Efficacy of adjunctive lacosamide in children with drug-resistant epilepsy: A systematic review, meta-analysis and meta-regression

Background

To systematically evaluate the efficacy, safety, and tolerability of adjunctive lacosamide (LCM) in children and adolescents with drug-resistant epilepsy (DRE).

Methods

A systematic review and single-arm meta-analysis was conducted in accordance with PRISMA 2020 guidelines. MEDLINE, Embase, and Cochrane Library were searched up to April 2025. Observational studies including pediatric patients (<18 years) with DRE treated with adjunctive LCM were included. Pooled estimates were derived using random-effects models. Subgroup analyses assessed age (<2, 2–12, >12 years) and dose (≤6 vs >6 mg/kg/day). Meta-regression explored the impact of etiology, concomitant sodium channel blocker exposure, prior antiseizure medications, and study design. Cumulative analyses examined temporal trends in efficacy and safety.

Results

Twelve studies comprising 503 patients met inclusion criteria. Seizure freedom was achieved in 22 % (95 % CI 15–31 %). Rates of ≥50 % reduction were 61 % at 3 months, 62 % at 6 months, 58 % at 9 months, and 48 % at 12 months. Adverse events occurred in 28 % (19–37 %), most commonly drowsiness (12 %) and irritability (7 %); discontinuation reached 24 % (14–34 %). Children <2 years had lower 12-month response (17 %¦vs 57 % in 2–12 years). Lower doses (≤6 mg/kg/day) yielded higher short-term responses (68 %¦vs 38 %) but greater discontinuation and irritability. Meta-regression linked genetic etiology and sodium channel blocker exposure with improved outcomes, while higher mean dose predicted reduced 3-month response. Cumulative analyses showed stable estimates after 2020, with attenuation at 12 months.

Conclusions

Adjunctive LCM may offer meaningful seizure reduction with acceptable tolerability in pediatric DRE, though discontinuation is frequent. Age, dose, and etiology influence treatment response, highlighting the need for individualized strategies and prospective controlled trials with extended follow-up.