The Effects of Antiepileptic Drugs on Pediatric Cognition, Mood, and Behavior

Abstract

However, the secondary use of AEDs in mood and behavior disorders has increased manifold. 2 This article aims to discuss the use and effects of AEDs in pediatric mood and behavior Keywords ► antiepileptic drugs ► mood ► behavior ► cognition ► adverse effects AbstractIn the past three decades, several new antiepileptic drugs (AEDs) have been marketed across the world, although with a surprisingly modest improvement in overall seizure control. During the same period, the use of AEDs as mood stabilizing or impulse control agents has been trending upwards, due to a notable increase in comorbid mood and behavior disorders in children, and a desire to address these pharmacologically. AEDs have been frequently associated with adverse mood and behavior changes, along with neuropsychiatric effects on attention, memory, and cognition. In this review, we discuss the use and adverse effects of the first-(e.g., barbiturates, carbamazepine, ethosuximide, phenytoin, valproate), second-(e.g., clobazam, felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, pregabalin, tiagabine, topiramate, stiripentol, vigabatrin, zonisamide), and third-(e.g., brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, retigabine, rufinamide) generation AEDs in pediatric mood and behavior disorders. We also address what is currently known about the potential longterm neuropsychiatric consequences of AEDs. The distinction between the U.S. Food and Drug Administration-approved drugs versus off-label use of these drugs in the pediatric population is also examined.

Temporal Lobe Epilepsy and Psychiatric Comorbidity

“…For the most ASMs, remarkably few studies providing robust data on the psychiatric adverse effects in epileptic patients were identified. Barbiturates, Topiramate, Valproate, and Zonisamide have been reported to cause worsening attention ( 102 , 103 ). Phenobarbital, vigabatrin, zonisamide, topiramate, and levetiracetam could be associated with depression ( 102 ).…”

“…Barbiturates, Topiramate, Valproate, and Zonisamide have been reported to cause worsening attention ( 102 , 103 ). Phenobarbital, vigabatrin, zonisamide, topiramate, and levetiracetam could be associated with depression ( 102 ). When this is suspected, modification or discontinuation of the responsible drug is recommended.…”

Assessment and Management of Depression and Anxiety in Children and Adolescents with Epilepsy

“…It is prudent to consider the adverse effect profile when selecting antiepileptic drugs. Although neurobehavioural adverse effects have been reported with all antiepileptic drugs, neurobehavioural effects are less common with certain agents, such as lamotrigine or oxcarbazepine [16].…”

Molecular basis of mood and cognitive adverse events elucidated via a combination of pharmacovigilance data mining and functional enrichment analysis

“…Within the scope of drug development, the Central Nervous System (CNS) is responsible for a lower percentage of project terminations due to safety concerns at preclinical when compared to clinical stages, implicating that certain serious CNSrelated AEs are hardly predictable in the preclinical phase (Cook et al 2014). Various drug classes are capable of inducing CNS-related AEs, in particular Mood and/or Cognition AEs (MCAEs) (Afzal et al 2017). As a couple of illustrative examples, interferon-based immunotherapy has been shown to induce depression and suicidal ideation in patients with hepatitis C (Renault et al 1987), cancer (Valentine et al 1998), or multiple sclerosis (Fragoso et al 2010).…”

“…Antiepileptic drugs such as perampanel have also been associated with adverse mood changes (e.g. depression) and effects on cognition (Afzal et al 2017;Goji and Kanemoto 2019). In patients with lower urinary tract symptoms (Muderrisoglu et al 2019), muscarinic antagonists and 5-alpha-reductase inhibitors were associated with impaired cognition and depression, respectively.…”