Antiepileptic Drugs: Pediatrics

Abstract

Abstract 1 Celestina Arrigo, 2 Patricia Grossman, and 3 Sylvie Di Nicola ( 1 Global Health Outcomes Research, UCB Pharma, Brussles, Belgium ; 2 Global Health Outcomes Research, UCB Pharma, Smyrna, GA ; and 3 Ariane II, Transiciel, Brussels, Belgium ) Rationale: Behavioral and psychiatric events are common in children with epilepsy. Some antiepileptic drugs (AEDs) may amplify these events, influencing medication selection. This investigation documents the occurrence of ADHD, behavioral disorders, psychosis, depression and anxiety in children ages 4–11 prior to- and after- initiation of a second generation AED. Methods: A retrospective cohort study was conducted amongst patients diagnosed with generalized or partial epilepsy using a U.S. claims database (July 2001 - December 2003). Patients newly started on levetiracetam (LEV), gabapentin (GBP), lamotrigine (LTG) or topiramate (TPM) as adjunctive or monotherapy were selected. GBP, LTG and TPM patients were matched separately to LEV patients with similar characteristics. Targeted behavioral and psychiatric events were identified using the International Classification of Diseases (ICD-9). Percentages of children experiencing such events were computed using claims during 6 months prior treatment initiation and during 3 months to one year of treatment. Comparisons of percentages prior to- and after- initiation of AED (i.e., within groups) were performed by means of McNemar tests. Results: Of 4030 patients included in the study, 433 were children aged 4 to 11 years old: 51.7% boys, mean age 7.7 years, 71.8% adjunctive therapy, 72.7% generalized seizures, mean duration of follow-up after AED initiation: 308 days. Numbers of children per group were: LEV-GBP: 64–61; LEV-LTG: 113–132; LEV-TPM: 121–109. Patient characteristics were similar in all groups. Mean daily doses (mg/day) over the follow-up period were: LEV-GBP: 877–1189; LEV-LTG: 884–139; LEV-TPM: 872–119. Overall prevalence was highest for behavioral disorders (between 9.2% and 18.3% among groups), ADHD (5.5%-14.4%) and psychosis (4.5%-12.8%) both prior and after AED initiation. Percentages for depression and anxiety were low (0%-6.6%). After initiation of the new AED, significant increases in percentages were found in children starting LTG for psychosis (LTG prior and after initiation percentages: 4.5%-9.1%, p = 0.034; LEV: 5.3%-8.8%, ns) and in children initiating TPM for ADHD (TPM: 5.5%-12.8%, p = 0.011; LEV: 9.1%-10.7%, ns), behavioral disorders (TPM: 9.2%-18.3%, p = 0.008; LEV: 14.9%-13.2%, ns) and psychosis (TPM: 8.3%-12.8%, p = 0.025; LEV: 7.4%-8.3%, ns). Percentages of children with behavioral disorders were systematically lower after initiation of LEV (between 10.6% and 12.5%) as compared to pre-treatment (14.2%-17.2%). Conclusions: Significant higher percentages of children with psychosis were observed compared to pre-treatment after initiating LTG and TPM. Percentages for ADHD and behavioral disorders were significantly higher in children starting TPM. Fewer children with behavioral disorders were observed after initiating LEV. (Supported by UCB Pharma S.A.)