title: Lamotrigine for treatment of pain associated with diabetic neuropathy: results of two randomized, double-blind, placebo-controlled studies.
abstract: To assess the efficacy and tolerability of lamotrigine in pain associated with diabetic neuropathy, two replicate randomized, double-blind, placebo-controlled studies were conducted. Patients (n=360 per study) with painful diabetic neuropathy were randomized to receive lamotrigine 200, 300, or 400 mg daily or placebo during the 19-week treatment phase, including a 7-week dose-escalation phase and a 12-week, fixed-dose maintenance phase. The mean reduction in pain-intensity score from baseline to week 19 (primary endpoint) was greater (p < or = 0.05) in patients receiving lamotrigine 400 mg than placebo in Study 2 (observed scores, -2.7 versus -1.6 on a 0- to 10-point scale). This finding was not replicated in Study 1. Lamotrigine 200 and 300 mg did not significantly differ from placebo at week 19 in either study. Lamotrigine 300 and 400 mg were only occasionally more effective than placebo for secondary efficacy endpoints. The 200-mg dose did not separate from placebo. In a post hoc analysis of pooled data including only patients who reached their target dose, lamotrigine 400 mg conferred greater (p0.05) mean reduction in pain-intensity score from baseline to week 19 than placebo (-2.5 for 300 mg and -2.7 for 400mg versus -2.0 for placebo). Adverse events were reported in 71-82% of lamotrigine-treated patients compared with 63-70% of placebo-treated patients. The most common adverse events with lamotrigine were headache and rash. Compared with placebo, lamotrigine (300 and 400 mg daily) was inconsistently effective for pain associated with diabetic neuropathy but was generally safe and well tolerated.
authors.affiliation: Diabetes Institute, Eastern Virginia Medical School, 855 West Bramdleton, Norfolk, VA 23510, USA. vinikai@evms.edu <vinikai@evms.edu>
authors.forename: Aaron I
authors.initials: AI
authors.lastname: Vinik
authors.forename: Michael
authors.initials: M
authors.lastname: Tuchman
authors.forename: Beth
authors.initials: B
authors.lastname: Safirstein
authors.forename: Clinton
authors.initials: C
authors.lastname: Corder
authors.forename: Louis
authors.initials: L
authors.lastname: Kirby
authors.forename: Kerri
authors.initials: K
authors.lastname: Wilks
authors.forename: Steve
authors.initials: S
authors.lastname: Quessy
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Joanne
authors.initials: J
authors.lastname: Grainger
authors.forename: Jonathan
authors.initials: J
authors.lastname: White
authors.forename: Marianne
authors.initials: M
authors.lastname: Silver
mesh_terms: D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000453:epidemiology*; D010147:Pain Measurement / Q000187:drug effects*; D015990:Placebo Effect; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D016896:Treatment Outcome; D014227:Triazines / Q000627:therapeutic use*
chemical_list: D026941:Sodium Channel Blockers; D014227:Triazines; D000077213:Lamotrigine