Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

Ruth C. Shinnar, Shlomo Shinnar, Avital Cnaan, Peggy Clark, Dennis Dlugos, Deborah G. Hirtz, Fengming Hu, Chunyan Liu, David Masur, Erica F. Weiss, Tracy A. Glauser

Research output: Contribution to journalArticle

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Abstract

Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. Results: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%-11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6-54.7]), externalizing problems (51.4 [98.3% CI 48.5-54.3]), attention problems (57.8 [98.3% CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4-49.6]; 45.8 [98.3% CI 42.9-48.7]; 54.6 [98.3% CI 52.4-56.9]; 53.0 [98.3% CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1-56.9]). Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. Clinicaltrials.gov identifier: NCT00088452. Classification of evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.

Original languageEnglish (US)
Pages (from-to)1698-1706
Number of pages9
JournalNeurology
Volume89
Issue number16
DOIs
StatePublished - Oct 17 2017

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Absence Epilepsy
Ethosuximide
Confidence Intervals
Valproic Acid
Child Behavior
Checklist
Seizures
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Shinnar, R. C., Shinnar, S., Cnaan, A., Clark, P., Dlugos, D., Hirtz, D. G., ... Glauser, T. A. (2017). Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. Neurology, 89(16), 1698-1706. https://doi.org/10.1212/WNL.0000000000004514

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. / Shinnar, Ruth C.; Shinnar, Shlomo; Cnaan, Avital; Clark, Peggy; Dlugos, Dennis; Hirtz, Deborah G.; Hu, Fengming; Liu, Chunyan; Masur, David; Weiss, Erica F.; Glauser, Tracy A.

In: Neurology, Vol. 89, No. 16, 17.10.2017, p. 1698-1706.

Research output: Contribution to journalArticle

Shinnar, RC, Shinnar, S, Cnaan, A, Clark, P, Dlugos, D, Hirtz, DG, Hu, F, Liu, C, Masur, D, Weiss, EF & Glauser, TA 2017, 'Pretreatment behavior and subsequent medication effects in childhood absence epilepsy', Neurology, vol. 89, no. 16, pp. 1698-1706. https://doi.org/10.1212/WNL.0000000000004514
Shinnar, Ruth C. ; Shinnar, Shlomo ; Cnaan, Avital ; Clark, Peggy ; Dlugos, Dennis ; Hirtz, Deborah G. ; Hu, Fengming ; Liu, Chunyan ; Masur, David ; Weiss, Erica F. ; Glauser, Tracy A. / Pretreatment behavior and subsequent medication effects in childhood absence epilepsy. In: Neurology. 2017 ; Vol. 89, No. 16. pp. 1698-1706.
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abstract = "Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. Results: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8{\%} (95{\%} confidence interval [CI] 6{\%}-11{\%}) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3{\%} CI 48.6-54.7]), externalizing problems (51.4 [98.3{\%} CI 48.5-54.3]), attention problems (57.8 [98.3{\%} CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3{\%} CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3{\%} CI 43.4-49.6]; 45.8 [98.3{\%} CI 42.9-48.7]; 54.6 [98.3{\%} CI 52.4-56.9]; 53.0 [98.3{\%} CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3{\%} CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95{\%} CI 52.1-56.9]). Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. Clinicaltrials.gov identifier: NCT00088452. Classification of evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.",
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AU - Shinnar, Ruth C.

AU - Shinnar, Shlomo

AU - Cnaan, Avital

AU - Clark, Peggy

AU - Dlugos, Dennis

AU - Hirtz, Deborah G.

AU - Hu, Fengming

AU - Liu, Chunyan

AU - Masur, David

AU - Weiss, Erica F.

AU - Glauser, Tracy A.

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N2 - Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. Results: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%-11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6-54.7]), externalizing problems (51.4 [98.3% CI 48.5-54.3]), attention problems (57.8 [98.3% CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4-49.6]; 45.8 [98.3% CI 42.9-48.7]; 54.6 [98.3% CI 52.4-56.9]; 53.0 [98.3% CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1-56.9]). Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. Clinicaltrials.gov identifier: NCT00088452. Classification of evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.

AB - Objective: To characterize pretreatment behavioral problems and differential effects of initial therapy in children with childhood absence epilepsy (CAE). Methods: The Child Behavior Checklist (CBCL) was administered at baseline, week 16-20, and month 12 visits of a randomized double-blind trial of ethosuximide, lamotrigine, and valproate. Total problems score was the primary outcome measure. Results: A total of 382 participants at baseline, 310 participants at the week 16-20 visit, and 168 participants at the month 12 visit had CBCL data. At baseline, 8% (95% confidence interval [CI] 6%-11%) of children with CAE had elevated total problems scores (mean 52.9 ± 10.91). At week 16-20, participants taking valproic acid had significantly higher total problems (51.7 [98.3% CI 48.6-54.7]), externalizing problems (51.4 [98.3% CI 48.5-54.3]), attention problems (57.8 [98.3% CI 55.6-60.0]), and attention-deficit/hyperactivity problems (55.8 [98.3% CI 54.1-57.6]) scores compared to participants taking ethosuximide (46.5 [98.3% CI 43.4-49.6]; 45.8 [98.3% CI 42.9-48.7]; 54.6 [98.3% CI 52.4-56.9]; 53.0 [98.3% CI 51.3-54.8]). Lack of seizure freedom and elevated week 16-20 Conner Continuous Performance Test confidence index were associated with worse total problems scores. At month 12, participants taking valproic acid had significantly higher attention problems scores (57.9 [98.3% CI 55.6-60.3]) compared to participants taking ethosuximide (54.5 [95% CI 52.1-56.9]). Conclusions: Pretreatment and ongoing behavioral problems exist in CAE. Valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine, further reinforcing ethosuximide as the preferred initial therapy for CAE. Clinicaltrials.gov identifier: NCT00088452. Classification of evidence: This study provides Class II evidence that for children with CAE, valproic acid is associated with worse behavioral outcomes than ethosuximide or lamotrigine.

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