Efficacy of nonvenous medications for acute convulsive seizures: A network meta-analysis.
OBJECTIVE
This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus.


METHODS
Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking.


RESULTS
This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network.


CONCLUSIONS
Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA. Ravindra.Arya@cchmc.org.
Ravindra
R
Arya
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Harsh
H
Kothari
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Zongjun
Z
Zhang
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Baoguang
B
Han
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Paul S
PS
Horn
From the Comprehensive Epilepsy Center, Division of Neurology (R.A., P.S.H., T.A.G.), and the Division of Epidemiology and Biostatistics (P.S.H.), Cincinnati Children's Hospital Medical Center, OH; the Department of Pediatrics (H.K.), The Unterberg Children's Hospital at Monmouth Medical Center, Long Branch, NJ; the Department of Mathematical Sciences (Z.Z.), University of Cincinnati, OH; and Biogen (B.H.), Cambridge, MA.
Tracy A
TA
Glauser
D000208:Acute Disease; D000927:Anticonvulsants / Q000008:administration & dosage*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D012640:Seizures / Q000175:diagnosis* / Q000188:drug therapy*; D016896:Treatment Outcome
D000927:Anticonvulsants