Systematic review and meta-analysis of the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

Abstract

INTRODUCTION:

Perampanel is a first-in-class antiepileptic drug approved for adjunctive treatment of partial-onset seizure in patients aged 12 years or older. Published randomised controlled trials (RCTs) had small sample sizes, and meta-analyses have included too few studies to draw conclusive results for the assessment of tolerability, efficacy and safety of perampanel. There is a need to conduct a meta-analysis with a larger dataset and an appropriate study design.

OBJECTIVE:

The aim of this study was to systematically review the efficacy and safety of perampanel in the treatment of partial-onset epilepsy.

METHODS:

Electronic and clinical trials databases were searched for RCTs of perampanel published up to March 2013. Outcomes of interest were 50 % responder rates, seizure freedom, treatment-emergent adverse events (TEAEs) and incidence of withdrawal. Meta-analysis was performed to investigate the outcomes of interest.

RESULTS:

Five RCTs with a total of 1,678 subjects were included. The 50 % responder rates were significantly greater in patients receiving 4, 8 and 12 mg perampanel versus placebo, with risk ratios of 1.54 (95 % CI 1.11-2.13), 1.80 (95 % CI 1.38-2.35) and 1.72 (95 % CI 1.17-2.52), respectively. There was no statistical evidence of a difference in seizure freedom between 8 or 12 mg perampanel and placebo. Of the five commonly reported TEAEs included, both dizziness and somnolence were statistically associated with 8 mg perampanel, whilst dizziness was statistically associated with 12 mg perampanel. Incidences of withdrawal due to adverse events were significantly higher in the 8 mg and 12 mg perampanel groups versus placebo.

CONCLUSION:

The use of perampanel resulted in a statistically significant reduction of seizure frequency with respect to the 50 % responder rate in patients with partial-onset epilepsy. Perampanel is well tolerated at 4 mg and reasonably tolerated at 8 and 12 mg. Further clinical and pharmacovigilance studies are required to investigate the long-term efficacy and safety of perampanel in the management of other types of epilepsy.

• Authors: Warrington W Q Hsu, C W Sing, Ying He, Alan J Worsley, Ian C K Wong, Esther W Chan
• Journal: CNS drugs (CNS Drugs) Vol. 27 Issue 10 Pg. 817-27 (Oct 2013) ISSN: 1179-1934 [Electronic] New Zealand
• PMID: 23918722 (Publication Type: Journal Article, Meta-Analysis, Systematic Review)

Chemical References

• Anticonvulsants
• Nitriles
• Pyridones
• perampanel

Topics

• Anticonvulsants (administration & dosage, adverse effects, therapeutic use)
• Databases, Factual
• Dose-Response Relationship, Drug
• Epilepsies, Partial (drug therapy)
• Humans
• Nitriles
• Pyridones (administration & dosage, adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic (methods, statistics & numerical data)
• Research Design
• Treatment Outcome