Ketamine for Chronic Non-Cancer Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines

Key Message

​This review included two systematic reviews and two randomized controlled trials regarding the clinical effectiveness of ketamine for treating of patients with chronic non-cancer pain, and two guidelines regarding the use of ketamine for this population. No studies regarding the cost-effectiveness of ketamine were identified.

Based on findings of one systematic review compared to placebo, intravenous ketamine infusions significantly reduced pain scores, and had significantly higher positive response rates within two weeks of follow-up, but with significantly higher incidence of nausea, vomiting and psychomimetic effects, including delusion, hallucination and dysphoria. The positive short-term effect of ketamine was independent to dose, types of chronic pain or adjunct medication.

Another systematic review found that topical ketamine and oral ketamine were not efficacious for treatment of neuropathic pain, while IV ketamine was more effective in pain improvement for various conditions of chronic neuropathic pain when compared to placebo.

One included randomized controlled trial found that intravenous ketamine significantly reduced pain compared to placebo in chronic pain patients who experienced acute exacerbation within 60 minutes of treatment, but the ketamine analgesic effect was not observed at 24 to 48 hours of follow-up. Incidence of adverse events was significantly higher in the ketamine group than that in the placebo group.

Another included randomized controlled trial found that intraoperative ketamine infusion significantly reduced immediate postoperative intravenous morphine consumption after spinal fusion surgery in chronic pain patients compared to placebo, with no significant differences between treatment groups regarding acute pain (two to 24 hours postoperative), persistent pain (six months postoperative), and adverse events.

One included guideline does not recommend intravenous ketamine infusion for various chronic pain conditions such as chronic persistent pain, complex regional pain syndrome, fibromyalgia and neuropathic pain due to insufficient evidence. The other guideline also did not find any strong evidence for intravenous ketamine infusion for immediate pain improvement in those pain conditions. 

Evidence in this review suggests that intravenous ketamine could only provide short-term pain relief in patients with chronic non-cancer pain, with increased risks of some adverse events such as nausea, vomiting and psychotomimetic effects.