In choosing an antiepileptic drug, not only efficacy but also potential adverse effects have to be considered. Adverse effects that have to be taken into account include acute and chronic systemic toxicity, cognitive side effects, and teratogenesis. Acute toxicity may be dose-related, allergic or an idiosyncratic reaction. Chronic toxicity may involve the nervous system or other organs. In determining the role of new antiepileptic drugs such as lamotrigine, vigabatrin, felbamate, and gabapentin a proper evaluation of both efficacy and adverse effects is required.

Acute and chronic toxicity complicates all antiepileptic medications (AED) and is idiosyncratic. Acute toxicity can be categorized into 1) acute brain dysfunction or 2) acute organ dysfunction when AED’s are started. Despite promising in vitro lymphocyte testing, anticipation of acute reactions cannot be offered. Furthermore, screening for AED toxicity by routine blood and urine tests in asymptomatic patients is of doubtful value and should be abandoned. Patients should be informed of possible reactions and immediately report early symptoms. Treatment for acute reactions is largely unstudied. It is unclear how to reintroduce AED’s following acute reactions. Often patients are sensitive to drugs with a similar chemical structure. The “desensitization” protocol of Purvis may be of merit. Three major chronic toxicities of AED’s have been noted – soft tissue and gum hypertrophy, progressive ataxia, and peripheral neuropathy. New AED’s require careful post-marketing surveillance since long term toxicity data are not yet available.

All of the established antiepileptic drugs (AEDs) can produce cognitive side effects, which are increased with polypharmacy and with increasing dosage and anticonvulsant blood levels. However, cognitive side effects are usually modest for AED monotherapy with anticonvulsant blood levels within the standard therapeutic ranges. Further, these effects are offset in part by reduced seizure activity. Controversy exists regarding possible differential cognitive effects of AEDs. A large portion of the literature examining the comparative cognitive effects of AEDs is limited by inadequate study designs. When these design flaws are considered, there is no convincing evidence of clinically significant differences in cognitive side effects of AEDs except possibly for bromide, phenobarbital and benzodiazepines. The role of cognitive side effects should be kept in proper perspective when choosing AED therapy. The cognitive side effects of anticonvulsant drugs may be overt but many times are rather subtle. It is important though to be able to recognize these effects and to put them into perspective as to how they affect our patients.

No new antiepileptic drugs (AEDs) were licensed in the United States from 1978 to 1992. In late 1992, felbamate and gabapentin were recommended for approval, and in early 1993, lamotrigine. In July 1993, felbamate was licensed, and gabapentin and lamotrigine may soon follow. Lamotrigine, vigabatrin and clobazam are in use outside the US. Tiagabine, oxcarbazepine, fosphenytoin, topiramate, vigabatrin and zonisamide are in Phase II clinical testing in the US. All of the new AEDs are effective against partial and tonic-clonic seizures. Few controlled clinical trials have been done in patients with absence and myoclonic seizures. Mechanisms of action of the new drugs have not been clearly defined. The new AEDs will provide an opportunity to improve the care of epileptic patients. Even with optimal management with currently available drugs, some 30% of patients remain refractory to medical management.