Levetiracetam for the treatment of status epilepticus

Abstract

Status epilepticus (SE) is a common, severe neurological disorder, and prolonged seizures in SE may result in irreversible brain damage in association with high disability and mortality rates. Thus, termination of seizures as soon as possible is vital for the successful treatment of this disease. Levetiracetam, a new broad-spectrum anti-epileptic drug, can be used to rapidly and effectively control SE episodes with few side effects. Thus, an understanding of the use of this drug to treat SE will help clinicians to more effectively control SE and improve patient prognosis.

Keywords:

• epilepsy
• levetiracetam
• prognosis
• seizure
• status epilepticus

Financial & competing interests disclosure

This work was supported by the National Clinical Key Specialty Construction Foundation of China and the National Natural Science Foundation of China (grant number 81271445). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Status epilepticus (SE) is a common neurological emergency associated with high morbidity and mortality rates. The selection of anti-epileptic drugs (AEDs) with rapid onset of action, high levels of safety and high efficacies for the control of seizures is essential for the successful treatment of SE. Levetiracetam (LEV), a new AED, causes few mild side effects and may represent a new alternative to traditional AEDs.

• The anti-convulsant effect and safety of LEV have been confirmed in animal experiments, and its use for the treatment of SE has been supported by the European Society for Neuroscience and Italian Antiepileptic Association.

• The results of many clinical research studies and evidence-based medical studies support the use of LEV in combination with traditional AEDs as a safe and effective treatment for controlling SE seizures.

• LEV exerts an anti-convulsant effect via a different mechanism compared with other AEDs. It also plays a neuroprotective role in reducing SE-induced neuronal injury. Its high permeability, low protein binding rate and short peak time enable it to rapidly penetrate the blood–brain barrier and exert its anti-epileptic effects. In addition, its hydrolysis and metabolism are not dependent on liver cytochrome P450, and it has few interactions with other AEDs due to its pharmacokinetic features.

• This review summarizes previous reports of the use of LEV for the treatment of SE, addressing the following aspects: symptoms, administration, dosage, onset time, adverse reactions and precautions.

• An ongoing prospective, multicenter, randomized, double-blind, Bayesian adaptive, Phase III comparative effectiveness trial being conducted by Bleck [74] may provide a new strategy for the treatment of SE, particularly in patients of different ages, and facilitate the selection of more safe and effective drugs.

• Future studies of the use of LEV to treat SE may involve the use of LEV in the rationalization of SE and the development of an LEV combination therapy. Such investigations should have a larger sample size and include reasonable prospective clinical control studies.

• With continuous advances in technology to promote the sharing of medical information and increasing studies of the use of LEV to treat SE, a larger sample size of SE patients can be used to standardize and rationalize the administration of LEV for seizure termination and to develop a new strategy to improve the survival and prognosis of SE patients.