Background: Over the past three decades, NMDA-receptor antagonists have been shown to be efficient drugs for treating pain, particularly pain resistant to conventional analgesics. Emphasis will be on the old-new drugs, ketamine and magnesium, and their combination as a novel approach for treating chronic pain.
Methods: The MEDLINE database was searched via PubMed for articles that were published up to March 1, 2020, with the keywords ‘ketamine’, ‘magnesium’, and ‘pain’ (in the title/abstract).
Results: Studies in animals, as well as humans, have shown that interactions of ketamine and magnesium can be additive, antagonistic, and synergistic. These discrepancies might be due to differences in magnesium and ketamine dosage, administration times, and the chronological order of drug administration. Different kinds of pain can also be the source of divergent results.
Conclusion: This review explains why studies performed with a combination of ketamine and magnesium have given inconsistent results. Because of the lack of efficacy of drugs available for pain, ketamine and magnesium in combination provide a novel therapeutic approach that needs to be standardized with a suitable dosing regimen, including the chronological order of drug administration.