A recent study evaluated the effectiveness and safety of substitution monotherapy vs add-on therapy as second-line treatment options in women aged 10 to 50 years with idiopathic generalized epilepsy following the failure of first-line antiseizure medications other than valproic acid. 

In the multicenter, retrospective, comparative effectiveness cohort study, published in JAMA Network Open, researchers included 249 women diagnosed with idiopathic generalized epilepsy (IGE) across 18 epilepsy centers in four countries, analyzing data from 1995 to 2023.

The researchers found no statistically significant differences in treatment failure rates between the two strategies, with 32.9% of patients receiving add-on therapy and 35.0% using substitution monotherapy experiencing treatment failure (IPTW-adjusted hazard ratio [HR] = 0.89, P = .69). Discontinuation rates as a result of ineffectiveness or adverse effects were also similar, with 24.7% in the add-on group and 28.2% in the substitution group (IPTW-adjusted HR = 0.97, P = .92).

Among non–valproic acid add-on regimens, the combination of levetiracetam and lamotrigine showed a lower risk of treatment failure compared with other combinations, with adjusted HRs of 2.41 (P = .02) and 4.03 (P = .001), respectively. However, valproic acid remained the most effective second-line antiseizure medications (ASMs).

The cohort had a median age of 18 years, with 58.6% receiving an add-on regimen and 41.4% receiving substitution monotherapy. The most commonly prescribed antiseizure medications were levetiracetam (30.5%), lamotrigine (22.5%), and valproic acid (19.3%). The findings suggested that both treatment strategies are viable options among women with IGE, allowing for tailored approaches based on individual patient characteristics.

"Our findings support the use of either substitution monotherapy or add-on therapy as effective second-line options, with the choice best guided by individual patient characteristics," said Emanuele Cerulli Irelli, MD, PhD, of the Department of Human Neurosciences at Sapienza University in Italy, and colleagues.

The study emphasized the need for evidence-based treatment strategies tailored to women with IGE, particularly those who may become pregnant, as the use of valproic acid is discouraged because of its teratogenic risks.

Full disclosures are available in the study.