Meta-Analysis of Randomized Trials on First Line and Adjunctive Levetiracetam

Abstract

Levetiracetam, a pyrrolidine, the racemically pure Senantiomer of pyrrolidineacetamide, is an antiepileptic medication with a novel mechanism, related to a specific binding site in the brain for the synaptic vesicle protein 2A 1 . In contrast to the mechanism of traditional antiepileptics, there is no evidence for action on voltage-gated sodium channel, gammaamino butyric acid, or glutamate-mediated synaptic transmission 2 . Levetiracetam has a linear pharmacokinetic profile, high oral bioavailability (close to 100%), and is not bound to proteins, with 95% being metabolized and excreted in urine 3 . Plasma concentrations peak within one hour, with steady- épilepsie réfractaire au traitement, 1 comme médicament de première intention chez des patients au moment du diagnostic de l'épilepsie et 1 comme monothérapie en prophylaxie. Huit des essais cliniques randomisés évaluant le lévétiracétam comme médicament d'appoint étaient de qualité moyenne (critères GRADE), dont 2 où le traitement n'était pas en aveugle. Les méta-analyses ont montré que le lévétiracétam comme traitement d'appoint était plus efficace que le placebo pour diminuer d'au moins 50% la fréquence des crises quand il était ajouté au régime posologique de base (RR global 2,15 [1,82] ; 12 = 45%, p (hétérogénéité) = 0,08 ; p effet global < 0,01). La probabilité que des incidents thérapeutiques sérieux entraînent le retrait du patient de l'étude n'était pas significativement différente entre le groupe recevant le lévétiracétam et le groupe témoin (RR global 1,37 [0,13] ; 12 = 0% ; p (hétérogénéité) = 0,84 ; p effet global = 0,17). Selon les analyses de sous-groupes, les effets seraient les mêmes, quelle que soit la posologie. Les analyses de sensibilité des études bien menées à l'insu ont montré des effets similaires. Conclusions : Le lévétiracétam est un médicament d'appoint efficace dans l'épilepsie réfractaire au traitement. Il devra faire l'objet de nouvelles études pour établir son efficacité en monothérapie chez les patients dont le diagnostic est récent et en prophylaxie chez les patients qui ont subi un traumatisme crânien. common side effects of levetiracetam include somnolence, asthenia and dizziness 5 . Meta-analysis suggests that the extended release version of this medication, when compared to placebo, may be associated with lower incidence of nervous system, psychiatric, nutritional and metabolic adverse effects 2-5 . So far, only four systematic reviews 2-5 have been conducted verifying its efficacy as a sole agent in refractory partial-onset seizures, as well as adjunctive agent in epilepsy. These studies were limited by lack of clarity in selection criteria, exclusion of potentially relevant trials, lack of critical appraisal of primary studies, and for-profit funding of most trials. OBJECTIVESThe purpose of this review and meta-analysis is to systematically collect, critically appraise, and synthesize current evidence regarding the efficacy and tolerability of levetiracetam as a first line or adjunctive agent for adults suffering from i...

The adverse event profile of levetiracetam: A meta-analysis on children and adults

“…Lo BW et al [22] performed another meta-analysis of 10 RCTs: the likelihood of serious AEs requiring withdrawal from the study was not significantly different between LEV patients and controls (RR= 1.37; 95% CIs 0.88 to 2.13). The meta-analysis of Zaccara et al [51] was performed on 5 RCTs and found only somnolence being associated with LEV (RD 0.07; 95% CIs 0.01 to 0.12).…”

“…Different randomized controlled trials (RCTs) and some meta-analyses [22,24,26] have shown a good safety profile for this drug.…”

Measurement of levetiracetam drug levels to assist with seizure control and monitoring of drug interactions with other anti-epileptic medications (AEMs)

“…LEV is considered to be an effective add-on treatment across various seizure types in patients with refractory epilepsy. 25 The PWE in this study were prescribed LEV as adjunctive treatment and converted to monotherapy when possible. LEV monotherapy, monitored with blood levels, was more effective than was LEV with polypharmacy and demonstrated reduced concentration/dose ratio.…”

An update of the Hong Kong Epilepsy Guideline: consensus statement on the use of antiepileptic drugs in Hong Kong

“…In paediatric cohorts, the proportion of such adverse events was 20% to 30%. [70][71][72]94 By comparison, the behavioural sideeffects in adults were less prominent.…”