Abstracts

Rationale: While levetiracetam is prescribed for a broad spectrum of seizure types, it does not have a specific indication for absence epilepsy. Given the common use of this drug in clinical practice, we sought to determine the real-world efficacy of levetiracetam for the treatment of childhood and juvenile absence epilepsies (CAE and JAE). We hypothesized that levetiracetam is commonly prescribed for children with CAE or JAE and that certain electroencephalographic (EEG) findings in patients with absence epilepsies could help predict the efficacy of levetiracetam. Methods: We performed a systematic chart review of all patients evaluated and treated for new onset absence epilepsies (described in the medical record as absence seizures with diagnoses of CAE, JAE, or Genetic Generalized Epilepsy – GGE) at our tertiary care Pediatric Neurology clinic by general child neurologists or epileptologists between 1/2011 and 1/2016. We recorded relevant data including clinical semiology, epilepsy syndrome diagnosis, EEG findings, medication treatments, response to treatment, and side effects. Levetiracetam was considered effective if it was continued at the patient’s last clinic visit due to improved seizure frequency and no additional anti-seizure medication was prescribed or if levetiracetam was discontinued due to seizure freedom. Results: Among the 158 children diagnosed with absence epilepsies before 18 years of age, 72 were treated with levetiracetam. The majority of patients had a recorded diagnosis of GGE (N=46); firm diagnoses of CAE (N=11) or JAE (N=9) were inconsistently documented. Levetiracetam was discontinued in 74% of patients (N=53/72) due to either ineffectiveness (59%, N=35/53) or side effects (45%, N=24/53). The rate of discontinuation due to side effects was not different between levetiracetam and other medications (OR 0.69, CI 95% 0.36-1.31). The presence of polyspikes on the pre-treatment EEG was slightly higher in the levetiracetam effective group (44%, N=8/18) compared to the levetiracetam failed group (27%, N=14/52) (OR 0.46, CI 95% 0.15-1.40). The maximal prescribed dose was lower for children in whom levetiracetam was deemed effective (29 ± 13 mg/kg/day) compared to those for whom levetiracetam treatment failed (42 ± 20 mg/kg/day) (p= 0.005). The median treatment duration until discontinuation of levetiracetam was 8.5 months (IQR 2, 17 months). Conclusions: Based on our study results, levetiracetam is often prescribed but may have lower efficacy (26%) than recently published rates of seizure-freedom with first-line medications including ethosuximide and valproic acid (45% and 44%, respectively) but similar efficacy compared to lamotrigine (21%) for absence epilepsy syndromes. Although levetiracetam is often chosen due to a perceived favorable side effect profile, in our study rates of discontinuation due to side effects were similar to other medications. Children for whom levetiracetam is effective experience seizure freedom with a relatively low dose of this medication. Lack of seizure control requiring continued dose escalation should prompt early consideration of a therapeutic medication transition from levetiracetam to a first-line absence epilepsy medication. Funding: We acknowledge funding from the University of Michigan Charles Woodson Fund for Clinical Research.