NMDA Receptor Antagonists for the Treatment of Neuropathic Pain Compared to Placebo: A Systematic Review and Meta-analysis

The objective of this study is to evaluate the efficacy of N-Methyl-D-aspartate (NMDA) receptor antagonists on neuropathic pain disorders that can occur in the orofacial region. These disorders included: Postherpetic Neuralgia (PHN), Complex Regional Pain Syndrome (CRPS), Atypical Odontalgia, Temporomandibular Joint (TMJ) Arthralgia and facial neuropathies. Materials and Methods: Three databases (Medline through PubMed, Web of Science, and Cochrane library) were searched on January 25, 2017 for randomized placebo-controlled studies using a NMDA receptor antagonist to treat spontaneously occurring neuropathic pains as compared to placebo. Two review authors separately evaluated the risk of bias. Results: The initial search yielded 267 unduplicated references, of which only 16 were eligible for inclusion. Six of these studies had an unclear risk of bias and ten had a high risk of bias. Four studies were included for meta-analysis. Oral memantine was found not to be more effective than placebo in treating PHN (p=0.735), while oral and IV ketamine were more effective than placebo in treating CRPS (p<.001). Conclusions: The quality of the evidence favorable to the use of ketamine in the treatment of CRPS is low. Inconclusive evidence in favor of other NMDA antagonist receptors was found. Additional studies with lower risk of bias and larger sample sizes are needed in this area of study.