 Ketamine, a general anesthetic and an N-methylde aspartate receptor, or NMDA antagonist, is frequently used to manage chronic pain. Magnesium has also been proposed to potentially augment that pain relief, since it physiologically blocks the NMDA receptor. Unfortunately, few studies have rigorously investigated ketamine's ability to relieve pain for more than a few weeks, alone or in combination with magnesium. So do the drugs work? A new clinical trial, published in the journal Anesthesiology, suggests they may not. In a triple crossover double-blinded randomized controlled trial, researchers did not find a significant reduction in reported pain with ketamine alone or with added magnesium. For the study, researchers in France recruited 20 patients with refractory neuropathic pain who had never taken ketamine. The patients received in random order IV infusions of either ketamine, ketamine and magnesium, or a saline placebo, every 35 days. Participants then filled out pain diaries in which they rated their pain each day, as well as additional questionnaires on emotional health, sleep and quality of life after each five-week period. At 35 days there was no significant difference in pain intensity, as evaluated by the area under the curve between any of the treatment groups, nor were there significant differences in the secondary questionnaire results. There was also no indication that those receiving two consecutive ketamine treatment periods were any better off than those who were given placebo in between. A few patients did, however, improve with either ketamine or ketamine with magnesium at day 7 or day 35, although this was also the case for some with placebo. The results suggest that, at least as studied, ketamine is not effective for neuropathic pain and that magnesium does not offer any additional benefit. A larger study might be able to identify common features of ketamine responders.