OBJECTIVES: To systematically examine efficacy and patient/caregiver satisfaction outcomes in the treatment of seizure emergencies. Data included in this review are from clinical studies in pediatric and adult patients treated with benzodiazepines (BZDs) through various routes of administration (RoA). METHODS: Literature searches using Embase^TM and PubMed^®were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included (a) randomized controlled or (b) controlled, non-randomized clinical trials. Clinical pharmacology studies, case studies, and studies examining patients with refractory status epilepticus or psychogenic non-epileptic seizures were excluded. Outcome assessments reviewed included 1) time to administration, 2) time to seizure termination, 3) rate of treatment failure within 10 mins post-treatment, 4) rate of seizure recurrence up to 1 and 12 hours post-treatment, and 5) patient and caregiver treatment satisfaction. RESULTS: Searches identified 1170 non-duplicate articles. Overall, 75 unique studies met eligibility criteria; of these, time to administration was reported in 13 publications, time to seizure termination in 36, rate of treatment failure in 37, rate of seizure recurrence in 25, and patient and caregiver satisfaction in 12. In general, benzodiazepines were more rapidly administered when using non-rectal and non-intravenous (IV) RoA. For example, buccal, intranasal, or intramuscular benzodiazepines were administered 0.2 – 10.7 min faster than IV or rectal benzodiazepines in 9 studies; only 3 studies reported no difference in time to administration. In contrast, time to seizure termination, rate of treatment failure, and rate of seizure recurrence were generally similar among all RoA. In regards to caregiver and patient satisfaction, non-rectal RoA was generally preferred versus rectal RoA. CONCLUSIONS: Results of this systematic literature review suggest that non-rectal and non-IV BZD formulations provide equal efficacy and improved treatment satisfaction compared with rectal and IV formulations for the treatment of seizure emergencies. Support: Upsher-Smith Laboratories, Inc.