1. Antiepileptic Drugs

2. 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

3. Tonic-clonic (“grand mal”) Absence (“petit mal”) Myoclonic Tonic
Seizure Types
Primary Generalized
Tonic-clonic (“grand mal”)
Absence (“petit mal”)
Myoclonic
Tonic
Atonic (“drop attacks”)
Partial
simple vs. complex (“psychomotor”)

4. Also Tegretol-XR and Carbatrol now IV form and Depakote-ER
“Older” AEDs
Phenobarbital
Dilantin (phenytoin)
Mysoline (primidone)
Zarontin (ethosuximide)
Tegretol (carbamazepine)
Also Tegretol-XR and Carbatrol
Depakote, Depakene (valproate) 1978
now IV form and Depakote-ER

5. 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

6. 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

7. First line for partial seizures for years Once a day IV form
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

8. 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

9. Barbiturates (primidone [Mysoline] and phenobarbital)
Effective Once a day (phenobarbital) cheap IV form (phenobarbital)
Sedation and cognitive effects Withdrawal

10. Other old medications
acetazolamide (Diamox) clonazepam (Klonopin) & lorazepam (Ativan) ethosuximide (Zarontin) ketogenic diet ACTH/steroids

11. 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

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

13. 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)

14. ADVANTAGES DISADVANTAGES topiramate (Topamax)
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

15. ADVANTAGES DISADVANTAGES tiagabine (Gabitril)
Minimal effect on other medications
DISADVANTAGES
Dose is dependent on concurrent AEDs
Anxiety
Occasionally makes some seizure types worse

16. 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

17. 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

18. 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

19. 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

20. 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

21. Risk of weight gain “Risk” of weight loss Weight Issues
Depakote (valproate)
Neurontin (gabapentin) and Lyrica (pregabalin)
Less so
“Risk” of weight loss
Topamax (topiramate)
Zonegran (zonisamide)
Felbatol (felbamate)

22. Drugs that decrease efficacy of oral contraceptives
Dilantin (phenytoin) Tegretol, Carbatrol (carbamazepine) Phenobarbital Mysoline (primidone) Topamax (topiramate) at higher doses Trileptal (oxcarbazepine)

23. 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