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Sudden Unexpected Death in Epilepsy (SUDEP)
It’s a little known fact that sudden unexpected death in epilepsy (SUDEP) accounts for approximately 18% of all deaths among people with epilepsy. Drs. Ted Walczak and Ilo Leppik of MINCEP were lead authors for an article on SUDEP in Neurology, the Journal of the American Academy of Neurology. The abstract can be found here.
The article, based on a five year study run out of MINCEP Epilepsy Care, is significant in that it determines a profile of the person with epilepsy most at risk of dying. Of the patients in the study, those who had tonic-clonic seizures, particularly if they took more than two antiepileptic medications, and those who had a Full Scale IQ of less than 70 were most at risk. The number of tonic-clonic seizures the patient experienced was a risk factor for women, but the data was not clear for men. This is expected to be clarified as more patients are studied for a longer period of time.
MINCEP® Medical Alert: Don't Mix These Herbs!
There is evidence that using certain herbal supplements may lower a person's seizure threshold. In fact, active compounds found in some herbal products and dietary supplements, used in combination with antiepileptic medications, may actually induce seizures in some people. If you are in doubt, don't use them. Consult your physician.
HERB SEIZURE POTENTIAL
Black Cohash: 1 seizure case reported
Borage: Contains gamolenic acid, may lower seizure threshold
Cranberry: Currently no known seizure potential
Damiana: Lowers seizure threshold
Echinacea: Currently no known seizure potential
Evening Primrose oil: Contains gamolenic acid, may lower seizure threshold
Garlic: Currently no known seizure potential
Ginkgo Biloba Seeds: Dried & fresh leaves extract produced MAO inhibition in rats. Tonic/clonic seizures reported. May lower seizure threshold.
Ginseng: May lower seizure threshold
Goldenseal: Contains hydrastine, may lower seizure threshold
Green Tea: contains 1%-4% (10-50 mg/180ml) of caffeine. May lower seizure threshold if more than 3 cups/day.
Guarana: Contains caffeine & theophylline, may lower seizure threshold.
Herbal Phen-Fen: Contains MaHuang, lowers seizure threshold, contains Ephedrine.
Kava Kava: Generalized tonic/clonic seizures reported both from toxicity and acute withdrawal.
MaHuang: Contains ephedrine and pseudoephedrine; seizures reported
St. John's Wart: Seizures reported
Metabolife: 356 Seizures reported
Felbatol: Warning Removed
Felbatol is a very powerful antiepileptic medicine used to treat a broad variety of seizure and seizure syndrome types. Historically, it has been a difficult medicine for physicians to prescribe because it interacts with a great many other medicines, including other antiepileptic medications. Determining proper dosing can also be difficult. Shortly after Felbatol was introduced to market, a few of those who use it developed severe blood dyscrasias and died unexpectedly. The Food and Drug Administration (FDA) issued a warning and required that the medication be used only for very difficult-to-control patients. They suggested further testing.
As more data has been gathered, the FDA has withdrawn the warning and Felbatol is now approved for more ordinary use. The problem was not as serious as first thought. If patients have not had severe reactions to other drugs, they are not likely to have a severe reaction to Felbatol.
Nonetheless, it is a difficult drug to use well. Patients whose seizures have not responded to other medicines might well react favorably to Felbatol, but it is recommended that they be in the hands of a physician who is familiar with the medicine.
Newer Antiepileptic Drugs
Fycompa® (perampanel) Drug Interactions
Enzyme inducing drugs like carbamazepine, oxcarbazepine, phenytoin, and primidone can decrease Fycompa plasma levels significantly and so decrease Fycompa’s effectiveness.
Fycompa decreased the plasma levels of the oral contraceptive leovorgestrol by 40% increasing possibility of pregnancy. This information indicates that oral contraceptives may lose their efficacy after Fycompa is started. Women using Fycompa and oral contraceptives should consult with their gynecologist about potential oral contraceptive failure and birth control choices.
Fycompa up to 12 mg/day did not significantly change carbamazepine, levetiracetam, Phenobarbital, phenytoin, topiramate, or zonisamide levels. Fycompa had some effect on carbamazepine, onfi, lamotrigine and depakote levels though it is not clear whether this will be important in all patients. Fycompa moderately increases oxcarbazepine levels but this interaction is not fully understood.
In general Fycompa is not a first line antiseizure medication. It should be used by physicians who are experienced in the treatment of seizures and familiar with possible interactions with other medications.
Potiga™(ezogabin) is also known internationally as retigabine. It was developed jointly by Valeant Pharmaceuticals and GlaxoSmithKline. The FDA approved Potiga in June of 2011 as an adjunctive treatment for partial onset seizures in patients age 18 and older. Since May of 2012 it has been available in US pharmacies. It is a controlled substance (CV) due to potential abuse and may lead to drug dependence. Before Potiga is started, your physician will need to obtain prior approval from most insurance companies.
It is different from all currently approved anti-epileptic drugs. Its primary mechanism of action is as a neuronal potassium (K+) channel opener. It appears to be acting on neuronal potassium channels to keep them in an open position, thus reducing excitability.
In common with other anti-epileptic drugs, the FDA warns about suicidal thoughts. Potiga seems to have a particular effect on bladder activity and may make it difficult to empty your bladder. It also has interactions with other medications.
Vimpat®(lacosamide) is marketed by UCB Pharma. It is one of the newer AEDs on the market. It was approved by the FDA as an add-on medication for simple partial and complex partial seizures. Its precise mechanism of action is not known. It is not metabolized in the liver by the cytochrome P450 system and therefore lacks drug-drug interaction. Vimpat is available in tablet form and solution for daily use. When needed, it can be given intravenously. Its role is as a safe, effective antiepileptic drug which can be added on relatively fast to other AEDs without concern of drug interactions.
Banzel®(rufinamide), manufactured by Eisai, is also a relatively new drug indicated for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in children 4 years and older and adults. Banzel is metabolized in the liver (not by the cytochrome P450 system) and has interactions with other medications. Also, oral contraception will be rendered less effective, and the addition of non-hormonal forms of contraception is recommended when Banzel is used.
Onfi®(clobazam), a relatively long-acting benzodiazepine, has been available in Europe since 1975. It was first approved as an anti-anxiety drug, and then in 1984 as an anti-seizure medication. In October of 2011, it was approved in the United States for the treatment of seizures associated with Lennox-Gastaut syndrome in patients two years of age and older. The dose depends on the patient’s weight and it is usually given two times per day. Onfi has significant drug interactions. Therefore it is important that the physician knows all medications a patient is taking. Patients are not to drink alcohol while using Onfi. Before Onfi can be started, the physician will need to obtain prior approval from most insurance companies.
Suicide and Antiepileptic Drugs: Is There Cause for Alarm? Is There Potential Harm?
(Prevalence of Depression in the Epilepsy Population)
MINNEAPOLIS, February 4, 2008 - The Federal Drug Administration (FDA) just released an alert, reporting increased suicidal behavior or thinking among patients treated with antiepileptic drugs (AEDs). Patients taking AEDs should not be alarmed. Patients should not risk seizures by ceasing to take medication. If patients have any concerns, they should visit a physician knowledgeable about the use of antiepileptic medicine. Patients with a general diagnosis of epilepsy should have as precise a diagnosis as possible so use of medication is as appropriate as possible.
Time will tell whether the concerns raised by the FDA alert are real or not. In the meantime we must deploy sound clinical judgment and careful communication with our patients to counteract the half-information. We will continue to address the data as it becomes available. The FDA finding may be coincidental or even be a sampling problem.
The prevalence of depression is higher in people with medically refractory epilepsy than in the general population. Recent population based studies, including one performed at MINCEP Epilepsy Care, demonstrate that depression is more common in people with less severe epilepsy than in the general community.
Recent work has demonstrated fairly conclusively that depression is a risk factor for epilepsy. In other words, according to epileptologists at MINCEP, depression is more common in people who develop epilepsy than in people who do not. Both psychiatric disorders and psychiatric reactions to medications are higher in people with brain injury, who also are at higher risk for the development of seizures.
There is a danger that the factors that increase risk for depression in epilepsy, will be ignored by patients or by physicians and that both depression and suicidal thought will be blamed on the antiepileptic drugs. Patients should not stop taking antiepileptic drugs or resist treatment when it is necessary.
MINCEP epileptologists recommend the following:
- Patients with new and established epilepsy should be screened for depression
- Clinicians need to consider avoiding medications more likely to cause depression in such patients.
- Perhaps most importantly, patients need to learn about their own type of epilepsy and its potential acute and long-term impact. Lack of information exacerbates the anxiety associated with the initial diagnosis and augments any underlying depressive tendencies.
- Patients and their physicians need to discuss the possibility of a worsening depression and clarify parameters that would require further intervention.
- Patients need to understand the dangers of sudden discontinuation of antiepileptic medication.
- Physicians need to provide realistic information regarding prognosis, which is usually much better than most patients suspect and direct patients to appropriate resources to help ameliorate any adjustment reaction.
- These suggestions are not anything new. They are basic features of a comprehensive patient-centered approach which we have long advocated at MINCEP Epilepsy Care.