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Epilepsy in Adults: A Healthcare Professional's Guide

Medically reviewed by L. Anderson, PharmD Last updated on Oct 25, 2018.

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.

About 4% of the U.S. population has epilepsy, which usually begins between ages 5 and 20. However, seizures can begin at any age, and there may be a family history of seizures or epilepsy.

Treatment is important as 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- 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 be life-long therapy. In fact, 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

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

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

Ethosuximide is also a narrow spectrum AED but is used only for absence seizures.

For additional detailed prescribing 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 among efficacy 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) was the most recently approved BZD for use as an adjunct in Lennox-Gastaut Syndrome, a severe form of childhood epilepsy that also causes developmental and behavior problems.

Other BZDs used for seizures include clorazepate, diazepam, 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

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.

Dose: Monotherapy

Adults and children 10 years of age and older: the recommended dose for Qudexy XR monotherapy is 400 mg orally once daily. Qudexy XR monotherapy should be titrated up over a 6 week period.

Children age 2 to less than 10 years of age: Montherapy dosing is based on weight, and should be titrated starting with an initial dose of 25 mg once each night during the first week. Doses may be titrated in 25 to 50 mg increments based on total needed dose, and the titration period should extend 5 to 7 weeks.

Dose: Adjunctive Therapy

Adults (17 Years of Age and Older): The recommended total daily dose of Qudexy XR as adjunctive therapy in adults with partial onset seizures or Lennox-Gastaut Syndrome is 200 mg to 400 mg orally once daily. The recommended total dose for adults with primary generalized tonic-clonic seizures is 400 mg orally once daily. Doses should titrated; in studies the titration period was 8 weeks.

Children (2 to 16 Years): The recommended total daily dose of Qudexy XR as adjunctive therapy for pediatric patients with partial onset seizures, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome is approximately 5 mg/kg to 9 mg/kg orally once daily. Doses should titrated; in studies the titration period was 8 weeks.

Spritam

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 just a sip of liquid. Easier swallowing 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:

  • Keppra, Keppra XR
  • Roweepra
  • Elepsia XR.

Aptiom, Briviact and Carnexiv

Aptiom (eslicarbazepine) was first approved in 2013 as adjunctive therapy for partial-onset seizures. In September 2015, FDA approved once-daily Aptiom (eslicarbazepine ) 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.

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, vomiting.

Briviact was first approved in 2016. Briviact (brivaracetam), an analog of levetiracetam, is used as monotherapry or as an add-on treatment for partial onset seizures in patients age 16 years and older. In clinical trials, common side effects included drowsiness, dizziness, fatigue, and nausea/vomiting. Briviact is classified as a schedule V controlled substance.

In October 2016, an intravenous injection formulation of carbamazepine - known as Carnexiv was approved for short-term use when oral therapy is not an option.

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
  • EEG features
  • Family history
  • Brain tumor
  • Head injury
  • Brain infection, meningitis
  • Other abnormal neurologic findings

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

Use of AEDs in Women of Child-Bearing Age

Teratogenic effects in up to 6% of exposed infants and cognitive declines in the child are major risks of AED use in pregnancy. On the other hand, seizures are also known to be detrimental to the fetus, so risk/benefit must be weighed.

Women who take AEDs and wish to become pregnant should pre-plan 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, valproate should be avoided in pregnant women due to adverse outcomes in the child. The rate of congenital malformations with valproate is about four times higher than other AEDs.

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.

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 seizure activity.

Healthplan coverage should be reviewed with the patient. The FDA states that bioavailability between seizure brand name 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/or 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.

Epidiolex for Seizures Now FDA-Approved

In June 2018 the FDA approved Epidiolex (cannabidiol) [CBD], from GW Pharma, an oral solution for seizures linked with two rare and severe forms of epilepsy, for patients two years and older. These serious forms of epilepsy, known as Lennox-Gastaut syndrome and Dravet syndrome, begin in childhood.

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”. However, Epidiolex was added to schedule V of the Controlled Substances Act in September 2018.

In landmark studies with 516 patients with either seizure type, Epidiolex, taken along with other medications, was shown to be effective in reducing the frequency of seizures when compared with placebo.

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).

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.

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 of often inaccurate seizure diaries.

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

  • Epidiolex Oral Solution. Package Label. Drugs.com Accessed October 25, 2018 at https://www.drugs.com/pro/epidiolex-oral-solution.html
  • Wearable Devices Aim to Monitor Epileptic Seizures. Drugs.com. Accessed October 25, 2018 at https://www.drugs.com/news/wearable-devices-aim-monitor-epileptic-seizures-59319.html
  • American Academy of Neurology. Evidence-based Guideline: Management of an Unprovoked First Seizure in Adults. Clinician Summary. Accessed October 25, 2018 at https://www.aan.com/Guidelines/home/GetGuidelineContent/688.
  • Valproate Package Insert. Drugs.com. Accessed October 25, 2018 at https://www.drugs.com/pro/valproate.html
  • Schachter S. Overview of the management of epilepsy in adults. Up To Date. Accessed October 25, 2018. https://www.uptodate.com/contents/overview-of-the-management-of-epilepsy-in-adults
  • Epilepsy Guide: Harvard Health Guide. Drugs.com. Accessed October 25, 2018 at https://www.drugs.com/health-guide/epilepsy.html
  • Morrell MJ. Folic Acid and Epilepsy. Epilepsy Currents. 2002;2(2):31-34. Accessed October 25, 2018 at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC320966/
  • Schachter S. Antiepileptic drugs: Mechanism of action, pharmacology, and adverse effects. Up To Date. Accessed October 25, 2018. https://www.uptodate.com/contents/antiseizure-drugs-mechanism-of-action-pharmacology-and-adverse-effects
  • Epilepsy. Mayo Clinic Disease Reference. Accessed October 25, 2018 at https://www.drugs.com/mcd/epilepsy

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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