Reduction of epileptiform activity in response to low-dose clonazepam in children with epilepsy: a randomized
M Dahlin1, E Knutsson, P Amark
1Department of Pediatrics, Karolinska Hospital, Stockholm, Sweden. marda@child.ks.se
Insights
Low-dose clonazepam significantly reduced epileptiform activity and seizures in children with epilepsy, even at lower plasma levels than typically recommended. This study highlights a potential new therapeutic approach for pediatric epilepsy management.
Area of Science:
- Pediatric Neurology
- Clinical Pharmacology
- Epileptology
Background:
- Epilepsy affects numerous children worldwide, necessitating effective treatment strategies.
- Current treatments for pediatric epilepsy often involve significant side effects.
- Exploring lower, effective doses of established antiepileptic drugs is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the efficacy of a low dose of clonazepam (CZP) in reducing epileptiform activity in children with epilepsy.
- To assess the impact of low-dose CZP on seizure frequency in pediatric patients.
- To correlate plasma concentrations of CZP with its antiseizure effects.
Main Methods:
- A pilot study followed by a double-blind, placebo-controlled, randomized crossover design.
- 15 children with epilepsy underwent 24-h long-term EEG monitoring.
- Low-dose clonazepam (0.02 mg/kg BW) was administered via intramuscular injection, with regular blood sampling for plasma concentration analysis.
Main Results:
- A highly significant reduction (p = 0.0015) in epileptiform activity was observed with low-dose CZP compared to placebo (-69% vs. -2%).
- Median plasma concentrations of CZP ranged from 18 to <14 nM during the analysis periods.
- Children experiencing daily seizures showed a parallel decrease in both seizures and epileptiform discharges.
Conclusions:
- A single low dose of clonazepam significantly reduces epileptiform discharges on EEG in children with epilepsy.
- The observed therapeutic effects were achieved at considerably lower plasma levels than usually recommended.
- Concomitant reduction in seizures suggests a potential benefit of low-dose CZP in managing pediatric epilepsy.
Purpose:
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.
