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Epilepsy in Adults: A Healthcare Professional's Guide

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Nov 2, 2020.

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Epilepsy: A Seizure Repeated

As a member of a primary healthcare provider team, you will most likely care for patients with epilepsy in your practice.

Epilepsy is a neurologic disorder that results in abnormal brain electrical activity and results in repeated seizures over time. Changes in attention or behavior, unconsciousness and convulsions may occur. A single seizure is not considered epilepsy.

How many people in the U.S. have epilepsy?

  • About 1.2% of the U.S. population has epilepsy based on the latest data, an it usually begins between the ages of 5 and 20 years old.
  • This equates to about 3.4 million people in the U.S. with epilepsy: 3 million adults and 470,000 children, according to the CDC.
  • However, seizures can begin at any age, and there may be a family history of seizures or epilepsy.

Treatment is important for a variety of reasons, but especially because seizures can lead to injury, especially when driving, swimming or during other activities.

Goals of Epilepsy Treatment

There are many options for treatment of epileptic seizure activity in adult patients. In fact, over 20 antiepileptic drug (AED) treatments are now approved.

Therapy should be individualized based on:

  • Seizure type
  • Frequency and severity of seizures
  • Possible side effects
  • Lifestyle considerations.

While roughly 50% of patients will respond to their AED treatment, overall up to 80% of patients can become seizure-free on medication.

The primary goals of treatment include:

  • Controlling seizures with a goal of seizure remission
  • Avoiding treatment adverse events
  • Improve and maintain quality of life
  • Educating and empowering the patient to take control of their disease

Seizure Types in Epilepsy

Identifying the seizure type is paramount to selecting the appropriate pharmacotherapy.

Seizures fall into two general categories: partial (focal) and generalized.

  • A partial-onset seizure only occurs in one specific part of the brain, such as a lobe or hemisphere, and may or may not be associated with an aura (pain, fear, unusual smells) or unconsciousness.
  • A generalized seizure occurs in both hemispheres of the brain with altered consciousness. Generalized seizures include tonic-clonic (grand mal), absence seizures (petit mal), and myoclonic seizures.

AEDs: When to Start, How to Choose

In an adult with newly diagnosed epilepsy, the type of seizure activity will help to guide the selection of drug treatment. AEDs are either broad spectrum or narrow spectrum agents.

  • Broad-spectrum drugs can be used to treat both partial onset and generalized seizures.
  • Narrow-spectrum agents are used to treat either broad-spectrum or narrow-spectrum seizures.

Immediate AED treatment at the time of the first unprovoked seizure is debated.

  • Some clinicians may start treatment immediately after a first seizure in high risk patients.
  • However, after two or more seizures not due to recognizable and treatable causes, AED treatment is usually started as the risk for a subsequent seizure is significant (57% by one year and 73% by four years).

AEDs may not need to be life-long therapy. Over 50% of children with epilepsy who do not have symptoms can eventually stop treatment and remain seizure-free. Adults who stop having seizures may also be able to discontinue medications after several years.

AED Categories: Broad-Spectrum

Lists of antiseizure medications:

Examples of broad spectrum drugs that can be used to treat both partial and generalized onset seizures include:

For detailed prescribing information, readers should refer to the individual drug information in Drugs.com.

AED Categories: Narrow-Spectrum

Lists of antiseizure medications:

Examples of narrow spectrum agents that are primarily used to treat partial-onset (focal) seizures or those that spread bilaterally include:

Ethosuximide (Zarontin) is also a narrow spectrum AED but is used only for absence seizures or "petit mal" seizures in adults and children.

In July 2019, the FDA granted the first generic approvals of pregabalin. It is used as adjunctive therapy for partial onset seizures in adults and children who are at least 1 month old (immediate release only). It is also used to treat neuropathic pain (diabetic neuropathy and post-herpetic neuralgia) with the immediate release and extended release forms, fibromyalgia (immediate release only) and spinal cord injury (immediate release only).

For additional detailed prescribing and dosing information, refer to the individual drug information monographs in Drugs.com.

Other Considerations in Selection of Initial AED

Monotherapy is preferentially used for initial treatment of epilepsy. Roughly 50% of patients will become seizure-free with their first drug used for monotherapy.

Comparative data among treatments are limited, and most trials do not show a significant difference in effectiveness for most agents.

Points to consider in selection of an AED include:

Benzodiazepines in Epilepsy

Benzodiazepines (BZDs) have long been used for the control of seizure activity in epilepsy. However, due to a build-up of tolerance, their use long-term in epilepsy is limited.

Benzodiazepines enhance responses to the inhibitory neurotransmitter GABA by opening GABA-activated chloride channels and allowing chloride ions to enter the neuron.

Clobazam (Onfi) is approved for use as an adjunct in Lennox-Gastaut Syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

In May 2019, the FDA approved midazolam nasal spray (Nayzilam) from UCB to treat patients with seizure clusters. Nayzilam is given as a single dose and is used in patients 12 years of age and older. Nayzilam is the first nasal spray option for treating seizure clusters.

In Jan. 2020, Valtoco (diazepam) nasal spray was approved for acute treatment of intermittent, stereotypic episodes of frequent seizure activity (i.e., seizure clusters, acute repetitive seizures) that are distinct from a patient’s usual seizure pattern in people with epilepsy 6 years of age and older. It is given by a caregiver in a ready-to-use formulation. The most common side effects with Valtoco (at least 4%) were somnolence, headache, and nasal discomfort.

Other BZDs used for seizures include clorazepate and lorazepam. Lorazepam or rectal diazepam are often used for status epilepticus.

Sudden withdrawal of BZDs can precipitate a seizure; discontinuation of this class in epilepsy patients should be tapered slowly.

Qudexy XR

For seizure activity, Qudexy XR (topiramate extended-release capsule) is indicated for:

  • Initial monotherapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures
  • Adjunctive therapy in patients 2 years of age and older with partial onset or primary generalized tonic-clonic seizures.
  • Adjunctive therapy in patients 2 years of age and older with seizures associated with Lennox-Gastaut syndrome.

Qudexy XR capsules can be swallowed by mouth OR opened and sprinkled onto a spoonful of soft food such as applesauce, which may be easier for small children to take. Swallow the mixture right away without chewing. Do not save it for later use.

See More: Qudexy XR dosing (in more detail)

Spritam (levetiracetam): Made with 3D Print Technology

Swallowing large tablets or capsules can be difficult for children. Spritam (levetiracetam) was approved in 2015 as the first drug made with 3D technology.

The new ZipDose Technology enables the delivery of a single high dose (up to 1,000 mg with a sip of liquid). Easier swallowing for patients may prevent episodes of breakthrough seizures.

Spritam is used as add-on therapy for adults and children with epilepsy as follows:

  • Partial onset seizures in patients with epilepsy 4 years of age and older weighing more than 20 kg.
  • Myoclonic seizures in patients 12 years of age and older with juvenile myoclonic epilepsy
  • Primary generalized tonic-clonic seizures in patients 6 years of age and older with idiopathic generalized epilepsy.

Levetiracetam is also available in generic and other brand names known as:

Aptiom and Briviact

Aptiom (eslicarbazepine) was first approved in 2013 as adjunctive therapy for partial-onset seizures. In September 2015, FDA also approved once-daily Aptiom tablets as monotherapy for the treatment of partial-onset seizures; it can be used as initial monotherapy or in patients who switch from another treatment. Aptiom is used in adults and children who are at least 4 years old. It is given as a once-daily therapy.

  • The most common treatment-related side effects with Aptiom include: headache, ataxia (lack of muscle coordination), blurred vision, dizziness, vertigo, fatigue, drowsiness, diplopa (double vision), somnolence, vertigo (spinning feeling), tremor, nausea and vomiting.

Briviact (brivaracetam) was first approved in 2016. Briviact is an analog of levetiracetam and the injection is used as monotherapy or as an add-on treatment for partial onset seizures in patients age 16 years and older when oral administration is temporarily not feasible. Briviact oral is for use in adults and children who are at least 4 years old.

  • In clinical trials, common side effects with Briviact included drowsiness, dizziness, fatigue, and nausea/vomiting. Briviact is classified as a schedule V controlled substance.
  • The clinical study experience with Briviact injection is limited to 4 consecutive days of treatment.

Side Effect Profiles of AEDs

Adverse effects can greatly affect adherence and quality of life in patients with epilepsy, therefore, these issues should be considered at treatment initiation.

Certain adverse effects, such as sedation, drowsiness, dizziness, diplopia (double vision), blurred vision or ataxia can occur with most AEDs.

Other important side effects to consider include:

  • cognition effects
  • hypersensitivity reactions like SJS, TEN or rash
  • increased risk of suicide
  • weight gain or weight loss
  • nausea
  • headache
  • teratogenic effects

Specific patient populations will need specific medication management to ensure safe outcomes, this includes:

  • women of child-bearing potential
  • elderly with renal or hepatic impairment
  • adults who depend upon driving will need specific medication management to ensure safe outcomes.

Use of AEDs in Women of Child-Bearing Age

Major risks of AED use in pregnancy include teratogenic effects of exposed infants and possible cognitive declines later in life in the child. However, seizures are also known to be detrimental to the fetus, so a risk-benefit assessment must be weighed.

According to data published in Up to Date, over 90% of women with epilepsy will have good outcomes. Women who take AEDs and wish to become pregnant should preplan and regularly consult with their specialist prior to and during pregnancy. The majority of women with epilepsy have a normal pregnancy; however, pre-planning is essential to a favorable outcome.

When possible, valproic acid should not be used in pregnant women, women who plan to become pregnant, or women of childbearing potential for the treatment of epilepsy or bipolar disorder due to adverse outcomes in the child. Alterantive agenst are preferred, when possible.

  • The rate of congenital malformations with valproate is about four times higher than other AEDs. Up to 4 in 10 babies are at risk of developmental disorders, and approximately 1 in 10 are at risk of birth defects.
  • This drug should not be discontinued abruptly as this can precipitate status epilepticus with resulting maternal and fetal hypoxia.
  • A recent 2020 study in Neurology also suggests that use of valproate can elevate the risk of having a child with autism, although a cause and effect was not proven.

Folate should be prescribed to all women of child-bearing age receiving AEDs both prior to conception and during pregnancy to lower the risk of neural tube defects. Higher doses of folate are required in women receiving valproate or carbamazepine.

Risk Factors for Epilepsy or Recurrent Seizures

While a single seizure may not warrant immediate AED treatment, patients with certain risk factors should be considered for treatment.

Risk factors for epilepsy or a subsequent epileptic seizure after an initial event include:

  • stroke
  • dementia
  • electroencephalogram (EEG) features
  • family history
  • brain tumor
  • head injury
  • brain infection, meningitis
  • other neurologic problems.

Newer Approval: Xcopri Nov. 2019

Xcopri (cenobamate) was approved by the FDA in late 2019 for the treatment of focal (partial-onset) seizures in adults. Xcopri is classified as a sodium channel blocker and is a C-V controlled substance. Xcopri is typically reserved for adults with treatment-resistant focal seizures.

Xcopri dosing (in detail)

  • Approval was based on results from several studies that enrolled adults with uncontrolled partial-onset seizures. Patients were taking one to three additional anti-epileptic drugs (AEDs).
  • In study 013, a statistically significant 56% reduction in median seizure frequency was seen with Xcopri 200 mg/day versus a 22% reduction with placebo.
  • In Study 017, a 36%, 55% and 55% reduction in median seizure frequency was seen at various doses, versus a 24% reduction with placebo.
  • The most common side effects were somnolence (sleepiness), dizziness, fatigue, diplopia (double vision) and headache.

Epidiolex for Seizures Now FDA-Approved

Epidiolex (cannabidiol or CBD) from GW Pharma is an oral solution for seizures linked with rare and severe forms of epilepsy, for patients one years and older. These serious forms of epilepsy, known as Lennox-Gastaut syndrome and Dravet syndrome, begin in childhood.

In August 2020, the FDA also approved Epidiolex to treat seizures associated with Tuberous Sclerosis Complex (TSC). TSC is a rare disease that causes benign tumors to grow in vital organs of the body and is a leading cause of genetic epilepsy.

View Epidiolex approval history and landmark studies.

Epidiolex is the first FDA-approved drug that contains a purified drug substance derived from marijuana -- CBD -- and the first treatment for Dravet syndrome. Unlike tetrahydrocannabinol (THC), CBD does not cause intoxication or a “high”. Epidiolex is no longer considered a controlled substance.

Common side effects with Epidiolex included:

  • sleepiness
  • sedation and lethargy
  • elevated liver enzymes
  • decreased appetite.

Diacomit for Dravet syndrome

On August 20, 2018, the FDA approved oral Diacomit (stiripentol) for seizures associated with Dravet syndrome in patients 2 years of age and older taking benzodiazepine clobazam (Onfi). Diacomit is not used as monotherapy.

  • Dravet syndrome is a rare genetic seizure condition that usually begins in infancy.
  • Children with Dravet syndrome can have poor language and motor skills, hyperactivity, and difficulty relating to others.

In clinical trials the primary endpoint was the responder rate, defined as more than a 50% reduction in seizures. In two studies, this endpoint was met in 71% and 67% of patients, compared to 5% and 9.1% of patients in the placebo group, respectively.

Common or serious side effects include drowsiness, decreased appetite, nausea, tremor, and increased suicide risk, among others.

Diacomit is manufactured by Biocodex.

Cost of AEDs and Generic Use

Cost of a patient's medication is an important consideration when determining appropriate therapy. This is especially important with AEDs, as noncompliance can lead to risks for breakthrough seizure activity.

Healthplan coverage should be reviewed with the patient. The FDA states that bioavailability between seizure brand name drugs and generic products are within acceptable limits. However, reports do exist of lack of seizure control when generic AED products are substituted for brands.

Patients should be counseled to discuss generic substitution with their healthcare provider.

  • When getting refills, patients and providers may prefer to stay with the same generic manufacturer and product for refills.
  • In some patients, therapeutic blood levels may need to be monitored for a short while after a generic substitution.
  • Patients switching to generic AEDs who then develop an increase in seizure frequency may be considered for a switch back to a their branded product.

Wearable Tech for Seizures

Monitoring seizure activity is moving ahead in the wearable technology device world. Better tracking of seizure activity could help physicians target or adjust drug therapy dosing, and free patients and caregivers of cumbersome diaries and difficult-to-track seizure activity.

Three such devices -- an EEG patch, an arm band system and a wrist-worn monitor, are being developed to record and track seizure activity.

  • The EEG Patch is worn on the scalp for seven days.
  • The Brain Sentinel, is a device worn on the biceps that measures skeletal muscle electrical activity from the skin.
  • The third method relies on existing wearable technology that records heart rate, blood oxygen, and skin electrical conductivity.

Patient Education Improves Outcomes

Primary care physicians and neurologists, nurses, pharmacists and other healthcare providers can serve a vital role in the education of the patient with epilepsy and their family. Patients should learn the importance of a seizure calendar to fine-tune drug treatment.

Patients should also be counseled on the importance of AED compliance, getting timely refills, and continuing treatment unless their physician has authorized a drug taper.

In addition, the patient should learn to identify and avoid any outside triggers such as:

  • lack of sleep
  • stress
  • alcohol.

Nonadherence with drug therapy should be monitored, as well as drug interactions, or recent generic substitution in cases of seizure breakthrough or side effects.

The importance of potential over-the-counter (OTC) drug interactions with AEDs and other drugs should be emphasized to patients; they should consult with their pharmacist prior to using any OTC, vitamin, or herbal dietary supplement.

Join Forces to Gain Strength

Healthcare providers should seek out ways to improve education and health outcomes for patients and families who struggle with epilepsy.

  • A multi-disciplined team approach can bring together the expertise of neurologists, family care physicians, nurses, and pharmacists to enhance treatment modalities for those with epilepsy.
  • The Epilepsy community can join together to gain strength for their cause and support research. Local epilepsy support groups should be sought out, and reliable resources can be found at the Epilepsy Foundation.
  • To voice concerns, ask questions, and stay abreast of the latest epilepsy-related news, patients can also join forces with the Drugs.com Epilepsy Support Group.

Finished: Epilepsy in Adults: A Healthcare Professional's Guide

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Sources

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  • FDA Approves Valtoco (diazepam nasal spray) as a Seizure Rescue Treatment. Drugs.com. Jan. 2020. https://www.drugs.com/newdrugs/fda-approves-valtoco-diazepam-nasal-seizure-rescue-5141.html
  • Pennell P, et al. Management of epilepsy during preconception, pregnancy, and the postpartum period. Up to Date. Accessed Nov. 2, 2020 at https://www.uptodate.com/contents/management-of-epilepsy-during-preconception-pregnancy-and-the-postpartum-period#H1
  • Epidiolex Oral Solution. Package Label. Drugs.com Accessed Nov. 2, 2020 at https://www.drugs.com/pro/epidiolex-oral-solution.html
  • Wearable Devices Aim to Monitor Epileptic Seizures. Drugs.com. Accessed October 28, 2019.
  • American Academy of Neurology. Evidence-based Guideline: Management of an Unprovoked First Seizure in Adults. Clinician Summary. Accessed October 28, 2019 at https://www.aan.com/Guidelines/home/GetGuidelineContent/688
  • Valproate Package Insert. Drugs.com. Accessed October 28, 2019 at https://www.drugs.com/pro/valproate.html
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Further information

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