Adjunctive levetiracetam in infants and young children with refractory partial‐onset seizures

• Published in: Epilepsia (Copenhagen) Vol. 50; no. 5; pp. 1141 - 1149
• Main Authors: Piña‐Garza, Jesus Eric, Nordli Jr, Douglas R., Rating, Dietz, Yang, Haichen, Schiemann‐Delgado, Jimmy, Duncan, Benjamin
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-05-2009; Wiley-Blackwell
• Subjects: Anticonvulsants - therapeutic use; Anticonvulsants. Antiepileptics. Antiparkinson agents; Antiepileptic drug; Biological and medical sciences; Child, Preschool; Children; Confidence Intervals; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Electroencephalography - methods; Epilepsies, Partial - drug therapy; Epilepsy; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; Infant; Infant, Newborn; International Cooperation; Levetiracetam; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; Odds Ratio; Partial seizures; Pharmacology. Drug treatments; Piracetam - analogs & derivatives; Piracetam - therapeutic use; Retrospective Studies; Time Factors; Treatment Outcome; Videotape Recording - methods; Human; Antiepileptic drug; Nervous system diseases; Psychotropic; Epilepsy; Infant; Anticonvulsant; Partial seizures; Cerebral disorder; Refractory; Convulsion; Nootropic agent; Central nervous system disease; Children; Neurological disorder; Child; Levetiracetam
• ISSN: 0013-9580; 1528-1167
• DOI: 10.1111/j.1528-1167.2008.01981.x

Summary
Purpose:  To evaluate the efficacy and tolerability of adjunctive levetiracetam in very young children (aged 1 month to <4 years) with partial‐onset seizures inadequately controlled with one or two antiepileptic drugs.
Methods:  This multicenter, double‐blind, randomized, placebo‐controlled study consisted of a 48‐h inpatient baseline video‐EEG (electroencephalography) and a 5‐day inpatient treatment period (1‐day up‐titration; 48‐h evaluation video‐EEG in the last 2 days). Children who experienced at least two partial‐onset seizures during the 48‐h baseline video‐EEG were randomized to either levetiracetam [40 mg/kg/day (age 1 to <6 months); 50 mg/kg/day (age ≥6 months to <4 years] or placebo.
Results:  Of 175 patients screened, 116 patients were randomized [60 levetiracetam; 56 placebo; intent‐to‐treat (ITT) population], and 111 completed the study. The responder rate in average daily partial‐onset seizures frequency (48‐h video‐EEG monitoring; primary efficacy variable) was 43.1% for levetiracetam [modified ITT (mITT) = 58] versus 19.6% for placebo (mITT = 51; p=0.013), with odds ratio for response 3.11 [95% confidence interval (CI), 1.22–8.26]. The median percent reduction from baseline in average daily partial‐onset seizure frequency was 43.6% for levetiracetam and 7.1% for placebo with a median difference between treatment groups of 39.2% (95% CI, 17.5–62.2; p < 0.001). In general, levetiracetam was well tolerated. Treatment‐emergent adverse events were reported by 55.0% levetiracetam‐ and 44.6% placebo‐treated patients (ITT population). The most frequently reported adverse events were somnolence (13.3% levetiracetam, 1.8% placebo) and irritability (11.7% levetiracetam, 0% placebo).
Discussion:  Adjunctive levetiracetam is an efficacious and well‐tolerated treatment for partial‐onset seizures in infants and young children.