NMDA Receptor Antagonists for the Treatment of Neuropathic Pain

Abstract

Objective. The N-methyl-D-Aspartate (NMDA) receptor has been proposed as a primary target for the treatment of neuropathic pain. The aim of the present study was to perform a meta-analysis evaluating the effects of (individual) NMDA receptor antagonists on neuropathic pain, and the response (sensitivity) of individual neuropathic pain disorders to NMDA receptor antagonist therapy. Design. PubMed (including MEDLINE), EMBASE and CENTRAL were searched up to October 26, 2009 for randomized placebo controlled trials (RCTs) on neuropathic pain. The methodological quality of the included trials was independently assessed by two authors using the Delphi list. Fixed or random effects model were used to calculate the summary effect size using Hedges' g. Setting. NA. Patients. The patients used for the study were neuropathic pain patients. Interventions. The interventions used were NMDA receptor antagonists. Outcome measurements. The outcome of measurements was the reduction of spontaneous pain. Results. Twenty-eight studies were included, meeting the inclusion criteria. Summary effect sizes were calculated for subgroups of studies evaluating ketamine IV in complex regional pain syndrome (CRPS), oral memantine in postherptic neuralgia and, respectively, ketamine IV, and oral memantine in postamputation pain. Treatment with ketamine significantly reduced pain in postamputation pain (pooled summary effect size: -1.18 [confidence interval (CI) 95% -1.98, -0.37], P=0.004). No significant effect on pain reduction could be established for ketamine IV in CRPS (-0.65 [CI 95% -1.47, 0.16], P=0.11) oral memantine in postherptic neuralgia (0.03 [CI 95% -0.51, 0.56], P=0.92) and for oral memantine in postamputation pain (0.38 [Cl 95% -0.21,0.98], P=0.21). Conclusions. Based on this systematic review, no conclusions can yet be made about the efficacy of NMDA receptor antagonists on neuropathic pain. Additional RCTs in homogenous groups of pain patients are needed to explore the therapeutic potential of NMDA receptor antagonists in neuropathic pain.