Epilepsy Armamentarium Continues to Grow
Aptiom (Eslicarbazepine)
Approved by the FDA in 2013 for partial epilepsy (monotherapy or adjunctive treatment), Aptiom (eslicarbazepine) is a sodium-channel blocker whose longer half-life (20 hours) may help with peak effects and reduce hyponatremia and rash. It has few drug interactions and can be used with carbamazepine, though not with oxcarbazepine. Although the list of its most common side effects is long—dizziness, somnolence, nausea, headache, diplopia, vomiting, fatigue, vertigo, ataxia, blurred vision, and tremor—it “probably has fewer adverse effects associated with it [overall] than other AEDs do.”
Briviact (Brivaracetam)
The newest agent, Briviact (brivaracetam), was approved in February 2016 as add-on therapy for refractory partial seizures in patients age 16 and older. Clinical trial results showed adverse effects such as somnolence, headache, dizziness, and fatigue to be mild and similar to what control patients experienced on placebo, but with a higher incidence of psychiatric/cognitive problems versus placebo. It is 20 times more potent at the SV2A receptor than levetiracetam, a related agent. “Unlike levetiracetam, it does [affect] oral contraceptives at a higher dose,” said Dr. Milligan, adding that she is inclined to use it after she has “tried tried agents that have been around longer”—at least until more data are in.
Marijuana, Pregnancy, and Depression
Dr. Milligan devoted the rest of her lecture to pregnancy, depression, and “the thing that everybody asks us about”—marijuana. She cited an open-label interventional trial by Devinsky and colleagues that found that cannabidiol might reduce seizure frequency and have an adequate safety profile in children and young adults with highly treatment-resistant epilepsy. “We do not have many randomized placebo-controlled trials at this point,” she said. “[Cannabidiol] probably works well for some syndromes but it does have adverse effects.”
Regarding pregnancy, a study by MacDonald and colleagues that examined complications in women giving birth showed a 10-times higher risk of death in women with epilepsy, along with a greater rate of every complication the investigators assessed. Other risks are associated with AED therapy. “We know that there are risks of seizures during pregnancy, and these are important to control,” said Dr. Milligan. “There are also risks that come along with taking certain AEDs—neural tube defects, small for gestational age, cleft lip and palate, and autism.”
One drug associated with cleft lip/palate and small size for gestational age is topiramate (FDA pregnancy category D). “Being a baby with small for gestational age carries an increased risk of obesity, cardiovascular disease, diabetes, and cognition [problems]—so it is important for us to be aware of [this fact] when we use topiramate,” said Dr. Milligan, who also cited findings from the North American Pregnancy Registry showing lamotrigine and levetiracetam to be the safest among AEDs assessed.
Depression is present in more than 33% of patients with epilepsy and entails a three- to four-times greater risk of suicide. Sudden death is 27 times more likely in patients with epilepsy than in the general population. “Seizures kill—this is something people are not aware of,” Dr. Milligan emphasized. “Depression is very prevalent, but there is also this high risk of death that goes along with epilepsy that is not just sudden unexplained death in epilepsy [SUDEP] but accidental death, assault….
“Mortality risk and years of potential life lost from epilepsy are second only to stroke. We need to think about education. For example, most patients who are found dead after a presumed seizure or from SUDEP are in a prone position. Maybe we should have for those refractory patients [something] like the sudden infant death syndrome campaign for babies to sleep on their backs, and not prone. It’s something to think about.”
—Fred Balzac
Suggested Reading
Brodie MJ, Barry SJ, Bamagous GA, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology. 2012;78(20):1548-1554.
Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15(3):270-278.
Devinsky O, Spruill T, Thurman D, Friedman D. Recognizing and preventing epilepsy-related mortality: a call for action. Neurology. 2016;86(8):779-786.
Hernandez-Diaz S. Evidence accumulates on the association between topiramate use early in pregnancy and the risk of oral clefts. Pharmacoepidemiol Drug Saf. 2014;23(10):1026-1028.
Krumholz A, Shinnar S, French J, et al. Evidence-based guideline: management of an unprovoked first seizure in adults: Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;85(17):1526-1527.
Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010;51(6):1069-1077.
MacDonald SC, Bateman BT, McElrath TF, et al. Mortality and morbidity during delivery hospitalization among pregnant women with epilepsy in the United States. JAMA Neurol. 2015;72(9):981-988.
Martin RC, Faught E, Richman J, et al. Psychiatric and neurologic risk factors for incident cases of new-onset epilepsy in older adults: data from U.S. Medicare beneficiaries. Epilepsia. 2014;55(7):1120-1127.
Pennell PB. Use of antiepileptic drugs during pregnancy: evolving concepts. Neurotherapeutics. 2016;13(4):811-820.
Vajda FJ, O’Brien TJ, Lander CM, et al. The teratogenicity of the newer antiepileptic drugs - an update. Acta Neurol Scand. 2014;130(4):234-238.
