+Module Three: Treatment of Epilepsy

+Module Three: Objectives

Upon completion of Module Three the participant will:Describe the main treatment options for epilepsyIdentify factors essential in the selection of appropriate medications for epilepsyReview the indications for epilepsy surgery Discuss the benefits of dietary therapy for epilepsy

+Treatment of Epilepsy

Individuals with epilepsy have a variety of treatment options Medications are the first option and the mainstay

of treatment for most people

AEDs treat the symptoms, not the underlying disease

Surgical procedures and implantable devices are also options that are considered if seizures persist

Dietary therapies provide another treatment option in some patients when medicines don’t work

+Decision to Treat with Medications Most patients with first time seizures are not placed on medications

Medications to treat seizures are usually called antiepileptic drugs or AEDs

Patients are treated if: two or more seizures abnormal imaging abnormal neurological exam abnormal EEG family history of seizures

Treatment begins with one drug

+Antiepileptic Drugs (AEDs)

Goals of medication therapy:No seizures

No side effects – tailor side effect profile to patient-specific factors

Improvement in quality of life

More accurately called ‘Anti-Seizure Drugs’

+Antiepileptic Medications (AED)

Good oral absorption and bioavailability

Most metabolized in liver but some excreted unchanged in kidneys

1st generation AEDs generally have more severe CNS sedation than newer drugs

Drugs chosen based on mechanism of action, side effect profile, and impact on comorbid conditions, ie. migraine, depression

Add-on therapy is used when a single drug does not completely control seizures

+Ideal Characteristics for AEDs

Few adverse effects

High CNS penetrance

Rapid onset of action

No or few drug-drug interactions

Long half-life for daily or twice a day dosing

Intravenous route available

Oral liquid preparations important for children and people with impaired swallowing

Available in different dosage strengths

Affordable, covered by health insurance

+Things to keep in mind…

 Treatment with medication is successful for a large percentage of individuals, but at least 30 to 40% don’t respond to current AEDs

Multiple dosing times for medications may lessen adherence

 Certain types of medications work best for certain forms of epilepsy

+Medication Adherence

The extent to which a person takes medication as prescribed Also referred to as compliance Using a self-management model, adherence

is one aspect of medication-taking behaviors

Missed AEDs are one of the most common reasons for breakthrough seizures

Complex medication regimes, poor memory, and cost are barriers to adherence

+Pharmacokinetics

Absorption: How long it takes for medicine to be absorbed into the bloodstream Determined by route of intake, may be affected

by food Absorption rate can vary for different medicines Meds that may affect rate of absorption should

not be given at same time as AEDs, i.e. antacids

Distribution: How the drug is distributed through the body AEDs with a high degree of protein binding tend

to have more drug interactions

+Pharmacokinetics

Metabolism and Elimination: Drugs may be broken down in the liver and excreted through the kidneys AEDs metabolized by the liver tend to have

more drug interactions

Bioavailability: How much drug gets into the brain to work as intended. The net result of the absorption, distribution,

metabolism, and elimination process

+Drug Concentration: Establishing AED Doses

Some drugs require a large initial dose to achieve a desired concentration in the body, called a ‘loading dose’

Some AEDs are tolerated better when started at slowly at low doses

The dose necessary to MAINTAIN a desired concentration over time is called the ‘maintenance dose’ and may vary according to patient and drug specific factors

+Laboratory Monitoring

Serum drug levels serve as a guideline in determining therapeutic dosing

Serum levels of newer drugs may not be as important since the therapeutic window for dosing is much larger

Additional monitoring (i.e. liver function tests, CBC, or renal function) may be needed, depending on specific drug

+Considerations for AED Choice

Ability to give alone (monotherapy) or together with other AEDs (polytherapy)

Side-effect profile

Need for laboratory monitoring

Drug-drug and drug-food interactions

Cost and availability

Patient’s ability to manage the medication(s)

+General Instructions

Patients must take medications as prescribed on a daily basis to maintain a therapeutic blood level to prevent seizures

Patients should not abruptly stop medications – raises risk for seizure emergencies

Factors that can influence how the drug gets into the body, works in the body, and is metabolized and eliminated can interfere with the serum blood drug levels and interact with other medications

+1st and 2nd Generation AED’s

The oldest drugs used in the treatment of epilepsy include phenobarbital, introduced in 1912, and phenytoin (Dilantin), in use since 1938-these drugs are considered as 1st generation

2nd generation AED’s have been in place since the early 1990’s

+1st Generation AEDs

1857- Bromides

1912-Phenobarbital

1938-Phenytoin (Dilantin)

1954- Primidone

1960- Ethosuximide (Zarontin)

1974-Carbamazepine (Tegretol)

1975 Clonazepam (Klonopin)

1978- Valproate (Depakote)

+ 2nd Generation AEDs

1993- Felbamate (Felbatol)

1993- Gabapentin (Neurontin)

1995-Lamotrigine (Lamictal)

1997-Topiramate (Topamax) Tiagabine (Gabitril)

1999- Levetiracetam (Keppra)

2000- Oxcarbazepine (Trileptal

2000- Zonisamide (Zonegran)

2005- Pregabalin (Lyrica)

2009- Lacosamide (Vimpat)

2009- Rufinamide (Banzel)

2010-ACTH (Acthar)

2011- Clobazam (Onfi)

2012 – Ezogabine (Potiga)

+Generic Drugs

Generic versions are available for many epilepsy medications

While FDA states that generic medications are comparable to brand name AEDs, people have reported differences in seizure control and/or side effects during switches between generic to brand, or between different generic formulations

Patients should discuss the use of generics with their provider

For more information: AES consensus statement on generic drug substitution http://www.aesnet.org/go/press-room/consensus-statements/drug-substitution

+Medication Side Effects

Awareness of common side effects is important

Side effects can be unpredictable What works well for one person, may not

work well for the next

Side effects can be dose dependent Often depends on person's chemistry and

metabolism, height, weight, etc. Most common dose dependent side effects

affect the CNS

+Types of Side Effects

• Dose-related: the higher the dose, the more likely the effect• Common: drowsiness, irritability, nausea,

clumsiness, imbalance, blurry or double vision

• Idiosyncratic: Occurs irrespective of dose• Changes in appetite or weight change,

osteopenia or osteoporosis, cosmetic effects, tremors, fatigue, cognitive effects, mood changes

• Allergic: i.e. rash, anaphylaxis

+

Serious Side Effects Prolonged fever

Rash

Nausea/vomiting

Severe sore throat

Mouth ulcers

Easy bruising

Pinpoint bleeding

Weakness

Fatigue

Swollen glands

Lack of appetite

Abdominal pain

+Drug Interactions

How well an AED works may be affected by other medications a person is taking

Interactions may occur between AEDs or between AEDs and other prescription or over-the-counter medications, for example, warfarin, antibiotics, and other commonly used medications

+Rescue Treatments

Rectal diazepam gel (Diastat™) approved by FDA for out of hospital use by non-medical people

PRN benzodiazepines are first line treatment and can be given in the home, community, ambulance or hospital.

Autoinjectors and intranasal forms are being tested. Vagus nerve stimulator magnets - non-drug

intervention for seizure first aid Rescue Treatments do not replace routine seizure

first aid

Used to stop prolonged or clusters of seizures

+Rescue Treatments

Rescue AEDs can be given by mouth, bucally, rectally or intravenously, depending on the setting and who is giving the AED.

Patients should have specific instructions on when to use rescue AEDs or VNS magnet

Include when to seek medical care and emergency services in seizure plans and protocols.

Resources from Epilepsy Foundation: Seizure Action Plans for School Settings My Seizure Response Plans My Epilepsy Diary

General Instructions

+When Seizures Do Not Respond to AEDs

Patients whose seizures are not controlled after 2 or more trials of appropriate medications should be referred to the next level of care for appropriate evaluation and treatment. For example,

Refer to a neurologist if seizures persist after 3 months of care by a primary care provider

Refer to an epilepsy specialist if seizures persist despite treatment with general neurologist for 12 months

+Epilepsy Surgery

Failure of AEDs to control seizures – refractory epilepsy

Ability to identify focus of seizure generation in the brain

Able to remove focus or operate safely

Seizures are ‘disabling’ – consider impact of seizures on quality of life

Benefits versus risks of surgery and of refractory epilepsy

Indications

+Epilepsy Surgery

Determine that seizures are refractory to AEDs

Video EEG telemetry to localize seizures

Scans to identify possible causes and location of seizure focus (CT, MRI, PET, SPECT, MEG)

Multidisciplinary evaluations – medicine, nursing, psychiatry, social work, psychology

Neuropsychological testing to evaluate cognitive function, assist in localizing seizure focus

Wada test – to identify location of language and memory functions

Presurgical Evaluation

+Epilepsy Surgery

Most common type of epilepsy surgery is resection in temporal or frontal lobe

Outcomes of surgery depend on the type and location of surgery, whether all or most of the epileptogenic area was removed and other patient-specific factors

+Vagus Nerve Stimulation (VNS) Therapy

30

Used as adjunctive therapy A programmable pulse

generator implanted subcutaneously in upper left chest

Electrode wrapped around the left vagus nerve

Exact mechanism of action not known

Stimulation-related side effects may include hoarseness, coughing and shortness of breath

+VNS Therapy- Use of Magnet

Stop side effects: Magnet temporarily

stops stimulation

Hold magnet over generator in chest for at least 6 seconds.

Stimulation will not be delivered as long as the magnet is over the generator.

To restart stimulation, remove the magnet.

Seizure first aid:

Magnet may activate additional burst of stimulation

Swipe magnet over generator in chest for one second (“one one-thousand one”)

Wait 60 seconds, then repeat, or as recommended in seizure action plan

+ Dietary Therapies for Epilepsy

Ketogenic Diet (KD)

Modified Atkins Diet (MAD)

Low Glycemic Index Treatment (LGIT)

+Dietary Therapies

For people with refractory epilepsy, when medications don’t work or are not tolerable

May allow reduction in AEDs if seizures can be controlled.

Ketogenic diet is the most restrictive, may require a hospitalization and few days of fasting to start it. Difficult for older children and adults to tolerate

Modified Atkins and Low Glycemic diets are less restrictive and easier to tolerate by many people

Indications and General Tips