While severe and even sometimes life threatening, idiosyncratic reactions are rare and unpredictable. Idiosyncratic reactions arise with every one of the older AEDs and with Felbamate, and include bone marrow suppression, allergic reactions and gastrointestinal effects.
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New AEDs are needed because existing agents are not completely efficacious or tolerated, especially for patients with partial onset seizures. There has been great progress in new drug development. Newly approved AEDs include gabapentin, lamotrigine, and topiramate. These agents offer advantages over the older AEDs in terms of better tolerability, ease of use and, in some cases, broader efficacy.
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Gabapentin (Neurontin) was developed as a structural analog to GABA but appears to display very few GABAergic effects. The mechanism of action has not been established. Gabapentin is effective as add-on therapy and also probably as monotherapy for partial and secondarily generalized tonic seizures at doses ranging from 1200-mg day to 4800 mg per day. Gabapentin is not effective for typical absence seizures. The medication is well tolerated with adverse effects principally being somnolence and fatigue that lessens with continued therapy. Lack of drug interactions is one pharmacological advantage of Gabapentin. Less than 3% of the medication is protein bound and elimination is primarily renal. There are no active metabolites.
Lamotrigine (Lamictal online) is a triazine derivative structurally and pharmacologically unrelated to currently used AEDs. The mechanism of action in unknown, although the drug may have an effect on voltage sensitive calcium channels, thus preventing the release of excitatory neurotransmitters. Lamotrigine shows efficacy as adjunctive therapy and in monotherapy for partial seizures, all generalized tonic clonic seizures, and absence seizures. Adverse events include rash, dizziness, ataxia, somnolence and headache. Serious rash leading to hospitalization is more frequent with concomitant valproate. The drug reaches peak plasma concentrations at 1.4 to 4.8 hours after oral administration. Lamotrigine is 55% protein bound. More than 90% of elimination is renal. There is a linear serum dose relationship within the therapeutic range. The usual maintenance dosage is 300 to 500 mg/day in patients receiving liver enzyme inducing AEDs (carbamazepine, phenytoin, phenobarbital) and 100 to 150 rag/day in patients receiving valproate as well.
Topiramate is a carbonic anhydrase inhibitor that appears to have multiple mechanisms of action. It is effective in treating essentially all seizure types. The most common side effects include cognitive slowing. The drug displays intermediate protein binding and minimal drug interactions. The typical effective dose is 400 mg per day although some patients benefit from doses as high 1200 mg per day.
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