The off-label use of ketamine to deal with continual ache isn’t supported by scientific proof, a brand new Cochrane evaluate has discovered.
Ketamine is an anaesthetic generally used for procedural sedation and short-term ache reduction. Ketamine can also be steadily prescribed off-label to handle continual ache circumstances equivalent to nerve ache, fibromyalgia and sophisticated regional ache syndrome. It’s considered one of a number of NMDA receptor antagonists — a gaggle of medication thought to scale back ache by blocking sure mind receptors concerned in ache signalling.
The evaluate, carried out by researchers from UNSW Sydney, Neuroscience Analysis Australia (NeuRA), and Brunel College of London, examined 67 trials involving over 2,300 grownup individuals. It assessed 5 NMDA receptor antagonists: ketamine, memantine, dextromethorphan, amantadine, and magnesium. Outcomes present no clear proof of profit for ketamine in continual ache and recognized an elevated danger of antagonistic results equivalent to delusions, delirium, paranoia, nausea, and vomiting. Proof was rated low to very low certainty, as a result of small examine sizes and poor methodological high quality.
“We wish to be clear – we’re not saying ketamine is ineffective, however there’s lots of uncertainty,” stated Michael Ferraro, Doctoral Candidate at UNSW and NeuRA, first writer of the evaluate. “The info might level to a profit or no impact in any respect. Proper now, we simply do not know.”
Researchers regarded on the results throughout numerous continual ache circumstances and dosing methods however discovered no clear proof of profit in any particular situation or dose. Unintended effects have been a significant concern, significantly with intravenous use.
“The most typical antagonistic occasions we noticed have been psychotomimetic results equivalent to delusions, delirium and paranoia, in addition to nausea and vomiting.” stated Ferraro. “These results are distressing for a lot of sufferers. Clinicians typically attempt to steadiness the dose for ache reduction with out triggering these signs, however this is not at all times achieved.”
The evaluate additionally discovered no research that reported on two key outcomes: whether or not ketamine decreased depressive signs or opioid use. That is notable, as ketamine is commonly proposed for sufferers with depressive signs or opioid tolerance.
“This group of medication, and ketamine particularly, are in comparatively frequent use for continual ache world wide. But we have now no convincing proof that they’re delivering significant advantages for individuals with ache, even within the quick time period,” stated Neil O’Connell, Professor at Brunel College of London, co-senior writer of the evaluate. “That appears a very good cause to be cautious within the clinic and clearly signifies an pressing have to undertake top quality trials.”
The authors hope the evaluate will assist inform sufferers and clinicians weighing up potential advantages and harms, and information future analysis. Whereas extra proof is required, this evaluate highlights the significance of high-quality trials to know whether or not ketamine has a task in continual ache care.
“We have seen the hurt that may come from taking medicines developed for acute ache and making use of them to continual ache, opioids are a primary instance. Now we’re seeing the same sample with ketamine,” stated co-senior writer James McAuley, Professor at UNSW and senior researcher at NeuRA. “As opioid prescribing is slowly decreased, there is a rising demand for alternate options, however we have to be cautious to not rush into widespread use with out robust proof.”