Transcript New Antiepileptic Drugs

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)
1912
1938
1952
1960
1974
– Also Tegretol-XR and Carbatrol
Depakote, 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)
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