Neuropsychological and Behavioral Effects of Antiepilepsy Drugs

Loring, David W.; Marino, Susan E.; Meador, Kimford J.

doi:10.1007/s11065-007-9043-9

Cited by 191 publications

(142 citation statements)

References 120 publications

(123 reference statements)

Supporting

Mentioning

136

Contrasting

Unclassified

Order By: Relevance

“…Prior studies have shown that AEDs in and of themselves affect cognition. 32,33 In the current study, valproic acid affected attention more than either lamotrigine or ethosuximide. This highlights the importance of considering both cognitive and seizure outcome when evaluating optimal initial therapy.…”

Section: Statistical Analysis Baseline Neurocognitive Test Results Amentioning

confidence: 51%

Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

et al. 2013

View full text Add to dashboard Cite

Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine shortterm differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine.Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16-20 visit.Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16-20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p 5 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p , 0.0001). Conclusions:Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted.

show abstract

Section: Statistical Analysis Baseline Neurocognitive Test Results Amentioning

confidence: 51%

Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

et al. 2013

View full text Add to dashboard Cite

show abstract

“…However, some AEDs are endowed with unfavourable safety profiles, such as hepatotoxicity, toxicity to central nervous system (CNS) and show complex drug/drug interactions (Johannessen Landmark and Patsalos, 2010;Loring et al, 2007;Pennell, 2008). In recent years, pharmaceutical companies have developed new AEDs with improved safety profiles than the previously available ones.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of neurotoxic and neuroprotective pathways affected by antiepileptic drugs in cultured hippocampal neurons

Morte

Carreira

Falcão

et al. 2013

Toxicology in Vitro

View full text Add to dashboard Cite

a b s t r a c tIn this study we evaluated the neurotoxicity of eslicarbazepine acetate (ESL), and of its in vivo metabolites eslicarbazepine (S-Lic) and R-licarbazepine (R-Lic), as compared to the structurally-related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), in an in vitro model of cultured rat hippocampal neurons. The non-related antiepileptic drugs (AEDs) lamotrigine (LTG) and sodium valproate (VPA) were also studied. We assessed whether AEDs modulate pro-survival/pro-apoptotic pathways, such as extracellularregulated kinase (ERK1/2), Akt and stress activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK).We found that neither ESL nor its metabolites, CBZ or LTG, up to 0.3 mM, for 24 h of exposure, decreased cell viability. OXC was the most toxic drug decreasing cell viability in a concentration-dependent manner, leading to activation of caspase-3 and PARP cleavage. VPA caused the appearance of the apoptotic markers, but did not alter cell viability. ESL, S-Lic and OXC decreased the levels of phospho-ERK1/2 and of phospho-Akt, when compared to basal levels, whereas CBZ decreased phospho-SAPK/ JNK and phospho-Akt levels. LTG and VPA increased the phosphorylation levels of SAPK/JNK.These results suggest that ESL and its main metabolite S-Lic, as well as CBZ, LTG and VPA, are less toxic to hippocampal neurons than OXC, which was the most toxic agent.

show abstract

“…In studies of patients with epilepsy and in healthy volunteers, the distinct cognitive side effects associated with TPM have been well-described and studied. 1 No prospective dose-ranging studies of TPM's effect on cognition, however, have been performed, making it difficult to determine specific dose-related risk to neuropsychological function. Further, group studies have not characterized individual risk, but rather have relied only on group comparisons.…”

mentioning

confidence: 99%