Early life exposure to antiepileptic drugs may cause cognitive deficits in newborns

In a study published in the  Annals of Neurology, researchers at Georgetown University Medical Center (GUMC) report that the anti-epilepsy drug phenobarbital given to rat pups about a week old changed the way the animals' brains were wired, causing cognitive abnormalities later in life. The results provide the first evidence that exposure to antiepileptic drugs during a sensitive postnatal period impairs physiological maturation of synapses in neurons that survive the initial drug insult.

Using patch-clamp recordings to examine functional synaptic maturation in striatal medium spiny neurons from neonatal rats exposed to antiepileptic drugs with proapoptotic action (phenobarbital, phenytoin, lamotrigine) and without proapoptotic action (levetiracetam). Phenobarbital-exposed rats were also assessed for reversal learning at weaning.

Synaptic maturation was absent in rats exposed at P7 to a single dose of phenobarbital, phenytoin, or lamotrigine, but not levetiracetam. Interestingly melatonin pretreatment which prevents drug induced neurodevelopmental apoptosis, prevented this disruption in maturation.

The study raises new questions about using phenobarbitone as  the first-line drug to treat epilepsy in neonates.

Citation: Forcelli, P. A., Janssen, M. J., Vicini, S. and Gale, K. (2012), Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Ann Neurol.. doi: 10.1002/ana.23600 [abstract]