Tolerability of lamotrigine in patients with painful diabetic neuropathy: Results from two large double-blind trials

Abstract

Lamotrigine is a voltage dependent Na channel blocker and also inhibits the pathological release of glutamate. The tolerability profile of lamotrigine is well established in patients with epilepsy and bipolar disorder. We report the tolerability of lamotrigine in patients with neuropathic pain. Two replicate multi-center, randomized, double-blind studies (NPP30004/NPP30005) were conducted to evaluate the tolerability and efficacy of lamotrigine in patients with painful diabetic neuropathy (PDN) and data were pooled for analysis. Patients with PDN and a baseline pain score of ≥4 on a 0–10 scale were randomized 1:1:1:1 to receive lamotrigine 200, 300, 400mg/day or placebo. The studies included a 7-week dose escalation phase and a 12-week fixed dose maintenance phase. Each study randomized 360 patients and 532 patients received lamotrigine for up to 19 weeks (NPP30004=267, NPP30005=265). The most common adverse events in patients receiving lamotrigine were headache (16%), dizziness (8%) and nausea (8%). The incidence of rash was similar across treatment groups (5% of placebo patients; 7% of lamotrigine patients). A single serious rash was reported. A patient receiving lamotrigine 25mg/day for 10 days was hospitalized for viral syndrome with rash and fever; the rash resolved without complications. The incidence of serious adverse events was also similar between the placebo (6%) and lamotrigine (7%) groups. 17% of lamotrigine-treated patients withdrew from the study due to an adverse event as compared to 12% of placebo patients. These studies suggest that lamotrigine 200–400mg/day is generally well tolerated in patients with painful diabetic neuropathy.