Objectives: This study was aimed to assess the short-term and long-term efficacy and safety of ASMs for the management of Lennox Gastaut Syndrome (LGS).

Methods: PubMed and Embase was used to retrieved the citations from inception till June 2021. Randomized controlled trials and open-label extension studies on LGS comparing different ASMs with placebo or with other ASMs for short-term and long-term duration were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary outcomes. A network meta-analysis was applied to the short-term outcomes, and these were reported as odds ratio (OR) with 95% confidence intervals (CIs). The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve (SUCRA). Additionally, long-term outcomes were reported as proportion with 95% CIs using the random-effects model.

Results: 15 studies including 1263 participants with LGS (aged 2-54 years) receiving any of six different ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. CLB 1.0 mg/kg/day [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with a ≥50% reduction in drop seizure frequency as compared with placebo and achieved the highest-ranking probability (0.89) based on SUCRA values, while CBD 20 mg/kg/day [OR: 3.8; 95% CI: 1.6-9.0] had significantly higher odds for the occurrence of any TEAEs and had the highest-ranking probability (0.85). For long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs.

Conclusion: CLB 1.0 mg/kg/day had the best efficacy and safety profile compared with other included ASMs. Future head-to-head trials comparing these ASMs are needed to understand their comparative efficacy and safety better.