Dextromethorphan for Painful Diabetic Neuropathy

Source: Nelson KA, et al. High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 1997;48:1212-1218.

Animal model and clinical evidence indicate that N-methyl-D-aspartate (NMDA) blockers may alleviate certain forms of neuropathic pain. Accordingly, Nelson et al studied dextromethorphan, a low-affinity NMDA channel blocker, for the treatment of neuropathic pain (Tal M, Bennett G. Neurosci Lett 1993; 151:107-110; Backonja M, et al. Pain 1994;56:51-57; Eide P, et al. Pain 1995;61:221-228). Two groups of patients—one with painful diabetic neuropathy (n = 14), the other with postherpetic neuralgia (n = 18)—were randomized into double-blind, six-week crossover trials of dextromethorphan or placebo. Thirteen patients in each group completed the trial, three dropping out due to sedation, one due to ataxia and confusion, and one each with chest pain and sixth nerve palsy. Dextromethorphan, at a mean dose of 381 mg/d, significantly reduced neuropathic pain in the diabetics by a mean of 24% compared to placebo (P = 0.01), but a mean dose of 439 mg/d was of no benefit in postherpetic neuralgia. Dizziness and lightheadedness were the most frequent side effects noted (n = 8) in those completing the trial, but problems with hyperglycemia or hypoglycemia were not noted. Dextromethorphan may hold promise for the treatment of painful diabetic neuropathy, but the results of larger and longer trials are necessary to recommend it so. —mr