Abstracts

Rationale: Lacosamide (LAC) is a novel adjunctive agent for partial seizures available in the U.S. since June 2009. The medication appears to be an ideal anti-epileptic drug (AED) for use in critically ill patients given its availability in dose equivalent oral and intravenous (IV) formulations, lack of hepatic cytochrome P450 isoenzyme induction, and minimal drug-drug interaction. We report our initial experience with LAC in critically ill patients with acute recurrent seizures or periodic epileptiform activity. Methods: Using an EEG report database, we identified subjects who received LAC, PHT, or VPA while undergoing non-elective inpatient continuous EEG monitoring for recurrent seizures or periodic epileptiform patterns refractory to at least one AED between January 2007 and June 2010. Levetiracetam (LEV) was not included because of its frequency of use as a first line agent. Patient demographics, prior seizure history, underlying etiology, admission AEDs, AED changes, LAC titration schedule, adverse effects, and electrographic/clinical outcome were recorded. P-R intervals were measured on the single-lead EKG prior to and after starting LAC. Results: A total of 17 patients received LAC as add-on therapy for acute recurrent seizures or periodic epileptiform activity. LAC was the second or third agent in 15 patients and the fourth or fifth agent in 2 patients. In 12 patients, introduction of LAC resulted in improvement of seizures or periodic epileptiform activity (70.6%). Two patients required additional agents to control seizures. There were no complications directly attributable to LAC, and LAC was not discontinued in any patient during hospitalization because of side effects. Two patients tolerated an initial dose of 300 mg IV LAC followed by 200 mg bid, and three other patients were started on 200 mg bid, 2 of whom received the drug IV without reported complications. The average P-R interval did not significantly change after introduction of LAC (p=0.41). Eleven of 17 patients were discharged with LAC, including 6 patients directly home. In 5 patients, medical care was withdrawn. In comparison, 6 of 9 patients (66.7%) responded to PHT and 4 of 13 patients (30.8%) responded to VPA with EEG improvement. This suggests that the response rate to LAC is comparable to that of PHT and may be higher than that of VPA in our patient group. In addition, as a proxy measure of the effectiveness of LAC compared to LEV, 16 of 17 patients in our study were given LEV prior to LAC. Eleven of these patients had seizure improvement with initiation of LAC. Therefore, 64.7% of patients in our study were LEV-refractory and responsive to the addition of LAC. Conclusions: Our data suggest that LAC is safe, well-tolerated, and effective as an add-on treatment in critically ill patients with acute recurrent seizures or periodic epileptiform activity refractory to at least one other AED. Its efficacy is at least comparable to other AEDs traditionally used in these patients.