Download Epilepsy 101: Getting Started

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Module Three: Treatment of
Epilepsy
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Module Three: Objectives
Upon completion of Module Three the
participant will:
Describe
epilepsy
the main treatment options for
Identify
factors essential in the selection of
appropriate medications for epilepsy
Review
the indications for epilepsy surgery
Discuss
the benefits of dietary therapy for
epilepsy
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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
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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
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are treated if:
two or more seizures
abnormal imaging
abnormal neurological exam
abnormal EEG
family history of seizures
 Treatment
begins with one drug
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Antiepileptic Drugs (AEDs)
More accurately called ‘Anti-Seizure Drugs’
Goals of medication therapy:
No
seizures
No
side effects – tailor side effect profile to
patient-specific factors
Improvement
in quality of life
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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
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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
strengths
in different dosage
 Affordable, covered
health insurance
by
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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
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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
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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
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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
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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
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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
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Considerations for AED Choice
 Ability
to give alone (monotherapy) or together
with other AEDs (polytherapy)
 Side-effect
 Need
for laboratory monitoring
 Drug-drug
 Cost
profile
and drug-food interactions
and availability
 Patient’s
ability to manage the medication(s)
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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
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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
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1st Generation AEDs
 1857-
Bromides
 1912-Phenobarbital
 1938-Phenytoin
(Dilantin)
 1954 1960-
Primidone
Ethosuximide
(Zarontin)
 1974-Carbamazepine
(Tegretol)
 1975
Clonazepam
(Klonopin)
 1978- Valproate
(Depakote)
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2nd Generation AEDs
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1993- Felbamate (Felbatol)
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2000- Zonisamide (Zonegran)
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1993- Gabapentin (Neurontin)
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2005- Pregabalin (Lyrica)
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1995-Lamotrigine (Lamictal)
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2009- Lacosamide (Vimpat)
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1997-Topiramate (Topamax)
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2009- Rufinamide (Banzel)
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2010-ACTH (Acthar)
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2011- Clobazam (Onfi)
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2012 – Ezogabine (Potiga)
Tiagabine (Gabitril)
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1999- Levetiracetam (Keppra)
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2000- Oxcarbazepine (Trileptal
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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/consensusstatements/drug-substitution
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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
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Types of Side Effects
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Dose-related: the higher the dose, the more
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Idiosyncratic: Occurs irrespective of dose
likely the effect
• Common: drowsiness, irritability, nausea,
clumsiness, imbalance, blurry or double vision
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Changes in appetite or weight change,
osteopenia or osteoporosis, cosmetic effects,
tremors, fatigue, cognitive effects, mood changes
Allergic: i.e. rash, anaphylaxis
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Serious Side Effects
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Prolonged fever
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Pinpoint bleeding
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Rash
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Weakness
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Nausea/vomiting
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Fatigue
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Severe sore throat
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Swollen glands
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Mouth ulcers
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Lack of appetite
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Easy bruising
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Abdominal pain
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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
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Rescue Treatments
Used to stop prolonged or clusters of
seizures
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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
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Rescue Treatments
General Instructions
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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:
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Seizure Action Plans for School Settings
My Seizure Response Plans
My Epilepsy Diary
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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
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Epilepsy Surgery
Indications
 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
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Epilepsy Surgery
Presurgical Evaluation
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Determine that seizures are refractory to AEDs
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Video EEG telemetry to localize seizures
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Scans to identify possible causes and location of seizure
focus (CT, MRI, PET, SPECT, MEG)
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Multidisciplinary evaluations – medicine, nursing, psychiatry,
social work, psychology
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Neuropsychological testing to evaluate cognitive function,
assist in localizing seizure focus
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Wada test – to identify location of language and memory
functions
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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
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Vagus Nerve Stimulation (VNS)
Therapy
 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
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VNS Therapy- Use of Magnet
Stop side effects:
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Magnet temporarily stops
stimulation
Hold magnet over
generator in chest for at
least 6 seconds.
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Stimulation will not be
delivered as long as the
magnet is over the
generator.
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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
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Dietary Therapies for Epilepsy
 Ketogenic
 Modified
 Low
Diet (KD)
Atkins Diet (MAD)
Glycemic Index Treatment (LGIT)
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Dietary Therapies
Indications and General Tips
 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