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

Collaborators, Affiliations

Collaborators

Childhood Absence Epilepsy Study Group:
Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Ricardo Luzondo, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc

Affiliations

¹ From 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.
² From 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.

PMID: 28916534
PMCID: PMC5644466
DOI: 10.1212/WNL.0000000000004514

Randomized Controlled Trial

Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

Ruth C Shinnar et al. Neurology. 2017.

. 2017 Oct 17;89(16):1698-1706.

doi: 10.1212/WNL.0000000000004514. Epub 2017 Sep 15.

Collaborators

Childhood Absence Epilepsy Study Group:
Harry Abram, Ellen Albers, Samar J Bahna, Karen Ballaban-Gil, Jose Barrera, Tekolla Belaineh, Mary Bertrand, Hal Blumenfeld, Sarah Borror, Charlie Borzy, Susan Brantz, Candace Cardoza, Kevin Chapman, Harry T Chugani, Robert R Clancy, Peggy O Clark, Yong Collins, Terrie Conklin, Joan A Conry, Patricia K Crumrine, Jason Czachor, M Susan Dean, Sandra Dewar, Michael Duchowny, Deborah Dye, Tammy Eaton, Mary Jo Elgie, Michelle Ellis, Roy Elterman, Daniella Escobedo, Andrew Francis, L Matthew Frank, Tracy A Glauser, Hilary Gray, La June Grayson, May L Griebel, Laurie Guidry, Samantha Hagopian, Jennifer Haky, Amelia Halac, Angel Hernandez, Lee Howard, Krisa Hoyle Elgin, Pong Kankirawatana, Kent R Kelley, Juli Kidd, Divya Khurana, Paul M Levisohn, Donna Lowery, Ricardo Luzondo, Mary Lou Maher, Angela Martinez, Karen McEwen, Sarah J McVey, Mary Miceli, Daniel K Miles, Jennifer Monahan, Elena Morales, Dianne Morus, Cyndi Mott, JoAnn Narus, Mark Nespeca, Edward Novotny Jr, Suzanne Oken, Juliann Paolicchi, Bryan Philbrook, Tami Quintero, Amber Reese-Porter, Jong M Rho, Tracee Ridley-Pryor, Angela Riggs, Colin Roberts, Kathy Romine, Veronique Ruppe, Russell P Saneto, Raman Sankar, Mark S Scher, Rebecca Schultz, Michael Schwabe, Dina Schwam, Sagar Shah, Gregory Sharp, Rolla Shbarou, Ruth C Shinnar, Shlomo Shinnar, Marcio Sotero de Menezes, Donovan Stock, Christina Lopez Talley, Susanna Taylor, Mamello Tekateka, Doris A Trauner, Edwin Trevathan, William R Turk, Colin B Van Orman, GeorgAnn Vanderjagt, Mary Warde, Jorge Vidaurre, Arie Weinstock, Nanastasia Welnick, Rhonda Werner, James Wheless, Angus A Wilfong, Korwyn Willliams, Shelley Williams, Teresa Williams, Jennifer Williamson, Khaled Zamel, Mary Zupanc

Affiliations

¹ From 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.
² From 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.

PMID: 28916534
PMCID: PMC5644466
DOI: 10.1212/WNL.0000000000004514

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. 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

Behavior Problems in Childhood Absence Epilepsy: A Chicken or Egg Problem.
Salpekar J. Salpekar J. Epilepsy Curr. 2018 Mar-Apr;18(2):97-98. doi: 10.5698/1535-7597.18.2.97. Epilepsy Curr. 2018. PMID: 29670485 Free PMC article. No abstract available.

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Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

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Pretreatment behavior and subsequent medication effects in childhood absence epilepsy

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