Late Cognitive Effects of Early Treatment with Phenobarbital

Abstract

We previously reported that IQ was significantly lowered in a group of toddler-aged children randomly assigned to receive phenobarbital or placebo for febrile seizures and there was no difference in the febrile seizure recurrence rate. We retested these children 3-5 years later, after they had entered school, to determine whether those effects persisted over the longer term and whether later school performance might be affected. On follow-up testing of 139 (of the original n = 217) Western Washington children who had experienced febrile seizures, we found that the phenobarbital group scored significantly lower than the placebo group on the Wide Range Achievement Test (WRAT-R) reading achievement standard score (87.6 vs 95.6; p = 0.007). There was a nonsignificant mean difference of 3.71 IQ points on the Stanford-Binet, with the phenobarbital-treated group scoring lower (102.2 vs 105.7; p = 0.09). There were five children in our sample with afebrile seizures during the 5-year period after the end of the medication trial. Two had been assigned to phenobarbital, and three had been in the placebo group. We conclude there may be a long-term adverse cognitive effect of phenobarbital on the developmental skills (language/verbal) being acquired during the period of treatment and no beneficial effect on the rate of febrile seizure recurrences or later nonfebrile seizures.

Safety and Tolerability of Antiepileptic Drug Treatment in Children with Epilepsy

“…[124] Clear evidence has been obtained about the reduction of intelligence quotient scores and increased P300 wave latency, an electrophysiological marker of reduced speed in cognitive processing, in children treated with PB. [125] The long-term cognitive effects of newer AEDs in children are largely unknown. [6] Few well designed studies have systematically investigated the cognitive effects of newer AEDs in children and adolescents in the short term.…”

Cognitive/behavioral teratogenetic effects of antiepileptic drugs

“…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]. Phenobarbital-exposed children had significantly impaired performance in WRAT-R reading scores, but not in the Stanford-Binet Scale, compared with the placebo group.…”

Possíveis interfaces entre TDAH e epilepsia

“…Após a interrupção do fenobarbital, foi observado, por meio da realização de testes neuropsicológicos, que houve aumento significativo nos escores de QI com importante melhora no desempenho de itens não verbais, tendo demonstrado também efeitos deletérios nos testes que envolvem maior demanda da atenção nos pacientes que continuaram em uso da droga. O impacto negativo do uso do fenobarbital sob o desempenho cognitivo foi confirmado por outros autores 58 . Apesar de os barbitúricos apresentarem propriedades sedativas em adultos, em crianças essa droga pode cursar com alterações comportamentais importantes, como induzir ao surgimento de sintomas de hiperatividade, irritabilidade, além de sintomas depressivos 58,59 .…”

“…O impacto negativo do uso do fenobarbital sob o desempenho cognitivo foi confirmado por outros autores 58 . Apesar de os barbitúricos apresentarem propriedades sedativas em adultos, em crianças essa droga pode cursar com alterações comportamentais importantes, como induzir ao surgimento de sintomas de hiperatividade, irritabilidade, além de sintomas depressivos 58,59 . Em estudos em voluntá-rios saudáveis, benzodiazepínicos e barbitúricos produziram efeitos adversos cognitivos moderados, especialmente se comparados com os efeitos da carbamazepina e da fenitoína, drogas que interferem pouco no desempenho cognitivo 60,61 .…”