Among girls and women of reproductive age with juvenile myoclonic epilepsy, levetiracetam is more effective than lamotrigine as an initial monotherapy.

Levetiracetam may be an alternative initial monotherapy for girls and women of reproductive age with juvenile myoclonic epilepsy (JME), but not for those with idiopathic generalized epilepsy (IGE), according to study findings published in JAMA Neurology.

IGE is a common form of epilepsy that has traditionally been treated with valproate. The use of valproate, however, is not recommended for women of reproductive age due to the risk for major congenital malformations and neurodevelopmental disorders.

For the study, researchers sought to evaluate whether levetiracetam or lamotrigine may be an alternative therapeutic option. The researchers sourced data for this comparative effectiveness cohort study from a population of patients who attended 22 epilepsy centers between 1994 and 2022. Girls or women aged 10 to 50 with IGE who used levetiracetam or lamotrigine  were evaluated for treatment failure. Treatment failure was defined as medication discontinuation due to ineffectiveness or adverse effects or the addition of a second medication due to ineffectiveness. To balance for cohort differences, an inverse probability of treatment weighting approach was used.

Our data suggest the use of levetiracetam as initial alternative monotherapy in patients with JME …

The levetiracetam and lamotrigine cohorts comprised girls or women who were:

  • mean age, 17 and 17,
  • 31.7% and 35.1% had a family history of seizure,
  • 9.6% and 7.4% had a history of febrile seizures,
  • 11.9% and 16.9% had a psychiatric comorbidity, and
  • 3.2% and 4.3% had a mild intellectual disability, respectively.

The IGE etiology differed significantly between medication cohorts, in which more levetiracetam users had JME (51.9% vs 42%) or epilepsy with generalized tonic-clonic seizures (32.7% vs 31.6%) and fewer had absence epilepsy (15.4% vs 26.4%) compared with lamotrigine users, respectively.

The average initial maintenance dose was 219 mg for levetiracetam and 1197 mg lamotrigine.

Overall, 238 treatment failure events occurred, in which more failures occurred among lamotrigine users compared with levetiracetam users. In the multivariate analysis, compared with lamotrigine, levetiracetam was associated with decreased risk for treatment failure.

Stratified by IGE etiology, compared with lamotrigine, levetiracetam was associated with a decreased risk for treatment failure among patients with JME but not among patients with absence seizure  or generalized tonic-clonic seizures.

In a sensitivity analysis, levetiracetam was associated with increased odds of freedom from seizures at 12 months and was less likely to be associated with myoclonic seizure worsening compared with lamotrigine, respectively.

The rate of adverse effects was higher among patient who received levetiracetam compared with those who received lamotrigine.

The limitations of this study included its retrospective design and the heterogeneous distribution across the IGE subsyndromes.

The researchers concluded, “Our data suggest the use of levetiracetam as initial alternative monotherapy in patients with JME, whereas further studies are warranted to investigate the comparative effectiveness and safety of VPA [valproate] alternatives in IGE syndromes other than JME in female patients of childbearing age.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Source:, Jessica Nye, PhD