IV Lacosamide Effective as Acute Treatment of Status Epilepticus
VANCOUVER, BC—Use of lacosamide as the last antiepileptic drug (AED) a patient is administered for status epilepticus (SE) is "strongly associated with termination of status," authors of a retrospective study reported at the 68th AAN Annual Meeting.
"We found that both the number of AEDs and time to start of lacosamide were significantly and inversely associated with termination of seizures, whereas the age of the patient did not play a significant role," Hardik Doshi, MD, from the Department of Neurology at Wayne State University, Detroit, MI, and study coauthors reported.
Standard initial treatment of SE, a neurological emergency with a high rate of morbidity and mortality, is with a benzodiazepine, followed by traditional AEDs such as phenytoin and valproic acid. Lacosamide, a newer AED, "has better tolerability, lack of drug-drug interactions, and ease of use," the authors noted. "It has been shown to quickly cross the blood-brain barrier in intravenous solution."
However, to date, evidence for efficacy of using lacosamide to terminate SE "is limited to small case series," they pointed out.
To determine the agent's effect on SE, the investigators conducted a retrospective single-institution chart review for patients with SE who were administered lacosamide between December 1, 2010, through October 31, 2014.
Patients were included if they had received intravenous lacosamide 200mg to 600mg and had SE, which was "defined as clinical seizures without return to baseline or electrographic seizures lasting more than 5 minutes," Dr. Doshi noted.
The data collected included age, sex, race, type of SE, history of epilepsy, baseline AEDs, SE etiology, the order and loading doses of AEDs given, including time of medication from treatment initiation, and SE termination, defined "clinically or electrographically without recurrence within 24 hours," they reported.
A total of 117 patients were found to have been treated with intravenous lacosamide for SE. Average age was 58 years (range, 21–98 years); 70.9% were African American and 72 were women. Among these patients, 49.6% had a history of epilepsy and 17.9%, a history of SE. Types of SE were generalized convulsive in 44.4%, focal motor in 29.1%, and non-convulsive in 26.5%. The etiology of SE was structural in 32.5% and non-lesional in 67.5%.
When first-line treatment for SE was examined, the authors found that 76.9% had received a benzodiazepine; 12.8%, lacosamide; 6.0%, phenytoin; and 4.3%, another AED. The average total number of AEDs used in treatment was 3.
The average time from use of first agent to lacosamide loading dose was 23.6 hours (median, 5.5 hours; range, 0–219 hours). Lacosamide sequence in treatment was first in 10.3% of cases (no benzodiazepine was given), second in 40.2%, third in 27.4%, fourth in 12%, and fifth onward in 10.3%.
Results showed that 72 patients had termination of SE within 24 hours of lacosamide loading dose; 45 patients had refractory SE more than 24 hours after lacosamide administration.
In those whose SE terminated within 24 hours, lacosamide was the last agent used in 62 patients (86%), whereas in those who remained in SE after 24 hours, lacosamide was the last agent used in 28 (62%; P=0.003).
Of the cases with lacosamide as the last agent (90/117), 69% had SE termination and 31% continued to be in SE.
As noted, the number of AEDs (OR 0.69; P=0.042) and time to start of lacosamide (OR 0.98; P=0.037) were significantly and inversely associated with SE termination; however, patient age did not play a role (OR 1.01; P=0.538).
After correcting for the above confounders, "use of lacosamide as the last agent remained strongly associated with termination of status (OR 2.95; P=0.03)."
"Our study suggests lacosamide may be an effective option in the treatment of SE," Dr. Doshi noted, and that the agent "is more effective when administered earlier in management of SE."
The failure of lacosamide to terminate SE when used later "may reflect the super-refractory nature of SE rather than loss of efficacy," he added.
No adverse events were reported, "indicating lacosamide as a potentially safe and highly tolerable option," the authors concluded.
Prospective controlled trials are needed to identify the efficacy and tolerability of lacosamide for SE.