Thursday, April 16, 2009

Opioid antagonists for pain

Pain Treatment Topics has a review on the clinical use of opioid antagonists as analgesics/analgesic adjuncts (free full-text pdf here).

This is a topic I've been following with interest the last few years and this review is the most accessible summary on the work that has been coming out about it. In short, there have been some tantalizing case series and small trials (as well as a large amount of non-clinical human and animal research) suggesting that opioid antagonists (e.g. naloxone and naltrexone), at tiny doses (not enough to cause withdrawal/reverse analgesia) MAYBE are some combination of: analgesic by themselves or beneficial adjuncts to patients on regular opioid agonists (can attenuate some side effects, reduce tolerance, attenuate opioid agonist hyperalgesic effects, etc.). This is aside from the ongoing work to develop combination opioid antagonist-agonist products which are less-easily abused (extended release oxycodone which releases a hefty dose of naltrexone when crushed, etc.).

I had been aware of the theory and animal studies behind this for a while, but it wasn't until this case series in 2006 that I began wondering seriously if this was a line of inquiry which might lead to significant clinical benefit to our patients. I still am not sure of course; but this review seems to me a good argument for seriously investigating this in decent-sized human trials. I am not sure if this is being considered or not.

My own perspective on this is that, at least for cancer pain, the good news is that a large majority of patients (85-95% - this is my own clinical gestalt) can receive adequate analgesia with tolerable side effects, despite progressive cancer, with the relatively straight-forward, judicious use of the typical opioids and other analgesics we have available to us. That leaves however the 'unlucky 5%' (or whatever fraction) for whom all the usual moves (escalation, rotation, try different route, use down-the-line adjuvants, etc.) don't work: persistent intolerable side effects, hyperalgesia and/or persistent tolerance to the analgesic effects of opioids. It's this group of patients (whom I assume get concentrated in palliative care environments as they require specialist level help with pain management) for whom these interventions, if they actually work, might be particularly helpful. It might however make the research more difficult however: if most people do just fine, it makes it more difficult to demonstrate benefit, as well as there being multiple reasons individuals don't do 'just fine,' etc. etc.

So we'll see. Is anyone using opioid antagnoists clinically for these reasons? Please tell.

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