Medications for Early Life Epilepsy: Evidence Versus Experience?

Research output: Contribution to journalComment/debate

Abstract

Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017.5211. 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 versus 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% confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). Conclusions and Relevance: Levetiracetam may have superior effectiveness compared to 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.

Original languageEnglish (US)
Pages (from-to)33-35
Number of pages3
JournalEpilepsy Currents
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

etiracetam
Phenobarbital
Epilepsy
Seizures
Selection Bias
Confidence Intervals
Numbers Needed To Treat
Propensity Score

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Medications for Early Life Epilepsy : Evidence Versus Experience? / Nickels, Katherine.

In: Epilepsy Currents, Vol. 19, No. 1, 01.01.2019, p. 33-35.

Research output: Contribution to journalComment/debate

@article{e4d4222ccfe14a08b2af50df35bacdfd,
title = "Medications for Early Life Epilepsy: Evidence Versus Experience?",
abstract = "Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017.5211. 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 versus 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{\%} confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95{\%} CI, 1.7-60]). Conclusions and Relevance: Levetiracetam may have superior effectiveness compared to 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.",
author = "Katherine Nickels",
year = "2019",
month = "1",
day = "1",
doi = "10.1177/1535759718822130",
language = "English (US)",
volume = "19",
pages = "33--35",
journal = "Epilepsy Currents",
issn = "1535-7597",
publisher = "American Epilepsy Society",
number = "1",

}

TY - JOUR

T1 - Medications for Early Life Epilepsy

T2 - Evidence Versus Experience?

AU - Nickels, Katherine

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017.5211. 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 versus 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% confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). Conclusions and Relevance: Levetiracetam may have superior effectiveness compared to 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.

AB - Comparative Effectiveness of Levetiracetam vs Phenobarbital for Infantile Epilepsy Grinspan ZM, Shellhaas RA, Coryell J, Sullivan JE, Wirrell EC, Mytinger JR, Gaillard WD, Kossoff EH, Valencia I, Knupp KG, Wusthoff C, Keator C, Ryan N, Loddenkemper T, Chu CJ, Novotny EJ Jr, Millichap J, Berg AT. JAMA Pediatr. 2018 Apr 1;172(4):352-360. doi: 10.1001/jamapediatrics.2017.5211. 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 versus 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% confidence interval [CI], 1.1-16; number needed to treat, 3.5 [95% CI, 1.7-60]). Conclusions and Relevance: Levetiracetam may have superior effectiveness compared to 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.

UR - http://www.scopus.com/inward/record.url?scp=85061185825&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061185825&partnerID=8YFLogxK

U2 - 10.1177/1535759718822130

DO - 10.1177/1535759718822130

M3 - Comment/debate

AN - SCOPUS:85061185825

VL - 19

SP - 33

EP - 35

JO - Epilepsy Currents

JF - Epilepsy Currents

SN - 1535-7597

IS - 1

ER -