The efficacy and safety of antiepileptics in the prophylaxis of pediatric migraine: the meta-analysis of randomized controlled trials

BACKGROUND: Migraine is the most common primary headache among children and adolescents. The aim of this meta-analysis was to evaluate the efficacy and safety of antiepileptic drugs in the prevention of pediatric migraine. METHODS: PubMed, Cochrane Library, EMBASE and Chinese National Knowledge Infrastructure (CNKI) databases were searched for eligible published RCTs from January 1970 to June 2020. Migraine frequency and ≥50% response rate were measured as the efficacy outcomes. We used “Risk of Bias” tool for quality assessment and RevMan5.3 software for statistical analysis. RESULTS: Four articles containing 7 RCTs with 794 participants compared the efficacy of AEDs with placebo. Four RCTs assessed topiramate vs. placebo and 3 RCTs evaluated divalproex sodium extended-release (DVPX ER) vs. placebo. The results demonstrated that children receiving antiepileptic drugs had a significant advantage in remitting the mean monthly migraine days compared to those who received placebo, with an MD of −0.48 (n=930, 95% CI: −0.84 to −0.12, Z=2.60, P=0.009). Topiramate significantly reduced monthly migraine days (MD =−0.70, n=489, 95% CI: −1.16 to −0.25, Z=3.01, P=0.003) but failed to improve the ≥50% response rate (MD =−1.50, n=489, 95% CI: 0.70 to 3.22, Z=1.05, P=0.30). DVPX ER did not significantly reduce monthly headache frequency (n=441, 95% CI: −0.70 to 0.47, Z=0.38, P=0.70) or improve the ≥50% response rate (n=441, 95% CI: 0.59 to 1.25, Z=0.82, P=0.41) compared with placebo. Topiramate and DVPX ER were related to higher rates of side effects and adverse reactions. DISCUSSION: Topiramate can reduce monthly headache days in children and adolescents with migraine. However, it failed to improve the ≥50% response rate. DVPX ER showed no difference from placebo in the prophylactic treatment pediatric migraine. Side effects seemed to be more frequent in topiramate and DVPX ER treated children but generally well-tolerated.