Safety and tolerability profile of new antiepileptic drug treatment in children with epilepsy

ABSTRACT

Introduction: Treatment of pediatric epilepsy requires a careful evaluation of the safety and tolerability profile of antiepileptic drugs (AEDs) to avoid or minimize as much as possible adverse events (AEs) on various organs, hematological parameters, and growth, pubertal, motor, cognitive and behavioral development.

Areas covered: Treatment-emergent AEs (TEAEs) reported in the literature 2000–2018 regarding second- and third-generation AEDs used in the pediatric age, with exclusion of the neonatal period that exhibits specific peculiarities, have been described on the basis of their frequency, severity/tolerability, and particular association with a given AED.

Expert opinion: Somnolence/sedation and behavioral changes, like irritability and nervousness, are among the most commonly observed TEAEs associated with almost all AEDs. Lamotrigine, Gabapentin, Oxcarbazepine, and Levetiracetam appear to be the best-tolerated AEDs with a ≤2% withdrawal rate, while Tiagabine and Everolimus are discontinued in up to >20% of the patients because of intolerable TEAEs. For some AEDs, literature data are scanty to draw a high-level evidence on their safety and tolerability profile. The reasons are: insufficient population size, short duration of treatments, or lack of controlled trials. A future goal is that of identifying clearer, easier, and more homogeneous methodological strategies to facilitate AED testing in pediatric populations.

KEYWORDS:

• New antiepileptic drugs
• drug safety
• drug tolerability
• pediatric epilepsy
• adverse events
• cognition
• behavior

Article Highlights

• Monitoring of cognitive and behavioral effects of AEDs in pediatric age is of paramount importance given the potential harmful consequences on learning, future work, and quality of life.

• Somnolence/sedation and behavioral changes, like irritability and nervousness, are among the most commonly observed TEAEs associated with the majority of AEDs.

• Lamotrigine, Gabapentin, Oxcarbazepine, and Levetiracetam appear to be the best-tolerated AEDs with a ≤2% withdrawal rate.

• Literature data are often scanty to draw a high-level evidence on AEDs’ safety and tolerability profile.

• The weaknesses of the research in this field are mainly the paucity of controlled clinical trials, the heterogeneity of the patients included, the observation often derived from small populations of patients, and the lack of long-term studies.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.