<p>A meta-analysis of levetiracetam for randomized placebo-controlled trials in patients with refractory epilepsy</p>

Abstract

Objective The objective of this study was to investigate the efficacy and safety profile of levetiracetam as add-on therapy in patients with refractory epilepsy. Methods Web of Science, MEDLINE (Ovid and PubMed), Cochrane Library, EMBASE, and Google Scholar were systematically searched to identify potential eligible randomized controlled trials by two reviewers independently. Pooled estimates of risk ratios (RRs) for 50%, 75%, and 100% reduction from baseline were calculated using the fixed-effect model or random-effect model. Quality of included studies was assessed with the Cochrane Collaboration’s Risk of Bias tool. Serious adverse events and withdrawals induced by interventions and the most common side effects were analyzed. Results Seventeen trials with a total of 3,205 participants were included in this meta-analysis, including 14 trials for adulthood and three trials for children. Pooled estimates suggested that levetiracetam was an effective anti-epileptic drug at 1,000–3,000 mg/day (RR =2.00 for 1,000 mg/day, RR =2.68 for 2,000 mg/day, RR =2.18 for 3,000 mg/day) for adults and 60 mg/kg/day (RR =2.00) for children compared to placebo in terms of 50% reduction from baseline. Likewise, as for seizure freedom rate, levetiracetam had an advantage over placebo at 1,000–3,000 mg/day (RR =5.84 for 1,000 mg/day, RR =4.55 for 2,000 mg/day, RR =4.57 for 3,000 mg/day, respectively) for adults and 60 mg/kg/day (RR =4.52) for children. Regarding safety profile, patients treated with levetiracetam had significantly higher occurrence than placebo for somnolence, asthenia, dizziness, infection, nasopharyngitis, anxiety, and irritability; however, most studies reported that these adverse events were mild and transient. Conclusion Levetiracetam is an effective anti-epileptic drug for both adults and children with generalized or partial-onset refractory seizures at 1,000–3,000 or 60 mg/kg/day, with a favorable adverse event profile.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy

“…There was a 75% reduction in seizures through using LEV, with similar results for doses of 2,000 and 3,000 mg. The safety of LEV was comparable to that of placebo 7 .…”

“…It is recommended as a first-line add-on agent for focal seizures and, additionally, has a favorable pharmacokinetic profile. Studies have shown that LEV is an effective anti-seizure medication for both adults and children with generalized or focal-onset refractory seizures, at doses of 1,000-3,000 mg/day or 60 mg/kg/day, with an acceptable adverse event profile 7 . However, little information about LEV use in the Brazilian population is available.…”

Integration of postmortem amygdala expression profiling, GWAS, and functional cell culture assays: neuroticism-associated synaptic vesicle glycoprotein 2A (SV2A) gene is regulated by miR-133a and miR-218

“…Humans have higher levels of SV2A in the amygdala than in other tissues, based on genome-wide expression profiling data 61,62 . SV2A is the binding site of the anticonvulsant drug levetiracetam ((S)-α-Ethyl-2-oxo-1-pyrrolidineacetamide) 52 , which has shown promise in anxiety disorder treatment [63][64][65][66][67][68][69] , but also generates states of anxiety as a side-effect in some individuals 70,71 . Such individual differences may reflect underlying genetic variations, which is very plausible, given that multiple SV2A SNPs are associated with anxiety by GWAS.…”

Safety and Efficacy of Brivaracetam in Pediatric Refractory Epilepsy: A Single-Center Clinical Experience

“…6 Levetiracetam is the most widely used antiepileptic drug in the United States, in large part because of its efficacy and generally favorable safety profile. 11 A recent meta-analysis by Cao et al 12 showed a positive response, with greater than 50% reduction in seizure or seizure freedom in children who use levetiracetam as adjunctive therapy for focal epilepsy compared to placebo. However, a Cochrane Review by Mbizvo et al 10 found the rate of behavioral side effects in children treated with levetiracetam to be as high as 23%.…”