Epilepsy in Adults: A Healthcare Professional's Guide
Medically reviewed on Oct 14, 2017 by L. Anderson, PharmD
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.
- A partial 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 focal 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 not well accepted and 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 focal and generalized onset seizures include:
- felbamate (Felbatol)
- lamotrigine (Lamictal)
- clobazam (Onfi)
- valproic acid (Depakene, Stavzor)
- divalproex sodium (Depakote)
- levetiracetam (Keppra, Keppra XR, Spritam)
- perampanel (Fycompa)
- rufinamide (Banzel)
- topiramate (Topamax, Qudexy XR, Trokendi XR)
- zonisamide (Zonegran)
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 focal (partial) seizures or those that spread bilaterally include:
- brivaracetam (Briviact)
- carbamazepine (Tegretol, Carbatrol, Equetro, Carnexiv Injection)
- eslicarbazepine (Aptiom)
- ezogabine (Potiga)
- lacosamide (Vimpat)
- gapapentin (Gralise, Horizant, Neurontin, Gabarone)
- oxcarbazepine (Oxtellar XR, Trileptal)
- phenytoin (Dilantin, Phenytek)
- pregablin (Lyrica)
- primidone (Mysoline)
- vigabatrin (Sabril)
- tiagabine (Gabitril)
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.
2014-2015 FDA Approval: Qudexy XR
Latest FDA Approvals:
- In March 2014, Qudexy XR was first approved as an add-on treatment to other medicines for patients two and older with POS, primary generalized tonic-clonic seizures, or seizures associated with Lennox-Gastaut syndrome.
- Qudexy XR (topiramate) - In June 2015, once-a-day Qudexy XR (topiramate extended-release capsule) was approved as initial monotherapy for patients two and older with partial-onset seizures (POS) or primary generalized tonic-clonic seizures. Previously this use was only approved in patients 10 and older.
2015 FDA Approval: Spritam
Latest FDA Approvals:
- Spritam (levetiracetam) - In August 2015, the FDA approved oral Spritam (levetiracetam), the first drug made with 3D technology. Spritam is used as add-on therapy for partial onset seizures, myoclonic seizures and primary generalized tonic-clonic seizures in adults and children with epilepsy.
- 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. Levetiracetam is also available in generic and other brand names known as Keppra, Keppra XR and Elepsia XR.
Recent FDA Approvals: Aptiom, Briviact, Carnexiv
Latest FDA Approvals:
- Aptiom - 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. The most common treatment-related adverse effects included headache, dizziness, fatigue, somnolence, and nausea. Aptiom was first approved in 2013 as adjunctive therapy for partial-onset seizures.
- Briviact - In February 2016, FDA approved Briviact (brivaracetam), an analog of levetiracetam, as an add-on treatment for partial onset seizures in patients age 16 years and older with epilepsy. In clinical trials, Briviact common side effects included drowsiness, dizziness, fatigue, and nausea/vomiting. In September 2017, the FDA also [approved monotherapy](https://www.drugs.com/history/briviact.html) use of Briviact for partial-onset (focal) seizures in patients 16 years and older with epilepsy. Briviact is classified as a schedule V controlled substance, which may have a low potential for abuse.
- Carnexiv - In October 2016, an intravenous injection formulation of carbamazepine - Carnexiv from Lundbeck - 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:
- 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
- Teratogenic effects
Use of AEDs in Women of Child-Bearing Age
Teratogenic effects in up to 6 percent 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. 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 U.S. Food and Drug Administration (FDA) approved Epidiolex (cannabidiol) [CBD], from GW Pharma, an oral solution for the 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”.
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, and decreased appetite, among others
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.
As reported in December of 2015 at the American Epilepsy Society meeting, 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. Another, 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 aldo 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, or 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 hands 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
- American Academy of Neurology. Evidence-based Guideline: Management of an Unprovoked First Seizure in Adults. Clinician Summary. April 2015. Accessed 10/13/2017 at https://www.aan.com/Guidelines/home/GetGuidelineContent/688.
- Fresenius Kabi USA. Valproate Package Insert. Drugs.com. Revised 10/2015. Accessed 10/13/2017 at https://www.drugs.com/pro/valproate.html
- Schachter S. Overview of the management of epilepsy in adults. Up To Date. Updated November 2015. Accessed 10/13/2017.
- Epilepsy Guide: Harvard Health Guide. Drugs.com. Accessed 10/13/2017 at https://www.drugs.com/health-guide/epilepsy.html
- Morrell MJ. Folic Acid and Epilepsy. Epilepsy Currents. 2002;2(2):31-34. Accessed 10/13/2017 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 10/13/2017.
- Epilepsy. Mayo Clinic Disease Reference. Accessed 10/13/2017 at https://www.drugs.com/mcd/epilepsy