Outpatient pharmacotherapy and modes of administration for acute repetitive and prolonged seizures

Acute repetitive seizures (ARS) are a serious epilepsy phenomenon, generally described as closely grouped seizures over minutes to 2 days, representing an increase in seizure frequency compared with baseline. In some instances, ARS may not stop without treatment, and evolution into status epilepticus is a significant concern. Additionally, neuronal injury may occur after even brief repeated seizures. Given the substantial risks that may be involved with ARS, it is crucial to develop appropriate protocols for identification and management of this seizure phenomenon. This article focuses on pharmacotherapy and, in particular, different modes of administering medication for ARS in the outpatient setting. Our aim was to present a review of data from non-randomized and randomized, controlled trials to evaluate the efficacy, safety and tolerability of out-of-hospital ARS treatments. Several of the studies included patients with ARS, as well as patients with prolonged seizures. Prolonged seizures, or seizures lasting greater than 5 min, have similar risks and treatment options to those of ARS; therefore, this discussion also includes treatment trials and recommendations for prolonged seizures. All trials used benzodiazepines, a class of drugs that are ideal for the ARS and prolonged seizure populations because of their rapid onset of action and minimal adverse effects. Rectal diazepam is currently the only formulation approved by the US Food and Drug Administration (FDA) for out-of-hospital treatment. Oral benzodiazepines are appropriate only for mild ARS. Intramuscular diazepam autoinjection has shown success against ARS in clinical trials. Intranasal midazolam and diazepam are in testing. Other treatments have also been explored--specifically, buccal midazolam (approved in the European Union), sublingual lorazepam and intranasal lorazepam.