Antiepileptic drugs (AEDs) may aggravate pre-existing
seizures and trigger new seizure types. However, the extent and mechanisms of this problem are unclear, for several reasons. AED trials are not designed to detect worsening of
seizures, severe childhood
epilepsies may fluctuate in severity, and worsening of
seizures may be over-hastily ascribed to the introduction of a new AED. Moreover, the seizure and the
epilepsy type may have been incorrectly diagnosed. The problem is identification of true aggravation of
epilepsy in the absence of overdosage or toxicity. This is a common and clinically important problem that concerns both established and newer AEDs, but the
biologic mechanisms involved are unknown. An increase in seizure frequency due to overdosage has been reported with
phenytoin but is rare with other AEDs. Paradoxical reaction has been reported with
carbamazepine (CBZ),
benzodiazepines, and
vigabatrin (VGB). Exacerbation of
seizures may also occur during AED-induced
encephalopathy or hepatopathy. An inappropriate choice of the AED (i.e., a purely pharmacodynamic mechanism) can induce worsening when CBZ or VGB is used in absence and
myoclonic seizures. Further research should determine whether seizure exacerbation is associated with the type of
epilepsy or with the type of EEG abnormality. Recent evidence indicates that
lamotrigine is inappropriate in severe
myoclonic epilepsy. Some childhood epileptic
encephalopathies have been affected by certain seizure-worsening mechanisms. Whether this is due to a predisposition in specific syndromes or to an increased risk for adverse effects in patients undergoing multiple AED manipulations is unclear. Furthermore, some syndromes are not the sum of accompanying seizure types but have unique neurobiology.