Effectiveness and tolerability of antiepileptic drugs in 104 girls with Rett syndrome

Approximately 60–80% of girls with Rett Syndrome (RTT) have epilepsy, which represents one of the most severe problems clinicians have to deal with, especially when patients are 7–12 years old. The aim of this study was to analyze the antiepileptic drugs (AEDs) prescribed in RTT, and to assess their effectiveness and tolerability in different age groups from early infancy to adulthood. We included in this study 104 girls, aged 2–42 years (mean age 13.9 years): 89 had a mutation in MECP2, 5 in CDKL5, 2 in FOXG1, and the mutational status was unknown in the remaining 8. Epilepsy was present in 82 patients (79%). Mean age at epilepsy onset was 4.1 years. We divided the girls into 5 groups according to age: < 5, 5–9, 10–14, 15–19, 20 years and older. Valproic acid (VPA) was the most prescribed single therapy in young patients (< 15 years), whereas carbamazepine (CBZ) was preferred by clinicians in older patients. The most frequently adopted AED combination in the patients younger than 10 years and older than 15 was VPA and lamotrigine (LTG). Seizures in the group aged 10–14 years were the most difficult to treat, requiring a mean of three different AEDs, often used in combination and mostly including VPA. Seizures in fifteen patients (18%) were considered drug resistant. VPA was reported as the most effective AED in younger girls (in 40% of the patients aged < 5 years, in 19% of the girls aged 5–9 years), and CBZ the most effective in the patients 15 years or older. Adverse reactions did not differ from expected: agitation, drowsiness, and weight loss were the most frequently reported. In our sample, LTG was the least tolerated AED. We did not find correlations with MECP2 mutations in terms of effectiveness or adverse reactions. Conclusion: in this study we observed different effectiveness of AEDs based on age, and suggest that clinicians consider age-dependency when prescribing appropriate AEDs in the RTT population.