Summary

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• This summary is based on the review of 13 systematic review(s)/meta-analysis(es). ^[1-13]
• Cenobamate demonstrated a relative risk (RR) of 2.17 for achieving a ≥50% reduction in seizure frequency compared to placebo, with responder rates of 52% for cenobamate versus 24% for placebo (moderate-certainty evidence). Additionally, the RR for seizure reduction was consistently reported across multiple studies, with values of 2.06 and 2.18 noted.
• The RR for achieving seizure freedom with cenobamate was 4.45 compared to placebo, with freedom rates of 16% versus 5%. Pooled estimates reported an RR of 3.71, indicating cenobamate's superior efficacy in promoting seizure freedom.
• Cenobamate was found to be more effective than other anti-seizure medications (ASMs), showing higher responder rates compared to brivaracetam, eslicarbazepine, lacosamide, and perampanel, and achieving a 100% responder rate superior to eslicarbazepine and zonisamide.
• The populations studied primarily included adults with focal epilepsy, particularly those with drug-resistant focal-onset seizures. However, further investigation into cenobamate's efficacy and tolerability in children and its use as monotherapy is warranted.
• Cenobamate was associated with an RR of 1.14 for adverse events compared to placebo, with rates of 77% for cenobamate versus 67% for placebo (moderate-certainty evidence). Common adverse events included somnolence, dizziness, fatigue, balance disorder, and diplopia.
• Higher rates of treatment-emergent adverse events (TEAEs) leading to discontinuation were observed with cenobamate compared to some other ASMs, although these differences were not statistically significant. Cenobamate's higher incidence of serious adverse events was noted at increased dosages.
• Despite a higher rate of adverse events, the incidence of serious adverse events and dropouts due to adverse events with cenobamate was not significantly higher compared to placebo, although higher doses (400 mg) were associated with increased dropouts.
• Cenobamate is primarily studied in adults with focal epilepsy, particularly those with drug-resistant focal-onset seizures, and shows significant efficacy in this population. However, further research is needed to evaluate its efficacy and tolerability in children and as monotherapy, with indications that the most effective dose may be 400 mg, though this is associated with higher dropout rates.