Abstracts

RATIONALE: We have previously reported on the excellent efficacy of levetiracetam (LEV) in children with intractable epilepsy ( Neurology 2001;56 (Suppl 3): A46). Our preliminary observation of behavioral adverse experiences, led us to retrospectively review the behavioral profile in 79 children with seizures treated with LEV as add-on therapy.
METHODS: We queried our clinical database (Filemaker) for all children treated with LEV at our institution over an 18 month period. A total of 79 children were identified (41 male; 38 female) with a mean age of 11 years (2-20 yrs.). LEV was titrated to a maximum dose on a clinical basis. The average dose was 39.5 mg/kg/d (20-60 mg/kg/d). 77 children were on concomitant anti-epileptic drugs (AEDs). Office visits and phone records were reviewed to tabulate adverse experiences. Behavioral side effects were rated as mild, moderate or severe by a single investigator.
RESULTS: In 23 of 79 (30%) children behavioral side effects were reported ranging from mild to severe. In these 23 children behavioral symptoms included: irritability/agitation 15; aggression 9; altered mood 7; inattention/hyperactivity 5; anxiety/panic 2; hallucinations 1. One child had exacerbation of a previously established obsessive-compulsive disorder (OCD). Of 18 children who discontinued LEV, 9 (12%) did so due to severe behavioral symptoms. In 5 of these 9 children, parents opted to discontinue LEV despite good efficacy (seizure reduction [gt] 50%).
CONCLUSIONS: Levetiracetam, like most other AEDs, induces central nervous system related side effects that are usually mild and transient. However, in our cohort of 79 children, we report adverse behavioral experiences in 23 (30%) which led to discontinuation of the LEV in 9 (12%) children. This incidence of these behavioral effects appears to be more frequent than those reported in the adult phase III levetiracetam clinical trials. These findings may be due to our relatively rapid rate of titration , pre-morbid behavioral substrate in predominately intractable epilepsy patients and polypharmacy. On-going randomized placebo controlled clinical trials of levetiracetam in children may clarify these unique issues in the pediatric population.