Efficacy, tolerability, and safety of zonisamide in children with epileptic spasms: A systematic review and meta-analysis.

Abstract Background : Valproate, levetiracetam, benzodiazepines, and topiramate are antiseizure medications (ASMs) considered to have definite efficacy in reducing the frequency of epileptic spasm frequency, apart from ketogenic dietary therapies. Although zonisamide has also been shown to have efficacy as second-line ASM for epileptic spasms, various studies have conflicting results in literature. This systematic review aims to summarize clinical studies regarding the efficacy of zonisamide for epileptic spasms. Methods : We conducted a systematic literature search collating all available literature. The primary objective was to determine efficacy in terms of proportion with complete spasm resolution, we also intended to determine proportion with at least 50% spasm reduction, hypsarrhythmia resolution, and nature/frequency of adverse effects. All prospective/retrospective, controlled/uncontrolled studies describing the use of zonisamide with epileptic spasms were included in the qualitative review excluding case reports, but for metanalysis pertaining to key outcomes, we included studies with at least 10 participants. Results : A total of nineteen publications were found eligible for inclusion in the qualitative review, out of 101 search items. A total of 401 children with epileptic spasms were tried up to a maximum of 9.9-35 mg/kg/day dose with only mild adverse effects in a few patients. Total 20.8% (95% CI-11.4%-29.2%) and 23.4% (95% CI-17.8%-29.1%) patients had complete cessation of spasms and at least a 50% reduction in total spasm frequency as compared to baseline after starting zonisamide. Similarly, 20.3% (95% CI-10.1%-30.5%) had resolution of hypsarrhythmia in EEG after starting zonisamide. Conclusion : Zonisamide can reduce spasms in 21% of children with epileptic spasms, without major adverse effects. But there are only limited studies on epileptic spasms of sufficient quality to give high confidence in meta-analysis. Large controlled trials are needed in this regard to provide high-quality evidence favoring/disfavoring its use in patients with epileptic spasms.