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Ketamine and Magnesium for Refractory Neuropathic Pain

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Authors: Gisèle Pickering, M.D., Ph.D., D.Pharm. et al
Anesthesiology 7 2020, Vol.133, 154-164.
Background: Ketamine is often used for the management of refractory chronic pain. There is, however, a paucity of trials exploring its analgesic effect several weeks after intravenous administration or in association with magnesium. The authors hypothesized that ketamine in neuropathic pain may provide pain relief and cognitive–emotional benefit versus placebo and that a combination with magnesium may have an additive effect for 5 weeks.Methods: A randomized, double-blind, crossover, placebo-controlled study (NCT02467517) included 20 patients with neuropathic pain. Each ketamine-naïve patient received one infusion every 35 days in a random order: ketamine (0.5 mg/kg)/placebo or ketamine (0.5 mg/kg)/magnesium sulfate (3g) or placebo/placebo. The primary endpoint was the area under the curve of daily pain intensity for a period of 35 days after infusion. Secondary endpoints included pain (at 7, 15, 21 and 28 days) and health-related, emotional, sleep, and quality of life questionnaires.Results: Daily pain intensity was not significantly different between the three groups (n = 20) over 35 days (mean area under the curve = 185 ± 100, 196 ± 92, and 187 ± 90 pain score-days for ketamine, ketamine/magnesium, and placebo, respectively, P = 0.296). The effect size of the main endpoint was −0.2 (95% CI [−0.6 to 0.3]; P = 0.425) for ketamine versus placebo, 0.2 (95% CI [−0.3 to 0.6]; P = 0.445) for placebo versus ketamine/magnesium and -0.4 (95% CI [−0.8 to 0.1]; P = 0.119) for ketamine versus ketamine/magnesium. There were no significant differences in emotional, sleep, and quality of life measures. During placebo, ketamine, and ketamine/magnesium infusions, 10%, 20%, and 35% of patients respectively reported at least one adverse event.Conclusions: The results of this trial in neuropathic pain refuted the hypothesis that ketamine provided pain relief at 5 weeks and cognitive–emotional benefit versus placebo and that a combination with magnesium had any additional analgesic effect.

Editor’s Perspective:

What We Already Know about This Topic:

  • The use of low-dose ketamine infusion for the treatment of chronic pain has expanded rapidly despite a paucity of data supporting the practice

  • Magnesium ion, like ketamine, is a blocker of N-methyl-d-aspartate receptor function that may have analgesic properties in some settings

What This Article Tells Us That Is New:

  • Using a triple-crossover paradigm, saline, ketamine, and ketamine + magnesium infusions were given to a group of 20 patients with chronic neuropathic pain

  • No effect of either the ketamine or ketamine + magnesium in terms of pain relief over the 35 days after infusions was identified

  • Additional secondary health-related, emotional, sleep, and quality of life measures were also unchanged by the drug infusionsReferences

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