Phenobarbital for Febrile Seizures — Effects on Intelligence and on Seizure Recurrence

Abstract

Phenobarbital is widely used in the treatment of children with febrile seizures, although there is concern about possible behavioral and cognitive side effects. In 217 children between 8 and 36 months of age who had had at least one febrile seizure and were at heightened risk of further seizures, we compared the intelligence quotients (IQs) of a group randomly assigned to daily doses of phenobarbital (4 to 5 mg per kilogram of body weight per day) with the IQs of a group randomly assigned to placebo. After two years, the mean IQ was 7.03 [corrected] points lower in the group assigned to phenobarbital than in the placebo group (95 percent confidence interval, -11.52 to -2.5, P = 0.0068 [corrected]). Six months later, after the medication had been tapered and discontinued, the mean IQ was 5.2 points lower in the group assigned to phenobarbital (95 percent confidence interval, -10.5 to 0.04, P = 0.052). The proportion of children remaining free of subsequent seizures did not differ significantly between the treatment groups. We conclude that phenobarbital depresses cognitive performance in children treated for febrile seizures and that this disadvantage, which may outlast the administration of the drug by several months, is not offset by the benefit of seizure prevention.

Cognitive Effects of “Older” Anticonvulsants in Children with Epilepsy: A Review and Critique of the Literature

“…15 The one well-designed study that examined intellectual functioning after an extended period of phenobarbital administration found no acute effects of phenobarbital but did find substantial cognitive effects at 24 and 30 month follow-up testing. 17 Thus, the results of these investigations of phenobarbital monotherapy indicate that chronic administration of this anticonvulsant may have a deleterious effect on IQ that remits within years of treatment cessation. Some evidence of visualmotor and memory dysfunction is also indicated.…”

“…17 The 217 children ages 8 to 36 months involved in this double-blind, placebo-controlled study were randomly assigned to treatment or control groups. All children included in the study had experienced one or more febrile seizures.…”

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

“…Long-term cognitive effects of early postnatal phenobarbital exposure have been investigated in a randomized, placebo-controlled, blinded study [61] in which 217 toddler-aged children with febrile seizures were randomized to receive either phenobarbital 4-5 mg/kg/day or placebo. At age 7, several years after discontinuation of phenobarbital, 64% of these children were examined with the Wide Range Achievement Test (WRAT-R) and the Stanford-Binet Intelligence Scale [62].…”

Pharmacotherapy in pediatric epilepsy: from trial and error to rational drug and dose selection – a long way to go

“…Such an apparent efficacy, which is wrongly attributed to the drug, could be relevant across many types of epilepsy and result in AEDs being used more often than necessary, especially in the case of the developing brain of a newborn infant. This is particularly worrying if one takes into account the effect of AEDs on cognitive development and growth [49][50][51][52][53].…”