There are several NMDA receptor antagonists available for different indications: ketamine, methadone, memantine, amantadine, and dextromethorphan. Amantadine is approved for treatment of Alzheimer’s disease and it has had mixed results for treating pain in clinical trials. A double-blind, randomized, placebo-controlled trial was conducted in 15 cancer patients who had surgical neuropathic pain. In a randomized order, patients received a 200-mg infusion of amantadine or placebo 1 week apart from each other. Spontaneous and evoked pain were measured 48 hours before, during, and after treatment. On average, there was an 85% pain reduction with amantadine versus 45% with placebo (P = .009) at the end of the infusion. When comparing mean pain intensity 48 hours prior to and following treatment, amantadine had a 31% reduction in pain (P = .006), whereas the placebo showed an insignificant pain reduction of 6% (P = .40).
In contrast to these positive results, Fukui et al conducted a study of amantadine in 19 patients who failed to respond to the conventional treatments for neuropathic pain, including anti-convulsants, antidepressants, and nerve blocks.24 The patients were started on oral amantadine 100 mg/day for 1 week and titrated to 200 mg/day. The results showed pain reduction in only 2 (10.5%) of the 19 patients. Adverse effects were experienced in 52.6% of the patients, including dry mouth, drowsiness, hallucinations, excitation, irritation, dizziness, dyskinesia, and loss of hair. There are no guidelines that currently support the use of amantadine as an adjuvant for chronic pain.
Pud D, Eisenberg E, Spitzer A, et al. The NMDA receptor antagonist amantadine reduces surgical neuropathic pain in cancer patients: a double blind, randomized, placebo controlled trial. Pain. 1998;75:349-354.
Fukui S, Komoda Y, Nosaka S. Clinical application of amantadine, an NMDA antagonist, for neuropathic pain. J Anesth. 2001;15:179-181.
Dana Jamero, PharmD, BCOP, The Emerging Role of NMDA Antagonists in Pain Management US Pharm. 2011;36(5):HS4-HS8
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