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Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta-analysis
Anna Rosati1, Lucrezia Ilvento1, Ersilia Lucenteforte2
1Neuroscience Center of Excellence, Meyer Children's Hospital, University of Florence, Florence, Italy.
Insights
Carbamazepine and lamotrigine are effective for newly diagnosed focal epilepsy. Levetiracetam and perampanel work for refractory focal epilepsy, while ethosuximide and valproic acid are better for absence seizures.
Area of Science:
- Pediatric Neurology
- Pharmacology
- Clinical Trials
Background:
- Epilepsy affects children and adolescents worldwide.
- Comparative efficacy data for antiepileptic drugs (AEDs) in pediatric populations is limited.
- Optimizing treatment requires understanding drug effectiveness in different epilepsy types.
Purpose of the Study:
- To conduct a network meta-analysis comparing the efficacy of various AEDs in children (0-18 years).
- To identify superior AEDs for newly diagnosed and refractory focal epilepsy, absence seizures, and infantile spasms.
Main Methods:
- Searched Embase and MEDLINE databases up to February 2017.
- Included 46 randomized clinical trials (RCTs) involving 5652 participants and 22 AEDs.
- Assessed study quality using the Cochrane risk-of-bias tool and followed PRISMA guidelines.
Main Results:
- Carbamazepine and lamotrigine showed superiority for newly diagnosed focal epilepsy.
- Levetiracetam and perampanel were more effective than placebo for refractory focal epilepsy.
- Ethosuximide and valproic acid outperformed lamotrigine for absence seizures; ACTH was superior for infantile spasms.
Conclusions:
- This network meta-analysis provides comparative efficacy data for AEDs in pediatric epilepsy.
- Findings highlight specific AEDs for different epilepsy syndromes.
- Future research should focus on improving study quality, outcome relevance, and follow-up duration.
Objective:
To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years).
Methods:
Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction.
Results:
We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies.
Significance:
This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.
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