Antiepileptic Drugs. Overview Seizures are sudden episodes of neurological dysfunction caused by...
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Antiepileptic Drugs
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Overview
Seizures are sudden episodes of neurological dysfunction caused by abnormal electrical activity of the brain
Seizures are common10% of the population will have a seizure during their
lifetime (about half are seizures with fever in infancy)Epilepsy: recurrent, unprovoked seizures
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Seizure Types
Primary Generalized
– Tonic-clonic (“grand mal”)– Absence (“petit mal”)– Myoclonic– Tonic– Atonic (“drop attacks”)
Partial
– simple vs. complex (“psychomotor”)
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“Older” AEDs
Phenobarbital 1912
Dilantin (phenytoin) 1938
Mysoline (primidone) 1952
Zarontin (ethosuximide) 1960
Tegretol (carbamazepine) 1974
– Also Tegretol-XR and CarbatrolDepakote, Depakene (valproate) 1978
– now IV form and Depakote-ER
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Newer AEDS
Felbatol (felbamate) 1993
Neurontin (gabapentin) 1994
Lamictal (lamotrigine) 1995
Topamax (topiramate) 1996
Gabitril (tiagabine) 1998
Keppra (levetiracetam) 1999
Trileptal (oxcarbazepine) 2000
Zonegran (zonisamide) 2000
Lyrica (pregabalin) 2005
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Carbamazepine (Tegretol)
First line drug for partial szs for years
Two long-acting forms now avail (2X/day)
Side effects at just above therapeutic range
Not effective for some seizure types
Must start slowly due to side effects
No IV form
Lots of interactions
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Phenytoin (Dilantin)
First line for partial seizures for years
Once a day
IV form
Side effects at just avove therapeutic range
Not effective for some seizure types
Side effects: imbalance, sedation, cognitive, gum problems, osteoporosis
Many interactions
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Valproate (Depakote)
Works for all seizure types
Around for decades
Rare allergic reactions
Helps prevent migraines
New IV form
New long-acting form
Side effects, esp. weight gain & tremor
Menstrual irregularities
Not best for pregnancy
Significant drug interactions
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Barbiturates (primidone [Mysoline] and phenobarbital)
Effective
Once a day (phenobarbital)
cheap
IV form (phenobarbital)
Sedation and cognitive effects
Withdrawal
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Other old medications
acetazolamide (Diamox)
clonazepam (Klonopin) & lorazepam (Ativan)
ethosuximide (Zarontin)
ketogenic diet
ACTH/steroids
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Newer AEDs
Equally effective as older AEDs
Most better tolerated than older AEDs
Most have fewer interactions with other medications than older AEDs
All expensive
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gabapentin (Neurontin)
ADVANTAGESNo interactions with
other drugsExtremely rare
“allergic” reactionsCan be started quicklyWell-toleratedTreats pain, anxiety,
restless leg syndrome
Generic availabilityLiquid formulation
DISADVANTAGESThree-times-a-day
dosingDoes not treat all
types of seizures
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lamotrigine (Lamictal)
ADVANTAGES– Minimal effect on
other medications– Works for all types of
seizures– Very well tolerated– Minimal sedation– Probably safe in
pregnancy– Approved for >2 y.o. – Monotherapy
DISADVANTAGES– Rash if started
quickly Must start slowly (~2 months to full dose)
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topiramate (Topamax)
ADVANTAGES– Minimal interactions with
other medications– Probably works for all
seizure types– Approved for >2 y.o – Sprinkle form– Approved for
monotherapy– Weight loss– Approved for migraine
prevention
DISADVANTAGES– Cognitive side
effects– 1-2% renal stones– tingling/pins and
needles– Can decrease
efficacy of oral contraceptives
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tiagabine (Gabitril)
ADVANTAGES– Minimal effect on other
medications
DISADVANTAGES– Dose is dependent on
concurrent AEDs– Anxiety– Occasionally makes
some seizure types worse
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levetiracetam (Keppra)
ADVANTAGESNo interactionsMinimal liver
metabolismWorks for most
seizure typesCan start quicklyWell toleratedLiquid formulation
DISADVANTAGESBehavioral/psych side
effectsTwice per day
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oxcarbazepine (Trileptal)
As effective and better tolerated than Tegretol
Fewer interactions than Tegretol
Approved for children > 4
Approved for first-line monotherapy
Not for all seizure types
Low sodium, esp if on diuretics also
Lessens effectiveness of birth control pill
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zonisamide (Zonegran)
Used in Japan for many years
Works for all seizure types
Approved for childrenOnce dailyWeight lossRecent addition of 25 mg
capsules
1-2% kidney stonesOccasional psychiatric or
sedative side effectsSulfa drug
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Intranasal or Buccal Midazolam
Safe and effective (studies in UK, Israel): 5-10 mg in adultsEasy to useLess social stigmaNot approved in US for this usageNot easy to obtain (controlled substance) in a convenient formShorter acting than Diastat
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Considerations in choosing an AED
Side effect profileEfficacy and correct seizure/syndrome diagnosisConvenience (doses/day, etc)
– Once/day: phenobarb, Dilantin, Zonegran, ?LamictalCostDrug interactions/potential for future problemsNon-epileptic indications for AEDs
– Pain: Neurontin, Topamax, Tegretol, Trileptal, Lyrica, others
– Headaches: Depakote, Topamax, others– Psychiatric: Neurontin, Depakote, Tegretol, Lamictal,
Lyrica, othersConcurrent medical problems
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Weight Issues
Risk of weight gain– Depakote (valproate)– Neurontin (gabapentin)
and Lyrica (pregabalin)• Less so
“Risk” of weight loss– Topamax (topiramate)– Zonegran (zonisamide)– Felbatol (felbamate)
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Drugs that decrease efficacy of oral contraceptives
Dilantin (phenytoin)
Tegretol, Carbatrol (carbamazepine)
Phenobarbital
Mysoline (primidone)
Topamax (topiramate) at higher doses
Trileptal (oxcarbazepine)
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Lifestyle changes to minimize seizures
Avoid sleep deprivation
Avoid alcohol
Treat fevers quickly
Occasional patients should avoid specific factors such as strobe lights, etc
Pill boxes/reminders