Efficacy and safety of lacosamide in diabetic neuropathic pain: an 18-week double-blind placebo-controlled trial of fixed-dose regimens

Clin J Pain. 2009 Jun;25(5):376-85. doi: 10.1097/AJP.0b013e318196d2b6.


Objectives: The aims of this multicenter, randomized, placebo-controlled, double-blind trial were to confirm the efficacy of lacosamide at a daily dose of 400 mg/d and to explore the efficacy, safety, and tolerability of lacosamide 200 mg/d and 600 mg/d in the treatment of painful diabetic neuropathy.

Methods: The trial consisted of a 2-week run-in period, a 6-week titration phase, and a 12-week maintenance phase, during which patients received placebo or fixed doses of lacosamide 200, 400, or 600 mg/d. No back titration was allowed during the trial. The primary efficacy criterion was the change in Likert pain score from baseline to the average over the last 4 weeks of the maintenance phase in the intent-to-treat population.

Results: The lacosamide 400 mg/d group demonstrated statistically significant improvement in Likert pain score over placebo for the primary efficacy measure. At the end of treatment, 58% of patients in the lacosamide 400 mg/d treatment group achieved at least a 2-point or 30% reduction in Likert pain score, compared with 46% of placebo-treated patients. The lacosamide 200 mg/d group separated from placebo, but failed to show statistical significance for any of the primary or secondary outcome measures. The lacosamide 600 mg/d group was significantly more efficacious than placebo in the observed cases but not in the intent-to-treat population. This was probably secondary to a relatively high-premature withdrawal rate due to adverse events that occurred during the titration phase in that group. Overall lacosamide at daily doses of 200 to 400 mg was well tolerated, with 8% of patients discontinuing due to an adverse event from the 200 mg/d group and 23% from the 400 mg/d group compared with 9% in the placebo group. Discontinuations due to adverse events were highest in the 600 mg/d group (40%). The most common adverse events consisted of dizziness, nausea, tremor, headache, and fatigue. Somnolence, cognitive and behavioral side effects, weight change, and edema were notably low.

Discussion: Safety and efficacy analyses indicated that lacosamide 400 mg/d provided an optimal balance between efficacy and side effects in patients with painful diabetic neuropathy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / administration & dosage*
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics / administration & dosage
  • Comorbidity
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / epidemiology*
  • Dopamine Uptake Inhibitors / administration & dosage
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Female
  • Fibromyalgia / diagnosis
  • Fibromyalgia / drug therapy*
  • Fibromyalgia / epidemiology*
  • Humans
  • Incidence
  • Lacosamide
  • Male
  • Middle Aged
  • Pain Measurement / drug effects
  • Placebo Effect
  • Treatment Outcome
  • United States / epidemiology


  • Acetamides
  • Analgesics
  • Dopamine Uptake Inhibitors
  • Lacosamide