Dextromethorphan Versus Placebo for Neuropathic Pain

Summary

In our current clinical trial, we are comparing the effects of two NMDA receptor antagonists to placebo in patients with painful distal symmetrical diabetic neuropathy or post-herpetic neuralgia. The treatments in this three-period crossover study are dextromethorphan, up to 920 mg/day (about 8 times the antitussive dose), memantine, 30-50 mg/day, and placebo. Memantine is an NMDA antagonist used in Europe to treat Parkinson's disease and Alzheimer's disease. The underlying hypothesis, based on studies of painful neuropathies in animal models, is that neuropathic pain is caused largely by sensitization of central nervous system neurons caused by excitatory amino acid neurotransmitters, acting largely through NMDA receptors. A previous small trial of dextromethorphan suggested efficacy in diabetic neuropathy pain. The study requires one visit to the NIH outpatient Pain Research Clinic, and consists of three 9-week treatment periods. Patients who respond to one of the medications will be invited to participate in further controlled studies of the medication followed by up to several years of open-label treatment under continued observation.

Timeline

Start

1993-03

Primary completion

—

Completion

2001-02

Publications

• Background Albers GW, Saenz RE, Moses JA Jr, Choi DW. Safety and tolerance of oral dextromethorphan in patients at risk for brain ischemia. Stroke. 1991 Aug;22(8):1075-7. doi: 10.1161/01.str.22.8.1075.
• Background Bakshi R, Faden AI. Competitive and non-competitive NMDA antagonists limit dynorphin A-induced rat hindlimb paralysis. Brain Res. 1990 Jan 15;507(1):1-5. doi: 10.1016/0006-8993(90)90512-a.
• Background Choi DW. Dextrorphan and dextromethorphan attenuate glutamate neurotoxicity. Brain Res. 1987 Feb 17;403(2):333-6. doi: 10.1016/0006-8993(87)90070-9.

Drugs

Indications