Behavioral and Cognitive Effects of Anticonvulsant Therapy

Abstract

In 1985, the Committee on Drugs reviewed evidence, primarily from adult studies, indicating that anticonvulsant therapy may have detrimental effects on behavior and cognition.1 It was recommended that pediatricians judiciously review indications for the use of antiepileptic medications, weigh the efficacy versus the side effects of specific drugs, and be alert to reported changes in patient behavior, mood, or cognitive function. Furthermore, the Committee noted the need for the development of brief neuro-psychologic screening tests to identify subtle intellectual and behavioral side effects as well as the need for the delineation of behavioral and cognitive effects of specific antiepileptic medications in children. This commentary presents an overview of current pediatric studies of antiepileptic drugs and cognitive/behavioral function. Behavioral Effects Behavioral disturbances, reported in 20% to 30% of children with epilepsy,2 are frequently unrelated to the anticonvulsant drug regimen, but may result from disordered cerebral function or occur as a secondary reaction to the illness.3 Some children with seizures differ behaviorally from healthy controls both before the initiation of treatment and after its cessation. Behavioral differences are most prominent with absence and partial seizures.4 The most comprehensive incidence data on the behavioral side effects of antiepileptic drugs derive from a study of 392 children receiving long-term monotherapy with phenobarbital, primidone, phenytoin, carbamazepine, on valprnoate for treatment of epilepsy on febrile convulsions.5 As shown in the Table, behavioral effects were most commonly reported in patients treated with phenobarbital, and were relatively uncommon in children treated with primidone, phenytoin, on valproate. Drowsiness and longer sleep were associated with higher plasma levels of phenobarbital, whereas signs of excitation tended to occur at lower dosages and resolved when higher on stable plasma levels were achieved.