Ketamine for Chronic Pain: evidence Fails to Support Off-Label Use
Sydney, Australia – A extensive review published August 17, 2025, challenges the widespread practice of using ketamine to manage chronic pain, finding no definitive evidence of benefit and highlighting potential adverse effects. The research, conducted by scientists at UNSW Sydney, neuroscience Research Australia (NeuRA), and Brunel University of London, raises critical questions about the off-label prescription of this anesthetic.
What is Ketamine and Why is it Used for Chronic Pain?
Ketamine, primarily used as an anesthetic for short-term pain relief and procedural sedation, has increasingly been prescribed “off-label” for conditions like nerve pain, fibromyalgia, and complex regional pain syndrome.This practice stems from ketamineS classification as an NMDA receptor antagonist – drugs believed to interrupt pain signals in the brain by blocking specific receptors. However, the new review casts significant doubt on this therapeutic approach.
Key Findings of the Cochrane Review
Researchers analyzed data from 67 clinical trials, encompassing over 2,300 adult participants, evaluating five NMDA receptor antagonists: ketamine, memantine, dextromethorphan, amantadine, and magnesium. The results, published in the Cochrane Database of Systematic Reviews, revealed a lack of clear evidence supporting ketamine’s effectiveness in alleviating chronic pain. Furthermore,the review identified an increased risk of troubling side effects,including delusions,delirium,paranoia,nausea,and vomiting.
“We want to be clear-we’re not saying ketamine is ineffective, but there’s a lot of uncertainty,” explained Michael Ferraro, Doctoral Candidate at UNSW and NeuRA, and lead author of the review. “The data could point to a benefit or no effect at all. Right now, we just don’t know.”
The analysis considered various chronic pain conditions and dosage strategies, yet failed to demonstrate a consistent benefit in any specific scenario. Intravenous administration appeared to carry a notably high risk of adverse reactions.
Did You know? Chronic pain affects an estimated 20% of adults worldwide, making it a significant public health concern. Finding effective and safe treatments remains a major challenge.
Adverse effects and Unanswered Questions
Researchers reported that psychotomimetic effects – delusions, delirium, and paranoia - were among the most frequently observed adverse events. Nausea and vomiting were also common. Clinicians frequently enough attempt to balance dosage to maximize pain relief while minimizing thes psychological symptoms, but achieving this balance proves difficult.
Notably, the review found no studies that assessed ketamine’s impact on depressive symptoms or opioid usage. This is a critical gap in knowledge, given that ketamine is sometimes proposed as a treatment for co-occurring depression or as a means to reduce reliance on opioid painkillers.
Summary of Review Findings
| Factor | Finding |
|---|---|
| Evidence of Benefit | No clear evidence for ketamine in chronic pain |
| adverse Effects | Increased risk of delusions, delirium, paranoia, nausea, vomiting |
| Study Quality | Low to very low certainty due to small sample sizes and methodological limitations |
| Impact on Depression | No studies reported on effects on depressive symptoms |
| Impact on Opioid Use | No studies reported on effects on opioid use |
Call for Further Research
“This group of drugs, and ketamine in particular, are in relatively common use for chronic pain around the world. Yet we have no convincing evidence that they are delivering meaningful benefits for people with pain, even in the short term,” stated Neil O’Connell, Professor at Brunel University of London, and co-senior author of the review. “That seems a good reason to be cautious in the clinic and clearly indicates an urgent need to undertake high-quality trials.”
Pro Tip: If you are considering ketamine treatment for chronic pain, discuss the potential risks and benefits thoroughly with your healthcare provider, and seek a second opinion.
The authors emphasize the importance of well-designed clinical trials to determine whether ketamine has a legitimate role in chronic pain management. They draw parallels to the opioid crisis, cautioning against the widespread adoption of treatments without robust scientific backing. “We’ve seen the harm that can come from taking medicines developed for acute pain and applying them to chronic pain. Opioids are a prime example. Now we’re seeing a similar pattern with ketamine,” explained co-senior author James McAuley, Professor at UNSW and senior researcher at NeuRA. “As opioid prescribing is slowly reduced, there’s a growing demand for alternatives, but we need to be careful not to rush into widespread use without strong evidence.”
What are your thoughts on the use of ketamine for chronic pain? Do you believe more research is needed before widespread adoption of this treatment?
More data: Ketamine and othre NMDA receptor antagonists for chronic pain,Cochrane Database of Systematic Reviews (2025). DOI: 10.1002/14651858.CD015373.pub2
Chronic Pain: A Growing Global Challenge
Chronic pain is a complex and debilitating condition affecting millions worldwide. Beyond the physical suffering, it can lead to depression, anxiety, and reduced quality of life. Current treatment approaches ofen involve a multidisciplinary approach, including medication, physical therapy, psychological support, and lifestyle modifications.The search for effective and safe pain management strategies remains a critical area of medical research.
Frequently Asked Questions About Ketamine and Chronic Pain
- What is ketamine? Ketamine is an anesthetic medication sometimes used off-label to treat chronic pain.
- Is ketamine effective for chronic pain? Current research, including a recent Cochrane review, does not support the use of ketamine for chronic pain due to a lack of conclusive evidence.
- What are the side effects of ketamine? Potential side effects include delusions, delirium, paranoia, nausea, and vomiting.
- Is ketamine a safe alternative to opioids? The review suggests caution, as ketamine carries its own risks and has not been proven to be a safe or effective alternative to opioids.
- What should I do if I’m considering ketamine treatment? Discuss the potential risks and benefits with your doctor and seek a second opinion.
Disclaimer: This article provides general information and should not be considered medical advice.Always consult with a qualified healthcare professional for any health concerns or before making any decisions related to your treatment.
We hope this article provides valuable insights into the current understanding of ketamine and chronic pain. Please share this information with anyone who may find it helpful, and feel free to leave your comments and questions below. Don’t forget to subscribe to our newsletter for the latest health news and updates!
