title: Open Label Trial of Add on Lacosamide Versus High Dose Levetiracetam Monotherapy in Patients With Breakthrough Seizures.
abstract: OBJECTIVE
  In patients who do not achieve seizure freedom on low-dose first-line monotherapy antiepileptic drug (AED), the current practice is to increase the AED to higher doses. For patients who fail low dose levetiracetam (LEV), a reasonable alternative to increasing dosage may be the addition of a low-dose adjunctive AED.
  
  
  METHODS
  In this open-label, pilot trial, low-dose lacosamide (200 mg/d) was added to adult patients with breakthrough seizures on low-dose monotherapy LEV (≤1500 mg/d). Comparison was made with a retrospective historical control cohort in whom the dose of LEV was raised after a breakthrough seizure. The main objectives were to determine efficacy effect size and tolerability.
  
  
  RESULTS
  Twenty patients were recruited in the prospective polytherapy cohort, of whom 19 received at least 1 dose of adjunctive AED; the monotherapy cohort consisted of 36 patients. Six-month seizure freedom was achieved in 9 of 19 patients in the polytherapy cohort and in 15 of 36 patients in the monotherapy cohort (hazard ratio for seizure occurrence for polytherapy relative to monotherapy was 0.76; 95% confidence interval, 0.35-1.65; P = 0.49). There were treatment emergent adverse effects in 11 patients (61.1%) in the polytherapy cohort and 26 (72.2%) in the monotherapy cohort. Greater number of patients in the monotherapy cohort experienced irritability/depression (33.3% vs 5.6%, P < 0.05).
  
  
  CONCLUSIONS
  Low-dose polytherapy with LEV and lacosamide was well tolerated and efficacious. Further studies are needed to determine whether this is a reasonable alternative to high-dose LEV monotherapy.
authors.affiliation: *Department of Neurology, The Edward B. Bromfield Epilepsy Program, Brigham and Women's Hospital, Harvard Medical School; and †Department of Biostatistics, Brigham and Women's Hospital, Boston, MA.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Lee
authors.forename: Javad
authors.initials: J
authors.lastname: Alam
authors.forename: Nichelle
authors.initials: N
authors.lastname: Llewellyn
authors.forename: Shelley
authors.initials: S
authors.lastname: Hurwitz
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Bubrick
authors.forename: Rani A
authors.initials: RA
authors.lastname: Sarkis
authors.forename: Daniel
authors.initials: D
authors.lastname: Weisholtz
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Swapna
authors.initials: S
authors.lastname: Putta
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Dworetzky
authors.forename: Page B
authors.initials: PB
authors.lastname: Pennell
mesh_terms: D000081:Acetamides / Q000627:therapeutic use*; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D000078334:Lacosamide; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D000077287:Levetiracetam; D000078334:Lacosamide; D010889:Piracetam