Reduction of epileptiform activity in response to low-dose clonazepam in children with epilepsy: a randomized double-blind study.
OBJECTIVE
To evaluate the effect of low-dose clonazepam (CZP) on the amount of epileptiform activity in children with focal and generalized epilepsy.


METHODS
In a single-blind pilot study, followed by a double-blind, placebo-controlled, randomized, crossover study, 15 children with epilepsy were evaluated by using 24-h long-term EEG recordings during baseline days and days after injections of placebo and CZP. The drug was given as a single i.m. injection of 0.02 mg/kg BW. Blood samples were obtained regularly for analysis of plasma concentrations of CZP. The number of epileptiform discharges was determined during corresponding periods with the individual child in the same state of alertness, the same real time of day, and with concomitant antiepileptic drugs (AEDs) unchanged.


RESULTS
In the double-blind study, low-dose CZP produced a highly significant (p = 0.0015) decrease in the amount of epileptiform activity (mean, -69% vs. placebo, -2%) obtained during periods when median plasma concentrations ranged from 18 to <14 nM. The maximal plasma level (median, 24 nM) was reached before the start of the analysis periods. The pilot study showed reductions of epileptiform discharges within the same range as the double-blind study. In the children with daily seizures, a parallel decrease in seizures and the number of epileptiform discharges was seen after the administration of CZP.


CONCLUSIONS
Our data demonstrate a significant reduction of epileptiform discharges on long-term EEGs after a single low dose of CZP with concomitant low plasma levels, which were considerably lower than the doses and plasma levels usually recommended. A concomitant reduction of seizures also was seen.
Dahlin
M
M
Department of Pediatrics, Karolinska Hospital, Stockholm, Sweden. marda@child.ks.se
Knutsson
E
E
Amark
P
P
Nergårdh
A
A
D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002998:Clonazepam / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000706:statistics & numerical data; D004828:Epilepsies, Partial / Q000188:drug therapy; D004827:Epilepsy / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004829:Epilepsy, Generalized / Q000188:drug therapy; D005260:Female; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D008297:Male; D010865:Pilot Projects; D010919:Placebos; D016896:Treatment Outcome; D014743:Videotape Recording
D000927:Anticonvulsants; D010919:Placebos; D002998:Clonazepam