Medical Pharmacology Topics   

New Antiepileptics

A number of new antiepileptic drugs have been introduced to clinical practice between 1993 and 2000. They are used mostly in the treatment of complex seizures, and have less pharmacokinetic problems than the traditional antiepileptics.

Felbamate is indicated for Lennox-Gastaut seizures and as an adjunct for partial seizures. A major side effect is a 100-fold increase in the incidence of aplastic anemia.

Lamotrigine inhibits voltage sensitive Na+ channels and is approved for refractory partial seizures. It mal also be effective in generalized tonic/clonic seizures. Lamotrigine has a long t1/2 and no active or toxic metabolites, but valproic acid reduces its clearance. Side effects include dizziness, ataxia and severe skin rash (life threatening if it spreads to the mucosa, more frequent in children).

Gabapentin was designed as a GABA analog that penetrates the CNS, but it resulted not to be a GABA-mimetic enhance. It may increase GABA release or decrease glutamate release. Gabapentin is approved for treatment of refractory partial seizures with or without generalization/adjunctive (?) and to treat chronic pain. It is not metabolized or significantly bound to plasma proteins. Side effects include somnolence, fatigue and dizziness.

Topiramate inhibits voltage-sensitive Na+ and Ca+2 channels, maybe others. It is approved for the treatment of refractory partial seizures and seems to also help with Lennox-Gastaut seizures. It is not significantly metabolized, nor protein bound and has a half life of 18-24 hrs. Side effects include cognitive dysfunction, parasthesias, dizziness, fatigue, anorexia, weight loss, blurred vision, and glaucoma. To reduce problems, the dose should be slowly increased from 50 to 400 mg/day over 8 weeks.

Tiagabine is a GABA reuptake blocker approved as an adjunctive for the treatment of refractory partial seizures. It is metabolized by and induces P450 enzymes and has a short t1/2 or 8 hrs before induction and 2-3 hrs after induction.

Levetiracetam works by an unknown mechanism and is approved for the treatment of partial seizures. It is rapidly absorbed orally, has a t1/2 of 6-8 hrs and is excreted mostly unchanged. Side effects include somnolence and dizziness.

Zonisamine is a Na+ and Ca2+ channel blocker approved as an adjunctive for the treatment of refractory partial seizures. It is a sulfonamide, so it is contraindicated in patients sensitive to them. Side effects include rash, aplastic anemia, heat shock, CNS problems, depression, fatigue and cardiovascular teratogenicity.

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A summary of representative antiepileptic agents and their indications for each seizure type follows (X = indicated, X = main agent used A = as adjunct):

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