Psychiatric and behavioral concerns of perampanel with concomitant levetiracetam in children with epilepsy

Epilepsy Behav. 2024 May:154:109740. doi: 10.1016/j.yebeh.2024.109740. Epub 2024 Mar 27.

Abstract

Purpose: Perampanel (PER) is expanding the therapeutic scope for pediatric epilepsy owing to its efficacy and favorable safety profile. However, concerns about psychiatric and behavioral adverse events (PBAEs) in combination therapy with levetiracetam (LEV) continue to contribute to hesitation in its prescription. We investigated the risk profiles for PBAEs when adding PER to pediatric epilepsy treatment and analyzed the differences according to the presence of concomitant LEV.

Methods: We retrospectively reviewed the medical records of children aged 4-18 years with epilepsy who were prescribed PER as adjunctive therapy from March 2016 to February 2023. We compared the occurrence and management of PBAEs between the PER without LEV and PER with LEV groups. The risk factors for PBAEs were also analyzed.

Results: Ninety-four patients (53 boys and 41 girls) were included in this study. The median age of total patients at the time of adding PER was 14.9 years (12.3-16.4 years), and 53 patients (56.4 %) had concomitant LEV. Forty-seven PBAEs occurred in 34 patients (36.2 %), with no significant differences depending on whether concomitant LEV is present or not. The most common PBAEs were aggression (14.9 %), irritability (9.6 %), affect lability (7.4 %), and acute psychosis (6.4 %). PBAEs occurred at a lower dosage (2-6 mg/day) in 70.6 % of the patients. In addition, 73.5 % of patients with PBAEs continued PER treatment by follow-up observation or by reducing the PER dosage. No risk factors, such as the presence of concomitant LEV or lamotrigine, any comorbid conditions, higher PER dosage (8-12 mg/day), two or more concomitant anti-seizure medications, and younger age (<13 years) at PER add-on, showed significant associations.

Conclusion: When expanding the use of anti-seizure medications in pediatric patients, real-world evidence on safety issues is crucial for pediatric epileptologists. We confirmed that combination therapy with PER and LEV did not increase the risk profile of PBAEs.

Keywords: Adverse events; Epilepsy; Levetiracetam; Perampanel; Risk factors.

MeSH terms

  • Adolescent
  • Anticonvulsants* / administration & dosage
  • Anticonvulsants* / adverse effects
  • Anticonvulsants* / therapeutic use
  • Child
  • Child, Preschool
  • Drug Therapy, Combination*
  • Epilepsy* / complications
  • Epilepsy* / drug therapy
  • Epilepsy* / psychology
  • Female
  • Humans
  • Levetiracetam* / administration & dosage
  • Levetiracetam* / adverse effects
  • Levetiracetam* / therapeutic use
  • Male
  • Mental Disorders* / complications
  • Mental Disorders* / drug therapy
  • Mental Disorders* / epidemiology
  • Nitriles* / therapeutic use
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Retrospective Studies

Substances

  • perampanel
  • Levetiracetam
  • Anticonvulsants
  • Pyridones
  • Nitriles