Updated review of rescue treatments for seizure clusters and prolonged seizures

ABSTRACT

Introduction

Although the treatment of epilepsy primarily focuses on prevention, recurrent seizures are unfortunately an ongoing reality, particularly in people with epilepsy who live with chronic refractory seizures. Rescue medications are agents which can be administered in urgent/emergent seizure episodes such as seizure clusters or prolonged seizures with the goal of terminating seizure activity, preventing morbidity, and decreasing the risk of further seizures.

Areas covered

This review first discusses clinical opportunities for rescue medications, with particular attention focused on seizure clusters and prolonged seizures, including their epidemiology, risk factors, and associated morbidity. Current rescue medications, their indications, efficacy, and adverse effects are discussed. We then discuss rescue medications and formulations which are currently under development, concentrating on practical aspects relevant for clinical care.

Expert opinion

Rescue medications should be considered for all people with epilepsy with ongoing seizures. Recent rescue medications including intranasal formulations provide considerable advantages. New rescue medications are being developed which may expand opportunities for effective treatment. In the future, combining rescue medications with seizure detection and seizure prediction technologies should further expand opportunities for use and should reduce the morbidity of seizures and provide increased comfort, control, and quality of life for people living with epilepsy.

KEYWORDS:

• Acute repetitive seizures
• diazepam
• epilepsy
• intranasal
• midazolam
• rescue medication
• prolonged seizures
• seizure clusters
• nasal
• benzodiazepines
• buccal
• intramuscular
• inhalational

Article highlights

• Rescue medications are agents which can be administered in urgent/emergent seizure episodes such as seizure clusters or prolonged seizures with the goal of terminating seizure activity, preventing morbidity, and decreasing the risk of recurrence.

• Seizure clusters are associated with overall epilepsy severity, including seizure frequency, drug-resistant epilepsy, and status epilepticus

• Seizure clusters are very common in people with active epilepsy, including those who do not report prior clusters, and are associated with increased morbidity

• In addition to use for seizure clusters (on-label), rescue medications are commonly prescribed for prolonged seizures (usually off-label)

• Timely administration of benzodiazepines has clear benefits for reducing morbidity in the setting of convulsive status epilepticus; rescue medication use outside of the hospital may serve as an early treatment of status epilepticus or to prevent progression to status epilepticus

• Currently FDA approved rescue medications include rectal diazepam and intranasal midazolam and diazepam

• The intranasal rescue medications have several advantages over rectal formulation

• New rescue medications are being developed with intrapulmonary (inhalational), buccal (already approved in several countries but not in the United States), and intramuscular routes of administration

• Neurostimulation systems can be used as rescue therapy

• Combining seizure detection and prediction technologies with the use of rescue medication will be an important advance in epilepsy treatment

Declaration of interest

L J Hirsch has received consultation fees for advising from Accure, Aquestive, Ceribell, Eisai, Marinus, Medtronic, Neurelis, Neuropace and UCB Pharma.; Royalties from Wolters–Kluwer for authoring chapters for UpToDate-Neurology, and from Wiley for co-authoring the book Atlas of EEG in Critical Care; and honoraria for speaking or running webinars from Neuropace, Natus, and UCB Pharma. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.