Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy.
BACKGROUND
Childhood absence epilepsy, the most common pediatric epilepsy syndrome, is usually treated with ethosuximide, valproic acid, or lamotrigine. The most efficacious and tolerable initial empirical treatment has not been defined.


METHODS
In a double-blind, randomized, controlled clinical trial, we compared the efficacy, tolerability, and neuropsychological effects of ethosuximide, valproic acid, and lamotrigine in children with newly diagnosed childhood absence epilepsy. Drug doses were incrementally increased until the child was free of seizures, the maximal allowable or highest tolerable dose was reached, or a criterion indicating treatment failure was met. The primary outcome was freedom from treatment failure after 16 weeks of therapy; the secondary outcome was attentional dysfunction. Differential drug effects were determined by means of pairwise comparisons.


RESULTS
The 453 children who were randomly assigned to treatment with ethosuximide (156), lamotrigine (149), or valproic acid (148) were similar with respect to their demographic characteristics. After 16 weeks of therapy, the freedom-from-failure rates for ethosuximide and valproic acid were similar (53% and 58%, respectively; odds ratio with valproic acid vs. ethosuximide, 1.26; 95% confidence interval [CI], 0.80 to 1.98; P=0.35) and were higher than the rate for lamotrigine (29%; odds ratio with ethosuximide vs. lamotrigine, 2.66; 95% CI, 1.65 to 4.28; odds ratio with valproic acid vs. lamotrigine, 3.34; 95% CI, 2.06 to 5.42; P<0.001 for both comparisons). There were no significant differences among the three drugs with regard to discontinuation because of adverse events. Attentional dysfunction was more common with valproic acid than with ethosuximide (in 49% of the children vs. 33%; odds ratio, 1.95; 95% CI, 1.12 to 3.41; P=0.03).


CONCLUSIONS
Ethosuximide and valproic acid are more effective than lamotrigine in the treatment of childhood absence epilepsy. Ethosuximide is associated with fewer adverse attentional effects. (ClinicalTrials.gov number, NCT00088452.)
Glauser
Tracy A
TA
Comprehensive Epilepsy Center, Division of Neurology, Cincinnati Children's Hospital, 3333 Burnet Ave., MLC 2015, Cincinnati, OH 45229, USA. tracy.glauser@cchmc.org
Cnaan
Avital
A
Shinnar
Shlomo
S
Hirtz
Deborah G
DG
Dlugos
Dennis
D
Masur
David
D
Clark
Peggy O
PO
Capparelli
Edmund V
EV
Adamson
Peter C
PC
D000293:Adolescent; D000704:Analysis of Variance; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D019958:Attention Deficit and Disruptive Behavior Disorders / Q000139:chemically induced; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D004832:Epilepsy, Absence / Q000188:drug therapy*; D005013:Ethosuximide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D000077213:Lamotrigine; D008297:Male; D012640:Seizures / Q000139:chemically induced; D016896:Treatment Outcome; D014227:Triazines / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D014635:Valproic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
D000927:Anticonvulsants; D014227:Triazines; D005013:Ethosuximide; D014635:Valproic Acid; D000077213:Lamotrigine