Oral Ketamine as an Analgesic Therapy: Systematic Review of Randomised Clinical Trials

Ketamine is an analgesic used to manage neuropathic pain, but its use is limited by side effects and intravenous administration. Recently, the use of oral and nasal administration has expanded. However, no systematic review of randomized studies on its efficacy and safety. A search was conducted in PubMed, CINHAL, and Web of Science up to December 19, 2023. Randomized studies evaluating oral ketamine for managing any type of pain were included. Articles were assessed for quality using the ROB2 tool, and results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search yielded 1439 results. Six randomized studies were selected. The oral ketamine dose ranged from 0.5 to 10 mg/kg, up to a maximum of 400 mg/day. Three studies comparing oral ketamine with other analgesics found no differences between groups. Two studies compared oral ketamine to placebo; one showed a reduction in local anesthetic use and intraoperative pain, while the other found no difference. Adverse reactions were common, but their severity was not reported. Preliminary evidence suggests that oral ketamine may be considered in select patients with refractory chronic neuropathic pain. The potential use in outpatient settings warrants further high-quality studies.