title: Effectiveness and tolerability of antiepileptic drugs in 104 girls with Rett syndrome.
abstract: 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 7-12years 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 2-42years (mean age 13.9years): 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 4.1years. We divided the girls into 5 groups according to age: <5, 5-9, 10-14, 15-19, 20years and older. Valproic acid (VPA) was the most prescribed single therapy in young patients (<15years), whereas carbamazepine (CBZ) was preferred by clinicians in older patients. The most frequently adopted AED combination in the patients younger than 10years and older than 15 was VPA and lamotrigine (LTG). Seizures in the group aged 10-14years 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 <5years, in 19% of the girls aged 5-9years), and CBZ the most effective in the patients 15years 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.
  
  
  
  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.
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy. Electronic address: miriam.savini@unimi.it.
authors.forename: Miriam Nella
authors.initials: MN
authors.lastname: Savini
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Maria Sonia
authors.initials: MS
authors.lastname: Nowbut
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Peron
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Katherine
authors.initials: K
authors.lastname: Turner
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: La Briola
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Health Sciences, Università degli Studi di Milano, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002220:Carbamazepine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D017063:Outcome Assessment, Health Care; D015518:Rett Syndrome / Q000150:complications / Q000188:drug therapy*; D014227:Triazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014635:Valproic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine
keywords: Age-dependency; Antiepileptic drugs; Epilepsy; Rett syndrome