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

Abstract

Cognitive decline in children with seizure disorders is due to several factors, one being the choice of anticonvulsant and total anticonvulsant exposure. This paper reviews research investigating cognitive effects associated with "older" anticonvulsant medications (i.e., phenobarbital, phenytoin, carbamazepine, and valproate) prescribed as monotherapy. A number of cognitive difficulties such as intellectual decline, mild memory loss, visual-motor impairment, and psychomotor slowing have been associated with these medications. Each study included in this review is assessed in terms of the appropriateness of study design and ability of the reader to draw clear conclusions about the cognitive effects associated with the anticonvulsant under investigation. The review also includes a synopsis of the myriad of methodological difficulties that plague this body of literature. Conclusions that can be drawn from the existing literature are delineated, and future directions for research are suggested.

Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures

“…( 34 , 35 ) However, studies in pediatric populations showed significant impairments related to PB exposure after birth on various measures of development and with widely varying lengths of follow-up. ( 36 ) Our results support the association between PB exposure and occurrence of major motor and cognitive impairments in early childhood. Also, because the oral PB given to infants is mixed in an alcohol base, it is possible that some of the negative effects observed on neurodevelopment could be due to a very low cumulative exposure not present in infants treated with LEV.…”

Short Term Neurodevelopmental Outcome of Asphyxiated Term Neonates with Maintenance Phenobarbitone Therapy; Preliminary Findings of Ongoing Study in A Tertiary Care Hospital of Bangladesh

“…On a variety of developmental parameters and over a wide range of follow-up durations, studies in pediatric populations demonstrated significant deficits owing to PB exposure after birth. 13 We assessed all developmental domains. Few studies on pediatric neurology, particularly the effect of long term PB on cognitive function have been conducted globallyas it clearly evidences.…”

Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

“…According to the Guidelines on Neonatal Seizures, published in 2011, the first choice of treatment for neonatal seizures remains PB [5–7], even though PB is effective in less than 50% of cases [8–10]. Moreover, PB is associated with several side effects, among them, its negative effect on psychomotor development and neurological outcomes [11, 12]. For these reasons, therapeutical alternatives for neonatal seizures have been explored.…”