title: Minimizing pharmacodynamic interactions of high doses of lacosamide.
abstract: OBJECTIVE
  To determine whether pharmacodynamic interactions between high doses of lacosamide (400-800 mg/day) and concomitant sodium channel antiepilepsy drugs (AEDs) can be minimized in patients with drug-resistant partial-onset seizures.
  
  
  METHODS
  Patients were rapidly initiated with high-dose lacosamide (100 mg/week; increases to 400 to 800 mg/day), while simultaneously tapering concomitant sodium channel AEDs. Seizure frequency and side effects were evaluated at six time points: baseline, titration, 3, 6, 9 and 12 months.
  
  
  RESULTS
  Twenty-three patients had a baseline median of 4 seizures/month with persisting partial-onset seizures, despite previous treatment with an average of 6.8 AEDs. Mean decreases in monthly seizure frequency were as follows: 3 months 49.9% (P = 0.011), 6 months 55.4% (P = 0.010), 9 months 60.8% (P = 0.002) and 12 months 58.2% (P = 0.011). Most adverse events were mild CNS-related symptoms and occurred transiently only during titration - there was no significant relationship (χ(2) < 1.5, P > 0.1) between lacosamide dose and the presence of side effects at 3, 6, 9 or 12 months.
  
  
  CONCLUSIONS
  Drug-resistant patients rapidly titrated to high doses of lacosamide with simultaneous tapering of traditional sodium channel AEDs had marked reduction in CNS-related adverse events compared with patients treated in three previous pivotal trials that used fixed doses of concomitant AEDs.
authors: Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA. h.brooke.edwards@gmail.com
authors: H B
authors: HB
authors: Edwards
authors: A G
authors: AG
authors: Cole
authors: A S
authors: AS
authors: Griffiths
authors: B
authors: B
authors: Lin
authors: A
authors: A
authors: Bean
authors: G L
authors: GL
authors: Krauss
mesh_terms: D000081:Acetamides / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004828:Epilepsies, Partial / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000078334:Lacosamide; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012640:Seizures / Q000188:drug therapy*; D026941:Sodium Channel Blockers / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D000927:Anticonvulsants; D026941:Sodium Channel Blockers; D000078334:Lacosamide