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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 common 10% 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 Dilantin (phenytoin) Mysoline (primidone) Zarontin (ethosuximide) Tegretol (carbamazepine) Depakote, Depakene (valproate) 1978 1912 1938 1952 1960 1974

Also Tegretol-XR and Carbatrol


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)
ADVANTAGES DISADVANTAGES No interactions with Three-times-a-day other drugs dosing Extremely rare Does not treat all allergic reactions types of seizures Can be started quickly Well-tolerated Treats pain, anxiety, restless leg syndrome Generic availability Liquid formulation

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)

ADVANTAGES No interactions Minimal liver metabolism Works for most seizure types Can start quickly Well tolerated Liquid formulation

DISADVANTAGES Behavioral/psych side effects Twice 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 children Once daily Weight loss Recent addition of 25 mg capsules

1-2% kidney stones Occasional psychiatric or sedative side effects Sulfa drug

Intranasal or Buccal Midazolam Safe and effective (studies in UK, Israel): 5-10 mg in adults Easy to use Less social stigma Not approved in US for this usage Not easy to obtain (controlled substance) in a convenient form Shorter acting than Diastat

Considerations in choosing an AED


Side effect profile Efficacy and correct seizure/syndrome diagnosis Convenience (doses/day, etc)
Once/day: phenobarb, Dilantin, Zonegran, ?Lamictal

Cost Drug interactions/potential for future problems Non-epileptic indications for AEDs
Pain: Neurontin, Topamax, Tegretol, Trileptal, Lyrica, others Headaches: Depakote, Topamax, others Psychiatric: Neurontin, Depakote, Tegretol, Lamictal, Lyrica, others

Concurrent 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