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Antiepileptic Drugs

By: DR Mehran Homam

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

Seizure Types

Primary Generalized

– Tonic-clonic (“grand mal”)– Absence (“petit mal”)– Myoclonic– Tonic– Atonic (“drop attacks”)

Partial

– simple vs. complex (“psychomotor”)

“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

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

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

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

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

Barbiturates (primidone [Mysoline] and phenobarbital)

Effective

Once a day (phenobarbital)

cheap

IV form (phenobarbital)

Sedation and cognitive effects

Withdrawal

Other old medications

acetazolamide (Diamox)

clonazepam (Klonopin) & lorazepam (Ativan)

ethosuximide (Zarontin)

ketogenic diet

ACTH/steroids

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

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

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)

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

tiagabine (Gabitril)

ADVANTAGES– Minimal effect on other

medications

DISADVANTAGES– Dose is dependent on

concurrent AEDs– Anxiety– Occasionally makes

some seizure types worse

levetiracetam (Keppra)

ADVANTAGESNo interactionsMinimal liver

metabolismWorks for most

seizure typesCan start quicklyWell toleratedLiquid formulation

DISADVANTAGESBehavioral/psych side

effectsTwice per day

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

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

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

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

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)

Drugs that decrease efficacy of oral contraceptives

Dilantin (phenytoin)

Tegretol, Carbatrol (carbamazepine)

Phenobarbital

Mysoline (primidone)

Topamax (topiramate) at higher doses

Trileptal (oxcarbazepine)

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