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Randomized Controlled Trial
. 2017 Oct 17;89(16):1698-1706.
doi: 10.1212/WNL.0000000000004514. Epub 2017 Sep 15.

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

Ruth C Shinnar  1 , Shlomo Shinnar  2 , Avital Cnaan  2 , Peggy Clark  2 , Dennis Dlugos  2 , Deborah G Hirtz  2 , Fengming Hu  2 , Chunyan Liu  2 , David Masur  2 , Erica F Weiss  2 , Tracy A Glauser  2 ; Childhood Absence Epilepsy Study Group
Collaborators, Affiliations
Randomized Controlled Trial

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

Ruth C Shinnar et al. Neurology. .

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.

Clinicaltrialsgov 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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Figures

Figure 1
Figure 1. Child Behavior Checklist (CBCL) testing in participants during the initial 12 months of double-blind treatment
CAE = childhood absence epilepsy; ETX = ethosuximide; LTG = lamotrigine; VPA = valproic acid.
See this image and copyright information in PMC

Comment in

References

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