Background and Objectives Mexiletine is an oral sodium channel antagonist that has been reported to be effective in a variety of neuropathic pain syndromes. However, recent reports question the efficacy of oral mexiletine in neuropathic pain. The objectives of this study were to examine the effect of oral mexiletine on pain, neurosensation, allodynia, and quality of life.

Methods Twenty subjects suffering from neuropathic pain with prominent allodynia were enrolled in a randomized placebo-controlled crossover study. Patients were titrated to a maximum dose of 900 mg/d or doselimiting side effects, whichever occurred first. At baseline and on days 0, 4, 7, and 10, the following tests were performed: (1) Quality of Life Questionnaires; (2) pain scores; (3) area of allodynia; (4) side effects; (5) neurosensory testing; and (6) peak and trough plasma mexiletine levels.

Results Peak plasma levels occurred on day 10 and were 0.54 μg/mL. There was no significant effect on any quality of life measurement. There was no significant effect on any neurosensory threshold or the area of allodynia. There was a significant effect of mexiletine on stroking-induced pain. There were no significant effects on any other pain score. Side effects were negligible.

Conclusions At doses of up to 900 mg/d, mexiletine has minimal effects on pain and allodynia of neuropathic pain. However, side effects may preclude higher doses.