Changes in Real-world Practice Patterns of Antiepileptic Drugs for Status Epilepticus: A Nationwide Observational Study in Japan

Intravenous (i.v.) phenytoin/fosphenytoin is recommended as the second-line therapy of antiepileptic drugs in patients with status epilepticus (SE). i.v. Levetiracetam is regarded as an effective and safe equivalent with i.v. phenytoin/fosphenytoin. However, i.v. levetiracetam is not covered by public health insurance for SE in most countries. For this study, we performed the real-world practice pattern survey of antiepileptic drugs for status epilepticus using the nationwide inpatient database. We used the Japanese Diagnosis Procedure Combination inpatient database in Japan and identified all cases of emergency admission attributable to status epilepticus from March 2011 through March 2018. We described the patient characteristics and practice pattern of antiepileptic drugs. The analysis conducted for this study examined 31,472 cases. As the second-line therapy, the use of i.v. levetiracetam increased rapidly from 2016; 35% of cases received i.v. levetiracetam in 2017. By contrast, the use of i.v. phenytoin/fosphenytoin decreased from 2016. In-hospital mortality decreased year-by-year. No year-by-year change was observed for deaths within 24 h, length of hospital stay, drug-induced hepatitis, or drug-induced eruption. Although the use of levetiracetam for treatment of SE is not compensated by public health insurance in Japan, i.v. levetiracetam use is increasing dramatically as the second-line SE therapy. We propose that health insurance coverage be extended to include i.v. levetiracetam treatment for SE.