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Efficacy and safety of perampanel in epilepsy: A systematic review and meta-analysis of randomised controlled trials

Published:September 28, 2022DOI:https://doi.org/10.1016/j.seizure.2022.09.020

      Highlights

      • This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE.
      • When compared with placebo, both 8 mg and 12 mg doses of perampanel showed similar efficacy in seizure control.
      • A higher risk of treatment discontinuation was found among 12 mg users than among 8 mg users.
      • The most reported TEAEs were non-threatening, with the potential possibility of rare but serious adverse psychological outcomes.
      • Further comparative effectiveness trials – as well as longitudinal follow-up observational studies – are needed to decide on the optimal doses for epilepsy management with perampanel.

      Abstract

      Background

      Perampanel a third-generation antiseizure medication, belongs to a new promising class of drugs called AMPA receptor antagonists, approved to treat focal-onset seizures with or without focal to bilateral tonic clonic seizures and primary generalized tonic-clonic seizures.

      Methods

      This review included RCTs on patients with epilepsy exposed to perampanel compared with placebo, or one or more pre-existing antiseizure medications. Four databases and two clinical trial registries were searched from inception to July 2021. Included outcomes were 50% responder rate, seizure-free rate, discontinuation due to treatment-emergent adverse events (TEAE)s, having any TEAEs, and most reported TEAEs. Cochrane risk of bias tool was used to assess the internal validity of the included RCTs.

      Results

      From 2211 retrieved citations, eight RCTs were included in the meta-analysis. Fifty-percent responder and seizure freedom rates were significantly higher in patients receiving perampanel when compared to placebo (RR 1.57, 95 % CI 1.35 to 1.82, I2 15% and RR 2.79, 95% CI 1.58 to 4.93, I2 7%, respectively). The 50% responder rates for 8mg and 12 mg, when compared to placebo, were similar. The most-reported TEAEs were dizziness and somnolence with <1% reporting serious psychological outcomes.

      Conclusion

      This systematic review reports significant reduction in seizures and a potential dose-based increase in discontinuations due to TEAE. The most-reported TEAEs were non-threatening, with the possibility of rare but serious adverse psychological outcomes. Further independent RCTs studying the most efficient dose for efficacy and safety are needed.

      Keywords

      Abbreviations:

      ASMs (Antiseizure medications), IPA (International pharmaceutical abstracts), CINAHL (Cumulative index of nursing and allied health literature, Cochrane risk-of-bias tool for randomised trials (RoB 2)), PRISMA (Preferred reporting items for systematic reviews and meta-analyses), RCT (Randomised controlled trials), TEAEs (Treatment emergent adverse events), WHO (World Health Organization), ICTRP (International Clinical Trials Registry Platform and RR: Risk ratios)
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