Lacosamide as adjunctive therapy for partial-onset seizures: a randomized controlled trial.
OBJECTIVE
To evaluate the efficacy and safety of lacosamide (400 and 600 mg/day) as adjunctive treatment in patients with uncontrolled partial-onset seizures taking one to three concomitant antiepileptic drugs (AEDs).


METHODS
This multicenter, double-blind, placebo-controlled trial randomized patients 1:2:1 to placebo, lacosamide 400 mg, or lacosamide 600 mg/day. After an 8-week baseline period, patients began treatment with placebo or lacosamide 100 mg/day, were force-titrated weekly (100 mg/day increments) to the target dose, and entered a 12-week maintenance period.


RESULTS
A total of 405 patients were randomized and received trial medication. Most (82.1%) were taking two to three concomitant AEDs. Median percent reductions in seizure frequency per 28 days from baseline to maintenance (intention-to-treat, ITT) were 37.3% for lacosamide 400 mg/day (p = 0.008) and 37.8% for lacosamide 600 mg/day (p = 0.006) compared to 20.8% for placebo, with responder rates of 38.3% and 41.2%, respectively, compared to placebo (18.3%, p < 0.001; ITT). Patients randomized to lacosamide showed large reductions in secondarily generalized tonic-clonic seizures, with median percent reductions in seizure frequency of 59.4% for lacosamide 400 mg/day and 93.0% for lacosamide 600 mg/day compared to 14.3% for placebo, and responder rates of 56.0% and 70.2% compared to placebo (33.3%). Dose-related adverse events included dizziness, nausea, and vomiting.


CONCLUSIONS
Adjunctive treatment with lacosamide 400 and 600 mg/day reduced seizure frequency for patients with uncontrolled partial-onset seizures. Lacosamide 400 mg/day provided a good balance of efficacy and tolerability; lacosamide 600 mg/day may provide additional benefit for some patients as suggested by secondary efficacy analyses, including response in patients with secondarily generalized tonic-clonic seizures.
Chung
Steve
S
Barrow Neurological Institute, Phoenix, Arizona 85013, USA. steve.chung@chw.edu
Sperling
Michael R
MR
Biton
Victor
V
Krauss
Gregory
G
Hebert
David
D
Rudd
G David
GD
Doty
Pamela
P
D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D004244:Dizziness / Q000139:chemically induced; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D012640:Seizures / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D055815:Young Adult
D000081:Acetamides; D000078334:Lacosamide