Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy

Abstract

IMPORTANCE More than half of infants with new-onset epilepsy have electroencephalographic and clinical features that do not conform to known electroclinical syndromes (ie, nonsyndromic epilepsy). Levetiracetam and phenobarbital are the most commonly prescribed medications for epilepsy in infants, but their comparative effectiveness is unknown. OBJECTIVE To compare the effectiveness of levetiracetam vs phenobarbital for nonsyndromic infantile epilepsy. DESIGN, SETTING, AND PARTICIPANTS The Early Life Epilepsy Study-a prospective, multicenter, observational cohort study conducted from March 1, 2012, to April 30, 2015, in 17 US medical centers-enrolled infants with nonsyndromic epilepsy and a first afebrile seizure between 1 month and 1 year of age. EXPOSURES Use of levetiracetam or phenobarbital as initial monotherapy within 1 year of the first seizure. MAIN OUTCOMES AND MEASURES The binary outcome was freedom from monotherapy failure at 6 months, defined as no second prescribed antiepileptic medication and freedom from seizures beginning within 3 months of initiation of treatment. Outcomes were adjusted for demographics, epilepsy characteristics, and neurologic history, as well as for observable selection bias using propensity score weighting and for within-center correlation using generalized estimating equations. RESULTS Of the 155 infants in the study (81 girls and 74 boys; median age, 4.7 months [interquartile range, 3.0-7.1 months]), those treated with levetiracetam (n = 117) were older at the time of the first seizure than those treated with phenobarbital (n = 38) (median age, 5.2 months [interquartile range, 3.5-8.2 months] vs 3.0 months [interquartile range, 2.0-4.4 months]; P < .001). There were no other significant bivariate differences. Infants treated with levetiracetam were free from monotherapy failure more often than those treated with phenobarbital (47 [40.2%] vs 6 [15.8%]; P = .01). The superiority of levetiracetam over phenobarbital persisted after adjusting for covariates, observable selection bias, and within-center correlation (odds ratio, 4.2; 95% CI, 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). CONCLUSIONS AND RELEVANCE Levetiracetam may have superior effectiveness compared with phenobarbital for initial monotherapy of nonsyndromic epilepsy in infants. If 100 infants who received phenobarbital were instead treated with levetiracetam, 44 would be free from monotherapy failure instead of 16 by the estimates in this study. Randomized clinical trials are necessary to confirm these findings.

Automated detection of sudden unexpected death in epilepsy risk factors in electronic medical records using natural language processing

“…Hospitals may not currently have the necessary support for implementation and maintenance of regular expressions. 39,40 Steps to increase data utility for epilepsy research include (1) continued collaboration between institutions to share data for epilepsy research, 41,42 (2) building structured data elements into physician note templates to improve documentation at the point of care for later use in epilepsy research, (3) continued development of epilepsy-specific NLP tools to extract valuable information from unstructured clinical narratives in EMRs, [28][29][30][31]38 (4) increased adoption of standard epilepsy classification systems 43,44 to improve consistency of language used in EMRs, and (5) continued development of epilepsy-specific ontologies 45 and vocabularies 37 for epilepsy researchers using EMR data. We performed data analysis on a research server, after data were extracted from the EMR.…”

Neurodevelopmental outcomes at 9–14 months gestational age after treatment of neonatal seizures due to brain injury

“…A higher proportion of infants in the phenobarbital group had developmental structural brain abnormalities. 30 Our study focuses on neonatal seizures in a population with brain injury and suggests no difference in treatment failure or neurodevelopmental outcomes for these infants.…”

Levetiracetam is Less Effective than Phenobarbital in Treating Seizures Associated with KCNQ2 Variant of Benign Familial Neonatal Convulsions

“…7 A multicenter observational cohort study comparing the efficacy of levetiracetam and phenobarbital in infants with nonsyndromic epilepsy presenting between 1 month and 1 year of age found that levetiracetam was superior as initial monotherapy. 8 Shellhaas et al 9 enrolled newborns with seizures from seven United States Children's Hospitals. BFNC was found clinically in 11 of 611 neonates.…”