Gabapentin as Add-On Therapy for Refractory Partial Seizures in Children 1-36 Months of Age: A Novel, Short-Term, Placebo-Controlled Trial
Abstract number :
2.065
Submission category :
Year :
2000
Submission ID :
2448
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Douglas Y Shapiro, Douglas Nordli, Tracy A Glauser, Lloyd E Knapp, Martha Greiner, Thomas J Purcell, Mitchell G Brigell, Klaus Fichtner, Alan R Kugler, Michael Malicsi, Tzena M Smith, Elizabeth A Garofalo, Pfizer Global Research and Development, Ann Arbor
RATIONALE: We developed and employed a novel design to assess efficacy of antiepileptic drugs (AED) in young children with refractory partial seizures. METHODS: The study was designed to deal with the difficulty of diagnosis in this age, uncertain reliability of seizure diaries, high variability in seizure rate, and the small number of available patients. Partial seizures were diagnosed either (1) by matching clinical semiology with imaging/EEG evidence of localized lesions, or (2) by EEG capture of a focal seizure. Eligible patients, aged 1-36 months, whose seizures were not controlled by at least 1 AED, entered a 2-day baseline period in which seizures were captured on continuous video-EEG monitoring for 48 h, in hospital or at home. Patients (n=76)were then randomly assigned to receive a syrup formulation of gabapentin, 40 mg/kg/day given TID (n=38), or placebo (n=38), during a 3-day double-blind phase with continuous video-EEG monitoring for 72h. The number of partial seizures was counted by a central EEG-reader blinded to treatment assignment. Efficacy was measured by the Response Ratio (a measure of proportional change in the rate of partial seizures between baseline and double-blind phases) and the responder rate (% patients whose seizure rate declined by at least 50% from baseline). RESULTS: Treatment groups were similar in gender, race, age, and history of seizure type. The Response Ratio for gabapentin-treated patients was -0.048 (a reduction in seizure rate), while that of placebo-treated patients was 0.018 (a worsening). The difference between the 2 treatment groups was not statistically significant, but was similar in magnitude to the statistically significant difference found in a larger, positive study previously conducted in older children. Responder rates were identical between treatment groups. Most frequent adverse events were somnolence, nausea and vomiting. CONCLUSIONS: Gabapentin was safe and well tolerated; it reduced the rate of partial seizures but not to levels significantly different from placebo. The study proved the feasibility of a shortterm study of AEDs in very young children.