Levetiracetam Tops Lamotrigine for Some Women With Epilepsy


Levetiracetam is more effective than is lamotrigine for initial monotherapy in female patients with juvenile myoclonic epilepsy (JME) but not for those with other idiopathic generalized epilepsy (IGE) syndromes, a new study has found.


  • The multicenter retrospective study included 543 mostly White women of childbearing age with IGE according to International League Against Epilepsy (ILAE) diagnostic criteria — a population facing limited access to effective treatment options because of the teratogenic concerns of valproate — who were prescribed either levetiracetam or lamotrigine as first-line antiseizure medication (ASM) and followed for a median of 60 months.

  • Of the total, 20.1% were diagnosed with absence epilepsy (most with juvenile absence epilepsy), 47.7% with JME, and 32.2% with IGE with generalized tonic-clonic seizures alone (GTCA).

  • Researchers conducted a propensity score analysis with inverse probability of treatment weighting (IPTW) to compare treatment failure (TF), defined as either ASM discontinuation in favor of another ASM due to ineffectiveness or adverse effects or the adding of a second ASM due to ineffectiveness, among patients who received levetiracetam or lamotrigine as initial monotherapy.


  • Compared with lamotrigine, levetiracetam was associated with a reduced risk for TF after adjustment for all baseline variables (IPTW-adjusted hazard ratio [HR], 0.77; 95% CI, 0.59-0.99; P = .04).

  • After stratification according to different IGE subsyndromes, the higher effectiveness of levetiracetam was confirmed only in patients with JME (IPTW-adjusted HR, 0.47; 95% CI, 0.32-0.68; P < .001), whereas there were no significant differences in absence epilepsy (IPTW-adjusted HR, 1.17; 95% CI, 0.69-1.99; P = .60) and GTCA (IPTW-adjusted HR, 1.02; 95% CI, 0.58-1.77; P = .90).

  • Levetiracetam was also associated with a higher ASM retention compared with lamotrigine among patients with JME, whereas there were no significant differences in absence epilepsy.

  • Both ASMs were well tolerated, with similar retention rates during follow-up in the entire cohort, but there was a higher number of adverse effects in the levetiracetam group, especially behavioral adverse effects, and drowsiness


The finding that TF is significantly lower in the levetiracetam group when adjusted for all confounding factors, “appeared to be mainly driven by the remarkable superiority of levetiracetam observed among female patients with JME”, wrote the authors, who stressed that levetiracetam and lamotrigine are the safest ASMs during pregnancy.


The study was carried out by Emanuele Cerulli Irelli MD, PhD, Department of Human Neurosciences, Sapienza University, Rome, Italy, and colleagues. It was published online on October 2, 2023 in JAMA Neurology.


The retrospective design implies recall bias, selection bias, and analysis bias. The heterogenous distribution of different IGE subsyndromes may have underpowered the analysis stratified per epilepsy syndrome. Relying on the records of clinical visits instead of standardized questionnaires for reporting adverse effects may have underestimated their true prevalence.


Cerulli Irelli has no relevant conflicts of interest; see paper for disclosures of other authors.

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