marijuana, among a growing number of epilepsy treatments offering the potential for increased efficacy and improved patient care. However, subpopulations such as pregnant women pose special challenges for treatment selection, and the large number of patients who remain refractory to any epilepsy therapy represents perhaps the greatest challenge of all. Of the estimated three million people in the United States who have epilepsy, approximately one-third have uncontrolled seizures because no available treatment works for them, said Tracey A. Milligan, MD, at the American Academy of Neurology’s Fall 2016 Conference. Dr. Milligan is Vice Chair for Education in the Department of Neurology at Brigham and Women’s Hospital and Assistant Professor of Neurology at Harvard Medical School in Boston.
Illustrating the challenges of trying to achieve more widespread seizure control, Dr. Milligan cited a study of new-onset epilepsy by Brodie and colleagues, who found that 37% of patients had their seizures initially controlled, 22% had them eventually controlled, 16% had fluctuating control, and 25% had seizures that were refractory to treatment. This breakdown resonated with Dr. Milligan in terms of what she sees in her own practice—starting with the patients whose seizures are initially controlled. “They start a medication, they do well, they go on to live very full, active lives,” she said. “For the other 22%, we need to spend a little more time adjusting medications. Maybe they are adjusting lifestyle factors, but they do get to full control as well.”
Patients in the refractory group should be referred to epilepsy treatment centers, where surgical options can be considered. It is patients with fluctuating seizure control whom Dr. Milligan finds particularly interesting. “This is our sort of ‘relapsing-remitting’ epilepsy,” she said. “You start an agent, you think you have the seizures under control, and the drug works for a little while. Then the patient starts having seizures again…. These patients also need to be referred to an epilepsy treatment center to … be worked up and think about surgery if it is drug-resistant epilepsy.”
Questions for AED Selection
Clinical decisions such as the choice of an AED should be informed by the latest guidelines. Citing a 2015 report on unprovoked first seizures in adults, Dr. Milligan said that after one unprovoked seizure, there is a 21% to 45% risk of another seizure in two years. In her view, this new guideline raises more questions than it provides answers—like the new International League Against Epilepsy definition of epilepsy, in which one unprovoked seizure (rather than the previously required two) can be enough to support a diagnosis of epilepsy.
“How do we know which [patients] to diagnose with epilepsy after a single seizure?” she asked. “How do we know which patients are at highest risk of having a second seizure and we’re going to start with an AED?.... At this point we do not have an agreed-upon and reliable formula where we can plug in the demographics and the factors of the seizure and calculate the risk.”
In lieu of such information, clinicians need to ask several questions when selecting an AED, including which epilepsy syndrome the patient has, which medicines work best with it, and which patient factors apply. Dr. Milligan discussed four newer AEDS that are clinically available—clobazam, perampanel, eslicarbazepine, and brivaracetam. “These, for the most part, have been in trials involving patients with refractory seizures and all have a similar efficacy as add-on therapy.”
Onfi (Clobazam)
A benzodiazepine that offers fewer tolerance/sedation issues than others in its class, clobazam has been used since the 1970s as an anxiolytic/anticonvulsant. In 2011, Onfi (clobazam) was approved by the FDA for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients age 2 and older. Adverse effects include dizziness, somnolence, restlessness, and aggression. “It is a nice option when you are thinking about a benzodiazepine, because it does not have the same sort of tolerance/dependence [issues] as the other benzodiazepines do with epilepsy,” said Dr. Milligan.
Fycompa (Perampanel)
Fycompa (perampanel) is a noncompetitive AMPA-receptor inhibitor with a long half-life (70 to 100 hours). It is indicated for adjunctive treatment of focal epilepsy and primary generalized tonic-clonic seizures in patients age 12 and older. Side effects include dizziness, somnolence, and rash. The drug’s labeling includes a black-box warning for an occurrence Dr. Milligan described as unusual but important to be aware of: “Very interesting conversations you have with your patients when you prescribe this—where you have to say, ‘You may develop homicidal ideation on this medication. If you start to feel like killing somebody, please let me know right away.’”
