Antiepileptic Drugs

1. Antiepileptic Drugs By: DR Mehran Homam

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

4. “Older” AEDs Phenobarbital 1912 Dilantin (phenytoin) 1938 Mysoline (primidone) 1952 Zarontin (ethosuximide) 1960 Tegretol (carbamazepine) 1974 • 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. 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. 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

15. tiagabine (Gabitril) ADVANTAGES • 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. 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)

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