What With all the New Medicines?

Reference materials

    * PDR
    * Medline
    * New Drugs: Which should be included in the formulary? Arch. Neurol. 57:272, 2000.
    * The Treatment of Epilepsy. Principles and Practice. Elaine Wyllie, editor.
    * Epilepsy. A comprehensive textbook. Engel and Pedley, editors.
    * OUHSC Epilepsy website
    * FDA's Electronic Orange Book

What do we call new?

    * Newly marketed?
    * New use for an old drug?
    * New to us but unavailable in U.S.?

Advantages to rediscovering old drugs.

    * They had to be potent to be identified as seizure medicines.
    * They are no longer protected as brand, so cheap generics are available.
    * New drugs are not more effective and have side-effects.

The following AntiEpileptics are effective and have a role in Epilepsy.
bromides  1857  Cl channel on GABA  1st line for porphyria
phenobarbital  1912  GABA receptor  1st line
ketogenic diet  1921  unknown  Lennox-Gastaut
Dilantin  1938  Blocks rapid firing, Na  1st line
Mysoline  1952  GABA  1st line
Celontin  1953  unknown  2nd line for JME
ACTH  1950s  unknown  infantile spasms
Zarontin  1960  Ca currents  1st line for absence
Tegretol  1974  Na currents  1st line
Tegretol-XR  1996   
Carbatrol  1997   
Klonopin  1975  GABA  1st line for myoclonic
Depakene  1978  GABA  1st line for JME
Depakote  1983   
Sprinkles  1989   
Depacon, i.v.  1996   
Ativan, i.v.  1982  GABA  1st line for Status
Felbatol  1993  NMDA  Lennox-Gastaut
Neurontin  1993  unknown (not GABA)  1st line for pain
Lamictal  1994  Blocks rapid firing  2nd line
Cerebyx, i.v.  1996  prodrug of Dilantin  1st line for Status
Topamax  1996  multiple actions  3rd line
Gabitril  1997  GABA  3rd line
Diastat  1997  GABA  rectal valium for Status
Trileptal  2000  unknown  2nd line
Zonegran  2000  Unknown  3rd line
Keppra  2000  Unknown  3rd line
Newly marketed for status epilepticus
Ativan  1-2 mg i.v. push, up to 4 mg
lorazepam  1st line for status
 effective
-  -
Cerebyx  20 mg PE/kg i.v., 150 mg PE/min
fosphenytoin  1st line for status
PE=phenytoin equivalent  effective
-  -
Diastat  5-20 mg, rectal depending on age and weight
diazepam  outpatient niche
 effective
-  -
Depacon  20 mg/kg i.v. diluted in 50 ml most fluids, infused over 1 hr
valproic acid  Not effective for status
 npo patient niche
Newly marketed for Infantile Spasms
Zonegran  200 mg b.i.d.
zonisamide  available in Japan, Korea, US
 ? efficacy
-  -
Sabril  100 mg/kg
vigabatrin  1st line
 effective
 used worldwide except in U.S. because of
 visual field constriction due to retinal damage and
 reports of brain white matter damage in animals
-  -
nitrazepam  1 mg/kg
 2nd line
 effective
 used worldwide except in U.S.
Newly marketed for Lennox-Gastaut
ketogenic  1990's saw a resurgence of enthusiasm
diet  best in young patients
 moderately effective
-  -
Felbatol  1200 mg t.i.d.
felbamate  APLASTIC_ANEMIA HEPATIC_FAILURE
 effective
-  -
Lamictal  300 mg b.i.d.
lamotrigine  titrate slow
 not effective, causes myoclonus
-  -
clobazam  30 mg
 used worldwide except in U.S.
 moderately effective
Newly marketed for partial seizures
Neurontin  900 mg t.i.d.
gabapentin  3rd line
 ineffective against convulsions
 1st line for neuropathic pain
-  -
Lamictal  300 mg b.i.d.
lamotrigine  best 2nd line
 titrate slow, 25 qweek
-  -
Topamax  200 mg t.i.d.
topiramate  3rd line, kidney stones
 titrate slow, 50 qweek
-  -
Gabitril  20 mg t.i.d.
tiagabine  3rd line
 titrate slow, 4 mg qweek
-  -
Trileptal  1200 mg b.i.d.
oxcarbazepine  2nd line
 SIADH like Tegretol
-  -
Zonegran  300 mg b.i.d.
zonisamide  3rd line
 Kidney stones, Rash
Keppra  2000 mg b.i.d.
levetiracetam  3rd line