NOV-DEC 2015 ISSUE

Update in Epilepsy Therapeutics

In addition to comorbid conditions and side effects, cost and availability should factor into therapeutic selection.
Update in Epilepsy Therapeutics
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The epilepsy therapeutic front is rapidly expanding, including new surgical modalities, new devices, as well as emerging strategies for acute management of seizures. At this year’s American Academy of Neurology Fall Conference in Las Vegas in October, Joseph Sirven, MD, gave an update on the newest developments in research and care.

Risk and Treatment. The most impactful psychosocial consequence of seizures, according to patients, is concern over driving, more so than employment and stigma, Dr. Sirven observed. Discussing the issue of who to treat and who not to treat, he said, “Almost no kids should be treated after a first seizure.” In this group, risk of recurrence is between 40 and 50 percent within two years. The recurrence risk in adults is between 30 percent and 60 percent, but Dr. Sirven noted that treatment might be warranted in adults based on certain factors. “Consider those with a hazardous occupation and not those with a clear precipitating factor,” he explained. Dr. Sirven further noted that those who definitely should be treated after a first seizure include patients with structural lesions, abnormal EEG, a history of previous symptomatic seizures, a history of previous brain injury, and status epilepticus at onset. On the other side of the spectrum, Dr. Sirven noted that individuals who should not be treated after a first seizure include those with alcohol withdrawal, drug abuse, acute illness, post-impact seizure, specific benign epilepsy syndrome, and seizure with excessive sleep deprivation.

Among patients who have had two or more seizures, the rate of recurrence is between 80 percent and 90 percent, so Dr. Sirven says, “All patients should be treated at this point.” Those with two or more seizures who should be treated are children with Benign Rolandic epilepsy and those who had either simple partial seizures or widely spaced seizures.

Choosing a Medication. According to Dr. Sirven, appropriate medication selection should be based on a variety of factors. After confirming diagnosis and seizure type, it is important to consider the mechanism of action of each agent, comorbid conditions and side effects, and also the speed of introduction. Comorbid conditions include bipolar disorder, migraine, neuropathy/neuropathic pain, trigeminal neuralgia, and tremor. In addition to the impact of AEDs on mood, other factors such as cost, availability, and potential for compliance should also factor in the decision, Dr. Sirven noted.

Dr. Sirven also described the importance of matching the seizure type to the ideal drug. While primary care and emergency physicians tend to favor drugs that offer broader coverage, the narrow spectrum encompasses a number of niche-oriented drugs offering individualized benfits, he observed. Narrowing the selection to one agent is often based on anecdotal evidence, as there are few comparative trials among AEDs. Nevertheless, despite inherent limitations of selecting the definitive agent, physicians should weigh all factors before making a selection, particularly given the importance that AEDs may play within overall care.

For more coverage of the latest developments in epilepsy, see Practical Neurology® magazine’s video updates from the recent American Epilepsy Society (AES) Annual Meeting, available at www.practicalneurology.com.n

Sizing Up the Newer Generation of AEDs

The three newest AEDs on the market are ezogabine (Potiga, GlaxoSmithKline), lacosamide (Vimpat, UCB), and perampanel (Fycompa, Eisai). Ezogabine is a potassium channel modulator indicated for partial epilepsy. Its side effects include urinary retention, neuropsychiatric symptoms, dizziness and sleepiness, mild changes in heart rhythm, suicidal thoughts, and blue skin discoloration. By contrast, lacosamide acts on long acting sodium channels. It is also indicated for partial epilepsy. Side effects of lacosamide include dizziness, nausea, diplopia, vertigo, mood changes, and PR prolongation. Finally, perampanel is also indicated for partial epilepsy and has recently been expanded to PGE. Side effects include dizziness, somnolence, nausea, imbalance, vertigo, weight gain, anxiety, irritability. Suicidal ideation can also be a risk in some patients on a higher dose. Dr. Sirven recommended assessing for mood very carefully and using lower doses to lessen this risk.

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