Levetiracetam for epilepsy: an evidence map of efficacy, safety and economic profiles

Abstract

ObjectiveTo evaluate the efficacy, safety and economics of levetiracetam (LEV) for epilepsy.Materials and methodsPubMed, Scopus, the Cochrane Library, OpenGrey.eu and ClinicalTrials.gov were searched for systematic reviews (SRs), meta-analyses, randomized controlled trials (RCTs), observational studies, case reports and economic studies published from January 2007 to April 2018. We used a bubble plot to graphically display information of included studies and conducted meta-analyses to quantitatively synthesize the evidence.ResultsA total of 14,803 records were obtained. We included 30 SRs/meta-analyses, 34 RCTs, 18 observational studies, 58 case reports and 2 economic studies after the screening process. The included SRs enrolled patients with pediatric epilepsy, epilepsy in pregnancy, focal epilepsy, generalized epilepsy and refractory focal epilepsy. Meta-analysis of the included RCTs indicated that LEV was as effective as carbamazepine (CBZ; treatment for 6 months: 58.9% vs 64.8%, OR=0.76, 95% CI: 0.50–1.16; 12 months: 54.9% vs 55.5%, OR=1.24, 95% CI: 0.79–1.93), oxcarbazepine (57.7% vs 59.8%, OR=1.34, 95% CI: 0.34–5.23), phenobarbital (50.0% vs 50.9%, OR=1.20, 95% CI: 0.51–2.82) and lamotrigine (LTG; 61.5% vs 57.7%, OR=1.22, 95% CI: 0.90–1.66). SRs and observational studies indicated a low malformation rate and intrauterine death rate for pregnant women, as well as low risk of cognitive side effects. But psychiatric and behavioral side effects could not be ruled out. LEV decreased discontinuation due to adverse events compared with CBZ (OR=0.52, 95% CI: 0.41–0.65), while no difference was found when LEV was compared with placebo and LTG. Two cost-effectiveness evaluations for refractory epilepsy with decision-tree model showed US$ 76.18 per seizure-free day gained in Canada and US$ 44 per seizure-free day gained in Korea.ConclusionLEV is as effective as CBZ, oxcarbazepine, phenobarbital and LTG and has an advantage for pregnant women and in cognitive functions. Limited evidence supports its cost-effectiveness.Registered numberPROSPERO (No CRD 42017069367).

Levetiracetam and Memory Loss

“…The research nullifies the hypothesis that Levetiracetam are (or can be) associated with memory loss in children or adults. Moreover, the study discovers that Levetiracetam is related to an increase in cognitive functions and has an advantage for pregnant women (Yi et al, 2018).…”

“…Besides, the findings were consistent among the children with developing delay, brain malformations, an inborn error of breakdown, as Levetiracetam was discovered to effective in reducing the epileptiform EEG abnormalities. Levetiracetam result in improved cognitive functions, behavior, safety, tolerability, and efficacy especially in children aged between four to fourteen years of age as recorded by Yi, Wen, Cai, Xu, Zhong, Zhan, and Zhai (2018). Cognition and behavior in children are effectively measured using the Leiter-R International Performance Scale for a period of forty-eight non-comparable weeks.…”

“…The research indicates toleration of the drug with minor side effects such as headache, aggression, and irritability. Despite a small portion of the sample leaving the investigation due to the adverse impacts of the drug, Levetiracetam offers good seizure control with a quarter of the sample size reporting complete freedom from all seizures (Yi et al, 2018). Besides, Levetiracetam is associated with improved cognitive functioning as well as improved emotional behavior of children.…”

“…The article recognizes the effectiveness and efficiency of the drug as it is easily absorbed and does not affect the absorption of food as it is administered orally. Levetiracetam rare adverse effects according to Yi, Wen, Cai, Xu, Zhong, Zhan, and Zhai (2018) include reduced sperm quality and elevated kinase as well as general nausea, irritability, and aggressiveness. Apart from these effects, Levetiracetam is not associated with other effects such as memory loss and therefore disqualifies the hypothesis.…”

Efficacy, Safety, and Economics of Intravenous Levetiracetam for Status Epilepticus: A Systematic Review and Meta-Analysis

“…No clinically significant interactions with other AEDs were found since LEV is mainly renal excreted unchanged independent of liver cytochrome P450 (Emswiler and Cumpston, 2017) Compared to many other AEDs, LEV had fewer reported adverse events (AEs), but this may be because of its relatively short period of clinical use (Trinka and Dobesberger, 2009;Trinka, 2011). In recent years, apart from psychiatric and behavioral side effects (Yi et al, 2018), some rare AEs of LEV including rhabdomyolysis, thrombocytopenia and anaphylaxis were reported (Koklu et al, 2014;Di Lorenzo and Li, 2017;Kim and Shin, 2017).…”