Ketamine for Chronic Non-Cancer Pain: A 2023 Update

Key Message

What Is the Issue? Doctors use ketamine to induce loss of consciousness as general anesthesia during surgery. At low doses that do not produce dissociation, practitioners use ketamine to relieve acute or chronic pain. The previous CADTH report published in 2020 found that IV ketamine, compared to placebo, could only provide short-term pain relief in patients with chronic non-cancer pain, with increased risks of nausea, vomiting, and psychomimetic effects. The included guidelines did not provide definitive recommendations due to insufficient evidence. Decision-makers want to know if there is any new evidence to support the use of ketamine for treating of chronic non-cancer pain in adults.

What Did We Do? To inform decisions about the use of ketamine for treating of chronic non-cancer pain, CADTH sought to update the previous report by identifying and summarizing literature comparing the clinical effectiveness and cost-effectiveness of ketamine with placebo or other pharmacological therapies for chronic non-cancer pain. We also attempted to identify evidence-based recommendations from most recent guidelines for the use of ketamine for chronic non-cancer pain. A research information specialist conducted a literature search of the peer-reviewed and grey literature with a search strategy focused on ketamine, chronic non-cancer pain, and adults. The search was limited to English-language documents published since 2020 up to November 06, 2023. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.

What Did We Find? We found 3 SRs and 1 randomized controlled trial on the use of ketamine for the treatment of patients with neuropathic pain, complex regional pain syndrome, fibromyalgia, and other chronic pain conditions. Collective evidence from the included studies suggests that ketamine treatment was associated with short-term pain reduction in patients with chronic non-cancer pain. However, the long-term efficacy of ketamine in pain relief remains unclear. Adverse events (AEs) associated with ketamine treatment were with psychedelic effects, discomfort, dizziness, fatigue, headache, and nausea; all of those events appeared to be short-lasting. There were mixed results regarding the effect of ketamine on quality of life and functional improvement. We did not find any studies on the cost-effectiveness of ketamine or new evidence-based guidelines on the use of ketamine for treating chronic non-cancer pain.

What Does It Mean? The findings in this review are consistent with the previous CADTH report published in 2020. Well-controlled studies with larger populations and longer follow-ups are needed to determine the optimal treatment protocol of ketamine for each specific type of chronic pain. Given that ketamine is a dissociative drug that could be associated with the development of a substance use disorder, decision-makers may wish to consider the use of ketamine for long-term treatment of chronic non-cancer pain. The long-term effects and dangers of ketamine remain to be determined.