Mechanisms of Levetiracetam in the Control of Status Epilepticus and Epilepsy

Abstract

Status epilepticus (SE) is a major clinical emergency that is associated with high mortality and morbidity. SE causes significant neuronal injury and survivors are at a greater risk of developing acquired epilepsy and other neurological morbidities, including depression and cognitive deficits. Benzodiazepines and some anticonvulsant agents are drugs of choice for initial SE management. Despite their effectiveness, over 40% of SE cases are refractory to the initial treatment with two or more medications. Thus, there is an unmet need of developing newer anti-SE drugs. Levetiracetam (LEV) is a widely prescribed anti-epileptic drug that has been reported to be used in SE cases, especially in benzodiazepine-resistant SE or where phenytoin cannot be used due to allergic side-effects. Levetiracetam’s non-classical anti-epileptic mechanisms of action, favorable pharmacokinetic profile, general lack of central depressant effects, and lower incidence of drug interactions contribute to its use in SE management. This review will focus on LEV’s unique mechanism of action that makes it a viable candidate for SE treatment.

Early enteral levetiracetam in diazepam‐resistant convulsive status epilepticus

“…9 In the present study, ivDZP plus ngLEV combined therapy was effective for adult CSE patients for controlling ongoing seizures, even when initial emergent treatment with diazepam failed. The present results (88.9%) are more favorable than those of a recent meta-analysis (56.2-78.7%) in patients with benzodiazepine-resistant CSE.…”

“…Two of the 21 (9.5%) patients had acute symptomatic seizures caused by acute cerebral infarction. The overall mean Glasgow Coma Scale score just before treatment was 8 AE 3 (range [3][4][5][6][7][8][9][10][11][12], and the duration from seizure onset to ivDZP was 69 AE 43 min (range 12-145 min). No enrolled CSE patients in the present study required intubation for respiratory care.…”

“…8 Levetiracetam (LEV) is a newer AED with a low incidence of side-effects and multiple mechanisms of action that differentiate it from conventional AED. 9 Intravenous LEV is equally effective as lorazepam, as both emergent initial (76.3 vs 75.6%) and urgent control (79.3 vs 67.7%) therapy for convulsive SE (CSE), without significant side-effects; 10 even in cases of convulsive benzodiazepineresistant SE, the estimated efficacy of levetiracetam is 68.5%. 11 In addition, a previous retrospective study suggested that LEV administration through a nasogastric tube (ngLEV) might be a useful alternative for controlling SE seizures if given early.…”

Novel contribution in online sample cleanup for quantitative determination of Levetiracetam in human plasma by LC-Tandem mass spectrometry

“…Levetiracetam effecttively used for other psychiatric and neurologic symptoms such as Tourette syndrome, autism, as well as anxiety disorders. At present, little is known concerning the mechanism of antiepileptic action [6]. Numerous chromatographic methods have been described for the quantification of LEV in biological fluids.…”

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“…Reports showing the use of LEV to correct deficits in learning and memory in an Alzheimer's mouse model and its favourable pharmacokinetic parameters including faster absorption, negligible binding to plasma proteins, lack of enzyme induction, absence of interactions with other drugs, and restricted metabolism outside the liver were considered as the rationale for its selection into this study 13,14 . Based on the above findings of literature, this study aims to evaluate the extent of aggravation of memory impairment (MI) induced by VAL at normal and reduced doses when administered alone and in combination with LEV on temporal lobe epileptic mice.…”