Epilepsy Therapy Update: A Whirlwind Review


Quick, how many of the following-eslicarbazepine, ezogabine, parampanel-do you recognize? These new entries into the medical armamentarium were highlighted at the AAN 2015 Annual Meeting.



One of my favorite meetings to attend is the American Academy of Neurology’s Annual Meeting. It is a great way to gather information on all topics in neurology. Every time I register for this event, I feel like a child gaining entrance into an amusement park. Every ride seems thrilling, but time, cost, and my schedule force me to limit my choices.

This year, one of the first courses I attended was on epilepsy therapy, presented by Dr Erik St Louis from the Mayo Clinic in Rochester, MN.

Dr St Louis’s course on epilepsy therapy was a great way to receive updated information. There are alternative methods to get this information, however. For instance, I could meet with 10 to 15 pharmaceutical representatives, but that would be inefficient. It would also prove dangerous to my health-unless I provided my own healthy lunch or dinner. I’d also have to consider the inherent biases in using them as my only source of medical information.

Another possibility is reading in multiple journals about each of the medications. Or, I could wait for the triennial “Continuum” Epilepsy update. Although I don’t like being “spoon-fed” my information, there is something about a combination of visual and aural information that works well for me.

Quick, how many of the following-eslicarbazepine, ezogabine, parampanel-do you recognize? Is this a list of the most recent cancer-causing food preservatives? No, these are just the latest 3 entries into the medical armamentarium available to neurologists treating epilepsy.

Dr St Louis gave thumbnail introductions to the medications. If you have seen the Blue Man Group, then you would recognize what I say when the “blue person syndrome” has been seen with ezogabine. Up to 6% of study patients taking this medication developed a bluish hue to their lips, fingernail beds, and sometimes even their retinas. Dr St Louis mentioned that this drug is considered “dead on arrival” similar to vigabatrin and felbamate due to this nontrivial side effect and like those 2 medications is reserved for intractable epilepsy cases.

Eslicarbazepine appears to be a useful and safe medication. Parampanel, although useful, carries a blackbox warning from the FDA due to possible neuropsychiatric adverse events, including aggression, hostility, irritability, and even homicidal thoughts. Unfortunately, there were no characteristics that pointed out which patient may have these significant adverse events.

I was hoping to get a cheat-sheet on the new-generation antiepileptic drugs (AEDs) that could help me get through the maze of these medications or at least help me find my new “best” medication for seizures. Eslicarbazepine only partially fits the bill. However, the information Dr St Louis provided helped me draw an “internal map” of how to use these medications.

Following the KISS (“keep it simple, stupid”) method, here is my “internal map” to the current use of AEDs in epilepsy:

• Most all AEDs are similar in efficacy.

• Initial treatment should be based on the seizure syndrome; if unknown, then seizure type.

• If seizures are mixed or generalized, consider lamotrigine, levetiracetam, topiramate, zonisamide, clobazam, or valproic acid. But with valproic acid, keep in mind its adverse effects on the unborn child in women who are of childbearing age and not using effective contraceptive therapy.

• If seizures are focal, consider eslicarbazepine, oxcarbazepine, gabapentin, carbamazepine, or phenytoin.

• The newer drugs are better tolerated.

• Save the “old drugs” for refractory cases.

• If refractory epilepsy, refer out.

• Don’t forget quality of life (QOL) for your patient.

These last 2 were emphasized in the latter half of Dr St Louis’s presentation: first, regarding the diagnosis and referral of refractory epilepsy; and second, covering the often-ignored interictal state.

The diagnosis of refractory epilepsy has undergone an evolution. For a long time, it was considered one of those items that “you’d know it when you see it.” In 2014, the AAN updated its Epilepsy Quality Measures and added “referral of treatment-resistant epilepsy to comprehensive epilepsy center every 2 years.”

Dr St Louis clarified that intractable epilepsy is now considered to be the failure of 2 AEDs (alone or in combination) that have been adequately chosen, trialed, and tolerated. He pointed out the dismal odds of getting seizure freedom after failing 2 AEDs as being as low as 4% to 5%.

A conference attendee asked whether Dr St Louis believed this statement, to which he answered “yes,” with caveats: Having intractable epilepsy does not mean you don’t keep trying other medications, it should act as a prompt to the neurologist to refer the patient to a comprehensive epilepsy center and it should also open the neurologist’s and patient’s options to nonpharmacological treatment, such as diet changes and nerve stimulators.

Dr St Louis also covered the interictal state, or the time period in between seizures, and measures of QOL for patients with epilepsy. Patients who have poorly controlled seizures consider their QOL as worse than do patients with most other neurological diseases. The predictor of QOL was the effect on cognition and coordination. Of utmost importance was avoiding adverse effects with medications by personalizing both the medication and the dose titration schedule based on the patient’s characteristics, comorbid conditions, and co-medications.

Dr St Louis’s talk touched on multiple other topics that would make this blog piece seem like a book. They included:

• An update on the definition of epilepsy.

• Epilepsy as a “network problem” rather than being only anatomic in nature.

• Drug pharmacotherapy and interactions as being absent, unidirectional (only the AED is affected), or bidirectional (both the AED and other co-medications are affected).

• Observational studies on autoimmune epilepsy and its treatment with steroids or immunoglobulins.

• Daytime sleepiness in patients with epilepsy and the significance of looking for obstructive sleep apnea and restless legs syndrome.

• And even when to consider discussing with the patient the sudden unexplained death in epilepsy syndrome, especially as you consider a patient with intractable epilepsy.

In the end, this was a true whirlwind review of the current status of therapy in epilepsy.

The AAN 2015 Annual Meeting is taking place April 18-25 in Washington, DC.

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