Neurocognitive effects of adjunctive levetiracetam in children with partial-onset seizures: a randomized, double-blind, placebo-controlled, noninferiority trial.
OBJECTIVE
Evaluate potential neurocognitive effects of adjunctive levetiracetam in children with inadequately controlled partial-onset seizures (POS).


METHODS
Randomized, double-blind, placebo-controlled, noninferiority safety study. Children (4-16 years; IQ > or =65) with > or =1 POS during 4 weeks before screening despite taking 1-2 antiepileptic drugs (AEDs) were randomized (2:1) to levetiracetam (20-60 mg/kg/day) or placebo for 12 weeks.


RESULTS
Ninety-nine patients were randomized with 98 (levetiracetam 64, placebo 34) in intent-to-treat (ITT) and 73 (levetiracetam 46, placebo 27) in per protocol (PP) populations. Primary cognitive assessment was the Leiter International Performance Scale-Revised Attention and Memory Battery with the memory screen composite score change from baseline as the primary endpoint. PP Least Square Mean [LSM (standard error)] were 5.36 (1.78) for levetiracetam; 5.17 (2.33) for placebo; difference [two-sided 90% confidence interval (CI)] 0.19 (-4.69, 5.08). Levetiracetam was noninferior to placebo because the 90% CI lower bound was greater than the defined noninferiority margin (-9.0). There were no statistically significant differences between groups in Wide Range Assessment of Memory and Learning-2 indexes and Leiter-R Examiner's Rating Scale scores. Median reductions from baseline in weekly POS frequency were 91.5% versus 26.5% for levetiracetam versus placebo; > or =50% responder rates: 62.5% versus 41.2%; seizure freedom rates: 46.9% versus 8.8% (ITT). Adverse events were reported by 89.1% levetiracetam-treated and 85.3% placebo-treated patients; those reported by > or =10% levetiracetam patients and more often with levetiracetam were headache, nasopharyngitis, fatigue, vomiting, somnolence, and aggression.


CONCLUSIONS
Neurocognitive effects were no different in pediatric patients with POS treated with adjunctive levetiracetam or placebo. Levetiracetam was effective and well tolerated.
Levisohn
Paul M
PM
Department of Pediatric Neurology, Children's Hospital, Denver, Colorado 80045, USA.
Mintz
Mark
M
Hunter
Scott J
SJ
Yang
Haichen
H
Jones
John
J
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology; D015897:Comorbidity; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010889:Piracetam / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010919:Placebos; D016896:Treatment Outcome
D000927:Anticonvulsants; D010919:Placebos; D000077287:Levetiracetam; D010889:Piracetam