Pretreatment behavior and subsequent medication effects in childhood absence epilepsy
Ruth C Shinnar1, Shlomo Shinnar2, Avital Cnaan2
1From Montefiore Medical Center (R.C.S., S.S., D.M., E.F.W.), Albert Einstein College of Medicine, Bronx, NY; George Washington University (A.C.), Washington, DC; Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine (P.C., C.L., T.A.G.), OH; The Children's Hospital of Philadelphia (D.D.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia; National Institute of Neurological Disorders and Stroke (D.G.H.); and Henry M. Jackson Foundation for the Advancement of Military Medicine (F.H.), Bethesda, MD. codell@sprynet.com.
Insights
Behavioral problems are common in children with childhood absence epilepsy (CAE). Valproic acid treatment is linked to worse behavioral outcomes compared to ethosuximide or lamotrigine.
Area of Science:
- Pediatric Neurology
- Child Psychiatry
- Epilepsy Research
Background:
- Childhood absence epilepsy (CAE) is a common epilepsy syndrome in children.
- Behavioral problems are frequently observed in children with CAE, impacting their quality of life.
- Understanding the interplay between CAE and behavioral issues is crucial for effective management.
Purpose of the Study:
- To investigate pretreatment behavioral problems in children diagnosed with CAE.
- To compare the differential effects of initial antiepileptic drug (AED) therapies on behavioral outcomes in CAE.
- To identify specific AEDs associated with improved or worsened behavioral profiles.
Main Methods:
- A randomized, double-blind trial involving children with CAE.
- Utilized the Child Behavior Checklist (CBCL) to assess behavioral problems at baseline, 16-20 weeks, and 12 months.
- Compared outcomes for children treated with ethosuximide, lamotrigine, and valproate, with total problems score as the primary measure.
Main Results:
- At baseline, 8% of children with CAE exhibited elevated total behavioral problems.
- After 16-20 weeks, valproic acid was associated with significantly higher scores for total, externalizing, attention, and attention-deficit/hyperactivity problems compared to ethosuximide.
- At 12 months, valproic acid continued to show higher attention problem scores than ethosuximide.
Conclusions:
- Pretreatment and ongoing behavioral problems are significant in children with CAE.
- Valproic acid is associated with poorer behavioral outcomes compared to ethosuximide and lamotrigine.
- Ethosuximide is reinforced as the preferred initial therapy for CAE due to better behavioral tolerability.
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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