Efficacy and safety of levetiracetam versus (fos)phenytoin for second-line treatment of epilepticus: a meta-analysis of latest randomized controlled trials. 2021

Yuyi Feng, and Yueyue Chen, and Yaqin Jia, and Zhe Wang, and Xiaoyu Wang, and Lili Jiang, and Chunzhi Ai, and Wei Li, and Yong Liu
School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin 124221, China.

OBJECTIVE To assess the efficiency and safety profiles of levetiracetam and (fos)phenytoin (phenytoin or fosphenytoin) for second-line treatment of seizures by performing a meta-analysis of RCTs. METHODS We systematically searched PubMed, Embase, Cochrane, FDA.gov, and ClinicalTrials.gov for RCTs (published before July 31, 2020; no language restrictions). Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO: CRD42020202736. Eleven studies fulfilled the established criteria. We assessed pooled data by using a random-effects model. Quality analysis was performed by using version 2 of the Cochrane risk-of-bias tool (RoB 2). RevMan v.5.3 was used to perform statistical analyses, and publication bias (egger's test) was assessed with Stata MP v.14.0. RESULTS Levetiracetam was similar to (fos)phenytoin in seizure termination rate (risk ratio [RR] 0.94; 95% CI 0.87 to 1.01), time of seizure termination (mean difference [MD] 0.44; -0.60 to 1.49), and drug resistance ([RR] 1.12, 0.86 to 1.45). The safety outcome showed a significant statistical difference between fosphenytoin group and levetiracetam group ([RR] 1.44, 1.14 to 1.81), while there was no significant difference observed between phenytoin treatment and levetiracetam treatment ([RR] 1.26, 0.99 to 1.60). CONCLUSIONS Levetiracetam was similar to (fos)phenytoin in cessation rate convulsive status epilepticus, and drug resistance, while it was superior (fos)phenytoin in pooled safety outcome. Further exploration is still needed as to whether it is the first choice for second-line drugs.

UI MeSH Term Description Entries
D010672 Phenytoin An anticonvulsant that is used to treat a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. Diphenylhydantoin,Fenitoin,Phenhydan,5,5-Diphenylhydantoin,5,5-diphenylimidazolidine-2,4-dione,Antisacer,Difenin,Dihydan,Dilantin,Epamin,Epanutin,Hydantol,Phenytoin Sodium,Sodium Diphenylhydantoinate,Diphenylhydantoinate, Sodium
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077287 Levetiracetam A pyrrolidinone and acetamide derivative that is used primarily for the treatment of SEIZURES and some movement disorders, and as a nootropic agent. Etiracetam,Etiracetam, (R)-,Etiracetam, R-isomer,Etiracetam, S-isomer,Keppra,UCB 6474,UCB-6474,Ucb L059,Ucb L060,Ucb-L059,Ucb-L060,alpha-ethyl-2-oxo-1-Pyrrolidineacetamide,Etiracetam, R isomer,Etiracetam, S isomer,R-isomer Etiracetam,S-isomer Etiracetam,UCB6474,UcbL060,alpha ethyl 2 oxo 1 Pyrrolidineacetamide
D000927 Anticonvulsants Drugs used to prevent SEIZURES or reduce their severity. Anticonvulsant,Anticonvulsant Drug,Anticonvulsive Agent,Anticonvulsive Drug,Antiepileptic,Antiepileptic Agent,Antiepileptic Agents,Antiepileptic Drug,Anticonvulsant Drugs,Anticonvulsive Agents,Anticonvulsive Drugs,Antiepileptic Drugs,Antiepileptics,Agent, Anticonvulsive,Agent, Antiepileptic,Agents, Anticonvulsive,Agents, Antiepileptic,Drug, Anticonvulsant,Drug, Anticonvulsive,Drug, Antiepileptic,Drugs, Anticonvulsant,Drugs, Anticonvulsive,Drugs, Antiepileptic
D013226 Status Epilepticus A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30) Absence Status,Complex Partial Status Epilepticus,Generalized Convulsive Status Epilepticus,Non-Convulsive Status Epilepticus,Petit Mal Status,Simple Partial Status Epilepticus,Grand Mal Status Epilepticus,Status Epilepticus, Complex Partial,Status Epilepticus, Electrographic,Status Epilepticus, Generalized,Status Epilepticus, Generalized Convulsive,Status Epilepticus, Grand Mal,Status Epilepticus, Non-Convulsive,Status Epilepticus, Simple Partial,Status Epilepticus, Subclinical,Electrographic Status Epilepticus,Generalized Status Epilepticus,Non Convulsive Status Epilepticus,Status Epilepticus, Non Convulsive,Status, Absence,Status, Petit Mal,Subclinical Status Epilepticus
D016032 Randomized Controlled Trials as Topic Works about clinical trials that involve at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. Clinical Trials, Randomized,Controlled Clinical Trials, Randomized,Trials, Randomized Clinical

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