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Epilepsy Behav. 2016 Oct;63:109-117. doi: 10.1016/j.yebeh.2016.07.018. Epub 2016 Sep 6.

Benzodiazepine use in seizure emergencies: A systematic review.

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Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York City, NY, USA. Electronic address:
Virginia Commonwealth University School of Medicine, Richmond, VA, USA.



The aim of this review was to systematically examine safety and efficacy outcomes, as well as patient/caregiver satisfaction, from clinical studies in pediatric and adult patients treated with benzodiazepines (BZDs) through various administration routes in response to seizure emergencies.


A literature search was conducted to identify articles describing the use of various routes of administration (RoAs) of BZDs for the treatment of seizure emergencies through April 21, 2015, using Embase™ and PubMed®. Eligible studies included (a) randomized controlled trials or (b) controlled nonrandomized clinical trials, either retrospective or prospective. Outcome assessments reviewed were 1) time to administration, 2) time to seizure termination, 3) rate of treatment failure, 4) prevention of seizure recurrence, 5) patient and caregiver treatment satisfaction, 6) adverse events related to BDZ treatment or RoA, and 7) respiratory adverse events.


Seventy-five studies evaluated safety and efficacy using individual or comparator BDZs of various RoAs for treating seizure emergencies in all-aged patients with epilepsy. Buccal, intranasal (IN), or intramuscular (IM) BZDs were often more rapidly administered compared with rectal and intravenous (IV) formulations. Time to seizure termination, seizure recurrence rates, and adverse events were generally similar among RoAs, whereas nonrectal RoAs resulted in greater patient and caregiver satisfaction compared with rectal RoA.


Results of this systematic literature review suggest that nonrectal and non-IV BZD formulations provide equal or improved efficacy and safety outcomes compared with rectal and IV formulations for the treatment of seizure emergencies.


Acute repetitive seizures; Diazepam; Epilepsy; Midazolam; Seizure cluster

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