Treatment of Seizure Clusters in Epilepsy: A Narrative Review on Rescue Therapies

Abstract

Epilepsy is a common neurological disorder in the United States, affecting approximately 1.2% of the population. Some people with epilepsy may experience seizure clusters, which are acute repetitive seizures that differ from the person’s usual seizure pattern. Seizure clusters are unpredictable, are emotionally burdensome to patients and caregivers (including care partners), and require prompt treatment to prevent progression to serious outcomes, including status epilepticus and associated morbidity (e.g., lacerations, fractures due to falls) and mortality. Rescue medications for community use can be administered to terminate a seizure cluster, and benzodiazepines are the cornerstone of rescue treatment. Despite the effectiveness of benzodiazepines and the importance of a rapid treatment approach, as many as 80% of adult patients do not use rescue medication to treat seizure clusters. This narrative review provides an update on rescue medications used for treatment of seizure clusters, with an emphasis on clinical development and study programs for diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. Results from long-term clinical trials have shown that treatments for seizure clusters are effective. Intranasal benzodiazepines provide ease of use and patient and caregiver satisfaction in pediatric and adult patients. Adverse events attributed to acute rescue treatments have been characterized as mild to moderate, and no reports of respiratory depression have been attributed to treatment in long-term safety studies. The implementation of an acute seizure action plan to facilitate optimal use of rescue medications provides an opportunity for improved management of seizure clusters, allowing those affected to resume normal daily activities more quickly. Some people with epilepsy who take antiseizure medications may still have seizures. These seizures might happen in clusters. Seizure clusters are emergencies that need to be treated quickly to lower the risk of status epilepticus and hospitalization. Also, these clusters can be stressful. Approved rescue medications are diazepam rectal gel, midazolam nasal spray, and diazepam nasal spray. They can all be used by family and other caregivers, and nasal sprays may be preferred in a public setting. All of these treatments can be used for adults, but each has a different age limit for children. Overall, these therapies are underused; however, all have been shown to work in stopping seizure clusters and have mild to moderate side effects. Nasal treatments offer ease of use and satisfaction for patients and caregivers (care partners). However, data for some effects and patient groups are not available for all treatments. Seizure action plans are designed to give step-by-step instructions about when and how to use rescue medication. Increased use of action plans may improve at-home treatment of seizure clusters and allow patients to perform their normal daily activities and avoid injury or hospitalizations.

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