Management of Epilepsy
Robert L. Macdonald M.D., Ph.D.
Department of Neurology
Vanderbilt University Medical Center
Nashville, TN
Management of Epilepsy
– Learning Objectives
Identify the differences between seizures
and epilepsy.
Describe the management of a patient after
a first seizure.
Describe the management of a patient with
epilepsy.
Discuss the management of epilepsy in
women of child bearing age.
Epidemiology of Seizures and Epilepsy
Seizures
Incidence: approximately 80/100,000 per year
Lifetime prevalence: 9%
(1/3 benign febrile convulsions)
Epilepsy
Chronic recurring, unprovoked seizures
Incidence: approximately 45/100,000 per year
Point prevalence: 0.5-1%
Seizure Classification
Partial seizures (focal or local origin)
Simple partial seizures with:
motor signs
somatosensory or special sensory symptoms
autonomic symptoms or signs
psychic symptoms (disturbance of higher cerebral
function)
Complex partial seizures with:
Impaired consciousness
Presence and nature of aura (simple partial origin)
Automatisms and other motor activity
Secondary generalized seizures
Seizure Classification
Primary generalized seizures (bilateral origin)
Absence
Myoclonic
Atonic
Tonic
Tonic-clonic
Epilepsy Syndromes
Partial epilepsies
Idiopathic
Symptomatic
Cryptogenic
Generalized epilepsies
Idiopathic
Symptomatic
Cryptogenic
Undetermined epilepsies
Special syndromes
Questions Raised by a First Seizure
Seizure or not?
Partial (focal) or generalized onset?
Evidence of CNS dysfunction?
Seizure type? Syndrome type?
Metabolic or other precipitant?
Studies?
Treatment - start an antiepileptic drug (AED)?
Evaluation of a First Seizure
History, physical exam
Blood tests: CBC, electrolytes, glucose, Ca, Mg,
hepatic and renal function
Lumbar puncture only if meningitis or
encephalitis suspected and potential for brain
herniation is ruled out
Blood or urine screen for drugs
Partial seizures are presumed to be due to a
structural lesion unless proven otherwise.
Electroencephalogram if indicated
CT or MR brain scan if indicated
Evaluation of a First Seizure-Precipitants
Metabolic and Electrolyte Imbalance
Low (occ high) blood glucose, Na, Ca, Mg
Stimulant/other proconvulsant intoxication
IV drug use, cocaine, ephedrine, herbal remedies
Sedative/medication reduction
Sleep deprivation, stress
Hormonal variations
Infection
Medical Management of First Seizure
Whether or not to treat a first seizure is controversial.
The risk of recurrence within 5 years is 16-62% and
with a single unprovoked seizure (normal EEG and
MRI) is about 40%.
Abnormal imaging, abnormal EEG or + family history
of epilepsy increase recurrence risk.
Quality of life issues are important for AED Rx.
Was the seizure “precipitated”? If so, Rx with an
AED is not necessary – remove the precipitant.
Treat a first seizure if there is a high likelihood of
developing epilepsy (recurrence rate is reduced by
AED treatment).
Medical Management of Epilepsy
First diagnose seizure type(s), epilepsy
syndrome, and etiology.
Try pharmacotherapy first (unless etiology
necessitates surgery).
Use monotherapy with an AED that is the most
appropriate for seizure type/epilepsy syndrome
(but other considerations also play a role), and
safest.
Start at a low dose, increase slowly.
Medical Management of Epilepsy
Try to reach the lowest effective dose.
Target: seizure control with no side effects
We may use drug levels if needed (but we should
not be bound by the drug levels)
If drug A fails, try drug B monotherapy.
Try polytherapy if monotherapy fails.
anticipate drug interactions
Choosing an AED
Seizure type
Epilepsy syndrome
Pharmacokinetic profile
Interactions/other medical conditions
Efficacy
Expected adverse effects
Useful as monotherapy - simplifies treatment
and reduces adverse effects
Cost
Antiepileptic Drugs
old
new
Phenytoin (Dilantin)
Felbamate (Felbatol) *
Carbamazepine
(Tegretol, Carbatrol)
Gabapentin (Neurontin) ¶
Valproate (Depakote)
Topiramate (Topamax) *
Phenobarbital
Primidone (Mysoline)
Clonazepam (Klonopin)
Ethosuximide (Zarontin)
Methsuximide (Celontin)
Lamotrigine (Lamictal) *
Tiagabine (Gabitril)
Levetiracetam (Keppra) ¶
Oxcarbazepine (Trileptal) *
Zonisamide (Zonegran)
Pregabalin (Lyrica)
* new drugs approved to be used in monotherapy
¶ no monotherapy indication, but comparative monotherapy trial
Spectrum of Efficacy of Old AEDs
AED
Partial
Absence
Myoclonic
Phenytoin
++
-
-
Carbamazepine
++
-
-
Valproate
++
++
++
Primidone
+
-
-
Phenobarbital
+
-
-
Clonazepam
+
+
+
Methsuximide
+
+
+
Ethosuximide
-
++
-
Spectrum of Efficacy of New AEDs
AED
Partial
Absence
Myoclonic
Felbamate (Felbatol)
+
+
+
Gabapentin (Neurontin)
+
-
-
Lamotrigine (Lamictal)
+
+
+/-
Topiramate (Topamax)
+
+/-
+
Tiagabine (Gabitril)
+
-
-
Levetiracetam (Keppra)
+
+
+
Oxcarbazepine (Trileptal)
+
-
-
Zonisamide (Zonegran)
+
+
+
Pregabalin (Lyrica)
+
-
-
Partial Seizures- The First AED
First AED - in general:
Carbamazepine (Tegretol, Carbatrol)
Phenytoin (Dilantin)
Oxcarbazepine (Trileptal)
Topiramate (Topamax)
Valproate (Depakote)
First AED - special situations when other
AEDs may be considered
Gabapentin (Neurontin)
Lamotrigine (Lamictal)
Levetiracetam (Keppra)
?Zonisamide (Zonegran), ?Pregabalin (Lyrica)
Generalized Seizures- The First AED
Generalized onset seizures
Absence:
valproate* = ethosuximide
Myoclonic:
valproate, clonazepam
Tonic-clonic:
valproate = phenytoin, carbamazepine
*
the risk of valproate-induced hepatic failure must be carefully weighed in
young children
AED Initiation and Monitoring
Discuss likely and unlikely but important
adverse effects.
Discuss likelihood of success.
Discuss recording/reporting seizures (seizure
calendar), adverse effects, potential
precipitants.
Obtain appropriate “baseline” laboratory tests
CBC, platelets, LFTs
Initiate therapy with an appropriate dose.
Monitor AED levels when appropriate.
AED Interactions
AEDs that induce metabolism of other drugs:
carbamazepine, phenytoin, phenobarbital
AEDs that inhibit metabolism of other drugs:
valproate, felbamate
AEDs that are highly protein bound: valproate,
phenytoin, tiagabine
Other drugs may alter metabolism or protein
binding of antiepileptic drugs
AED Serum Concentrations
In general AED serum concentrations can be
used as a guide for evaluating the efficacy of
medication therapy for epilepsy.
Serum concentrations are useful when
optimizing AED therapy, assessing compliance,
or teasing out drug-drug interactions.
They should be used to monitor
pharmacodynamic and pharmacokinetic
interactions.
Evaluation After Seizure Recurrence
Progressive pathology?
Avoidable precipitant?
If on an AED
Problem with compliance or pharmacokinetic factor?
Increase dose?
Change medication?
If on multiple AEDs
Convert to monotherapy from polytherapy?
Eliminate sedative drugs first
Withdraw antiepileptic drugs slowly over several months
If not on AED
Start therapy?
Preconception Counseling and
Teratogenicity
Preconception information should be offered to all
females with childbearing potential since most
major malformations occur at an early stage in
pregnancy, often before the woman knows she is
pregnant.
If changes in AED medication are to be made, they
should be completed before conception.
If AED treatment is needed, a single agent is
preferred.
Preconception Counseling and
Teratogenicity
The use of phenytoin, valproate, carbamazepine,
lamotrigine, and phenobarbital has been associated
with an increased risk of major malformations and
minor morphological anomalies. (3% with
carbamazepine or lamotrigine, 7% with valproate, and
15% with two or more AEDs).
It is not known if vigabatrin, gabapentin,
levetiracetam, topiramate, oxcarbazepine,
pregabalin, and tiagabine are associated with a risk
of fetal abnormalities in humans.
Women with epilepsy who are planning a pregnancy
should take folic acid 1 mg/day in the preconception
period and throughout the pregnancy; vitamin K
should be used in the last month of pregnancy in
women on enzyme-inducing AEDs.
Contraception and AEDs
For women on nonenzyme-inducing AEDs (valproate,
benzodiazepines, vigabatrin, gabapentin, tiagabine,
levetiracetam, pregabalin), all current contraceptive
methods are suitable.
Hormonal forms of contraception are affected by
enzyme-inducing AEDs (phenytoin, barbiturates,
carbamazepine, oxcarbazepine, topiramate [>200
mg/day], and lamotrigine); women taking these
forms of contraception should be counseled on
their risks and benefits.
Non-Drug Treatment/Lifestyle
Modifications
Adequate sleep
Avoidance of alcohol, stimulants, etc.
Avoidance of non-precipitants
Stress reduction — specific techniques
Adequate diet
Exercise
Discontinuing AEDs
Seizure free 2 years implies overall >60%
chance of successful withdrawal in some
epilepsy syndromes
Favorable factors
Control achieved easily on one drug at low dose
No previous unsuccessful attempts at withdrawal
Normal neurologic status and EEG?
Primarily generalized seizures except JME
“Benign” syndrome
Consider relative risks/benefits (driving,
pregnancy)
Questions?