Ketamine Infusions for Chronic Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

BACKGROUND: IV ketamine is widely used to treat patients with chronic pain, yet the long-term impact remains uncertain. We synthesized evidence from randomized control trials to investigate the effectiveness of IV ketamine infusions for pain relief in chronic conditions and to determine whether any pain classifications or treatment regimens are associated with greater benefit. METHODS: We searched Medline, Embase, and Google Scholar, as well as the clinicaltrials.gov website from inception through December 16, 2017 for randomized control trials comparing IV ketamine to placebo infusions for chronic pain that reported outcomes for ≥48 hours after the intervention. Three authors independently screened the studies, pooled the data, and appraised risk of bias. Random-effects model was used to calculate weighted mean differences for pain scores and secondary outcomes. Our primary outcome was the lowest recorded pain score ≥48 hours after cessation of treatment. Secondary outcomes included responder rate and adverse effects. RESULTS: Among 696 studies assessed for eligibility, 7 met inclusion criteria. All studies except one were at high risk of bias. These studies randomly assigned 211 patients with neuropathic (n = 2), mixed (n = 2), and nonneuropathic (nociplastic or nociceptive) (n = 3) pain. Three studies reported significant analgesic benefit favoring ketamine, with the meta-analysis revealing a small effect up to 2 weeks after the infusion (mean difference in pain scores, -1.83 points on a 0-10 numerical rating scale; 95% CI, -2.35 to -1.31 points; P