Paradoxical effects of levetiracetam in people with epilepsy with rhythmic epileptiform discharges

Epilepsy Behav. 2023 Jun:143:109225. doi: 10.1016/j.yebeh.2023.109225. Epub 2023 Apr 30.

Abstract

Objective: To elucidate the incidence and risk factors for paradoxical effects (i.e., increased seizure frequency, increased seizure severity, or onset of new seizure types) of levetiracetam (LEV) in people with epilepsy (PWE) and identify the usefulness of electroencephalography (EEG) in predicting these effects.

Methods: We examined data for consecutive PWE treated with LEV. All PWE underwent EEG and magnetic resonance imaging (MRI) before LEV administration. We also evaluated the incidence of paradoxical LEV effects and conducted multivariate logistic regression analyses to identify the associated factors.

Results: In total, 210 (66.2%) of 317 PWEs treated in our department had a history of LEV use. The incidence of paradoxical LEV effects was 5.2% (n = 11) and was significantly associated with a high LEV dose (p = 0.029), high seizure frequency (p = 0.005), temporal lobe epilepsy (p = 0.004), focal awareness seizure (p = 0.004), focal impaired awareness seizure (p = 0.007), spike (p = 0.015), rhythmic epileptiform discharges (REDs; p = 0.003), and MRI-identified focal cortical dysplasia (FCD; p < 0.0001). Multivariate analyses revealed that REDs (odds ratio [OR] = 5.35, p = 0.048, 95% confidence interval [CI]: 1.01-28.21) were independently associated with paradoxical LEV effects.

Conclusions: Paradoxical LEV effects occurred in PWE, particularly in those with drug-resistant focal epilepsy. Furthermore, the occurrence of REDs in EEG was an independent factor associated with the paradoxical effects of LEV in PWE.

Keywords: Anti-seizure medication; Electroencephalography; Focal cortical dysplasia; Seizure worsening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticonvulsants / adverse effects
  • Drug Resistant Epilepsy* / drug therapy
  • Electroencephalography
  • Epilepsies, Partial* / drug therapy
  • Epilepsy* / chemically induced
  • Epilepsy* / complications
  • Epilepsy* / drug therapy
  • Humans
  • Levetiracetam / adverse effects
  • Seizures / chemically induced
  • Seizures / drug therapy
  • Treatment Outcome

Substances

  • Levetiracetam
  • Anticonvulsants