Ketamine: A Powerful Anesthetic May Trigger Mental Health Side Effects

Unlike opioids, ketamine has no established effects on chronic pain, and no validated studies have confirmed this.

The off-label use of the strong anesthetic drug ketamine for long-term pain management has no proven scientific evidence to date, according to a new Cochrane study ().

Ketamine is a powerful anesthetic normally used in hospital procedures. Ketamine is also used for short-term pain management in hospitals. It works by blocking a brain signal receptor (NMDA receptor), that is involved in memory, mood, and pain perception. However, when ketamine doses are used for chronic pain conditions such as nerve pain, and fibromyalgia, it may result in adverse mental side effects as well as delusions, delirium, and hallucinations. It also can cause nausea and vomiting.

Ketamine: The Key to Postoperative Pain Relief?
Ketamine may be more effective in relieving postoperative pain in patients with a higher propensity for central sensitization, as indicated by TSP scores.

TOP INSIGHT

Did You Know?
Scientists advise caution on off-label use of #ketamine for #pain_relief. The drug can induce dangerous #psychosis-like symptoms such as delirium, and hallucinations. #chronicpain #mentalhealth #ketamine #medindia

Scientists from UNSW Sydney, Neuroscience Research Australia (NeuRA), and Brunel University of London, investigated on 67 trials over 2,300 adult participants. It assessed five NMDA receptor antagonists: ketamine, memantine, dextromethorphan, amantadine, and magnesium.

The findings showed no evidential support for ketamine in treating persistent pain conditions, and determined an elevated risk of mental side effects. Side effects were a major concern, particularly with intravenous use.

More Evidence is Needed for Ketamine in Chronic Pain Care

“We want to be clear – we're not saying ketamine is ineffective, but there’s a lot of uncertainty,” said Michael Ferraro, Doctoral Candidate at UNSW and NeuRA, first author of the review. “The data could point to a benefit or no effect at all. Right now, we just don’t know.”

The review also found no studies that reported on two key outcomes: whether ketamine reduced depressive symptoms or opioid use. This is notable, as ketamine is often proposed for patients with depressive symptoms or opioid tolerance.

"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,” said Neil O'Connell, Professor at Brunel University of London, 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.”

Opioids Without Side Effects For Pain Relief
Opioids relieve severe pain but also trigger a wide range of side effects from nausea, numbness, and constipation.

Weighing Ketamine’s Potential in Chronic Pain Management

The authors hope the review will help inform patients and clinicians weighing up potential benefits and harms, and guide future research. While more evidence is needed, this review highlights the importance of high-quality trials to understand whether ketamine has a role in chronic pain care.

“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,” said 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.”