Alexandra Santana Almansa, Jessica R Landers, Nicholas S Abend, Giulia M Benedetti, Catherine J Chu, Andrew T Knox, Shavonne Massey, Steffany Moen, Andrea C Pardo, Arnold Sansevere, Renée A Shellhaas, Cameron Thomas, Tammy Tsuchida, Sonya Wang, Bo Zhang, Janet S Soul
Among 62 eligible neonates, 33 had acute provoked seizures while 29 had neonatal-onset epilepsy; there was no difference in seizure type or baseline seizure severity between groups. There were high rates of pretreatment status epilepticus (48%) and treatment-resistant seizures, with 93% receiving ≥ 3 ASMs before lacosamide. Most received intravenous lacosamide, with a median loading dose of 5.0 mg/kg and median daily dose of 7.3 mg/kg. Seizure cessation occurred in 37% of neonates; 21% had no additional ASM administered after lacosamide. Seizure burden, measured in seizure minutes per hour, was lower at both 4 h and 7 days following lacosamide administration. In addition, there was a median reduction in seizure frequency of 30 seizures per day at 7 and 30 days posttreatment (p < .05). Lacosamide was continued at discharge in most neonates (72%). Seventy adverse events were reported in 35 (56%) neonates. Four transient events with possible or unknown relationship to lacosamide were likely multifactorial in origin; none were cardiac arrhythmias.
OBJECTIVE: Most antiseizure medications (ASMs) are prescribed off label for neonates. Lacosamide's efficacy in infants and availability in intravenous formulation suggest potential utility for neonates. We evaluated the safety and efficacy of lacosamide for neonatal seizures.
METHODS: This 10-center, retrospective study of neonates with seizures and lacosamide treatment initiated by ≤ 48 weeks postmenstrual age collected clinical data from medical records and electroencephalogram recordings. Lacosamide efficacy was determined by changes in seizure burden with lacosamide treatment and seizure cessation by hospital discharge. Potential adverse events were reviewed.
RESULTS: Among 62 eligible neonates, 33 had acute provoked seizures while 29 had neonatal-onset epilepsy; there was no difference in seizure type or baseline seizure severity between groups. There were high rates of pretreatment status epilepticus (48%) and treatment-resistant seizures, with 93% receiving ≥ 3 ASMs before lacosamide. Most received intravenous lacosamide, with a median loading dose of 5.0 mg/kg and median daily dose of 7.3 mg/kg. Seizure cessation occurred in 37% of neonates; 21% had no additional ASM administered after lacosamide. Seizure burden, measured in seizure minutes per hour, was lower at both 4 h and 7 days following lacosamide administration. In addition, there was a median reduction in seizure frequency of 30 seizures per day at 7 and 30 days posttreatment (p < .05). Lacosamide was continued at discharge in most neonates (72%). Seventy adverse events were reported in 35 (56%) neonates. Four transient events with possible or unknown relationship to lacosamide were likely multifactorial in origin; none were cardiac arrhythmias.
SUMMARY: Despite high rates of treatment-resistant seizures in this neonatal cohort, 37% experienced seizure cessation and most remained on lacosamide at hospital discharge. Most adverse events were not attributed to lacosamide. These results favor use of lacosamide and provide a rationale for future prospective studies.