A Systematic Review of NMDA Receptor Antagonists for Treatment of Neuropathic Pain in Clinical Practice

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Abstract

Objective

To investigate the efficacy of N-methyl-D-aspartate receptor (NMDA) receptor antagonists for neuropathic pain and review literature to determine if specific pharmacologic agents provide adequate neuropathic pain relief.

Methods

Literature was reviewed on PubMed using a variety of key words for 8 NMDA receptor antagonists. These key words include: “Ketamine and Neuropathy”, “Ketamine and Neuropathic Pain”, “Methadone and Neuropathy”, “Methadone and Neuropathic Pain”, “Memantine and Neuropathic pain”, “Memantine and Neuropathy”, “Amantadine and Neuropathic Pain”, “Amantadine and Neuropathy”, “Dextromethorphan and Neuropathic Pain”, “Dextromethorphan and Neuropathy”, “Carbamazepine and Neuropathic Pain”, “Carbamazepine and Neuropathy”, “Valproic Acid and Neuropathy”, “Valproic Acid and Neuropathic Pain”, “Phenytoin and Neuropathy” and “Phenytoin and Neuropathic Pain”. With the results, the papers were reviewed using the PRISMA (Preferred Reporting in Systematic and Meta-Analyses) guideline.

Results

A total of 58 randomized controlled trials were reviewed among 8 pharmacologic agents, which are organized by date and alphabetical order. Of the trials for ketamine, 15 showed some benefit for analgesia. Methadone had 3 beneficiary trials, while amantadine and memantine each only had 2 trials showing neuropathic analgesic properties. Dextromethorphan and Valproic Acid both had 4 randomized controlled trials that showed some neuropathic treatment benefit while carbamazepine had over 8 trials showing efficacy. Finally, phenytoin only had 1 trial that showed clinical response in treatment.

Conclusion

It is evident there are a variety of NMDA receptor antagonist agents that should be considered for treatment of neuropathic pain. Nevertheless, continued and further investigation of the 8 pharmacologic agents is needed to continue to evaluate their efficacy for treatment of neuropathic pain.

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