The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: A meta-analysis of published studies

PURPOSE Systematic evaluation of published evidence-base of the efficacy of five antiepileptic drugs - lacosamide, levetiracetam, valproate, phenytoin and phenobarbital - in convulsive benzodiazepine-resistant status epilepticus. METHODS Data sources included electronic databases, personal communication, and back tracing of references in pertinent studies. These were prospective and retrospective human studies presenting original data for participants with convulsive benzodiazepine-resistant status epilepticus. Interventions were intravenous lacosamide, levetiracetam, phenobarbital, phenytoin and valproate. Outcome measured is clinically detectable cessation of seizure activity. Level-of-evidence was assessed according to Oxford Centre of Evidence-Based Medicine and The Cochrane Collaboration's Tool for Assessment of Risk. Twenty seven studies (798 cases of convulsive status epilepticus) were identified and 22 included in a meta-analysis. Random-effects analysis of dichotomous outcome of a single group estimate (proportion), with inverse variance weighting, was implemented. Several sources of clinical and methodological heterogeneity were identified. RESULTS Efficacy of levetiracetam was 68.5% (95% CI: 56.2-78.7%), phenobarbital 73.6% (95% CI: 58.3-84.8%), phenytoin 50.2% (95% CI: 34.2-66.1%) and valproate 75.7% (95% CI: 63.7-84.8%). Lacosamide studies were excluded from the meta-analysis due to insufficient data. CONCLUSION Valproate, levetiracetam and phenobarbital can all be used as first line therapy in benzodiazepine-resistant status epilepticus. The evidence does not support the first-line use of phenytoin. There is not enough evidence to support the routine use of lacosamide. Randomized controlled trials are urgently needed.