Sunday, January 22, 2006

Opioid switching for morphine unresponsive pain

I wanted to highlight an article from this month's Supportive Care in Cancer which looks at opioid switching for those not responding to morphine.  The study prospectively followed ~200 people started on morphine for cancer pain.  If patients were having 'intolerable' side effects or weren't responding to morphine despite usual titration they were switched to oxycodone.  Criteria to switch were not clearly or objectively defined--essentially relying on clinicians' judgments about what were intolerable side effects or 'unresponsiveness.'  (This is good in that it captures a real life situation well, but limits the ability to repeat this study or interpret what was done if one doesn't know how the decision to switch was actually made.)  About 1/4 of the patients underwent a switch. 

The good news is that the vast majority--90%--of patients who were switched had a good analgesia/side effect outcome after switching to oxycodone (a few ended up on methadone or fentanyl).  This is validation of the long standing and widely accepted practice of opioid switching.  I appreciate research like this:  looking, in a prospective and relatively controlled way, at the natural history of something everyone does to see if it actually helps & makes sense.  It's welcome news that it does help, and it would have been unsettling and actionable news if it didn't. 

The bad news is that I'm not sure if we learned anything else from this study, and it raised more questions than it answered.  Not surprisingly people who were switched had higher average pain levels, worse worst pain levels, and more severe side effects than those who weren't switched.  However, people who switched had lower average morphine doses and lower serum levels of morphine -3- and -6- glucuronide than those who didn't switch.  It doesn't make much of a difference, but one wonders if some of the people who were switched were just being underdosed on morphine.  Conversely, one could ask if there were genetic/pharmacologic reasons (cytochrome P450 polymorphisms, drug interactions) that lead the switchers to have lower M3G and M6G levels leading to worse analgesia.  The authors didn't divide out those who switched for pain control vs. intolerable side effects so it's impossible to know.  Oh well.  The authors also looked at patient characteristics to see if anything predicted who would be a switcher.  The results are curious, to say the least.  They found the following baseline characteristics predictive of who would switch:  higher weight; use of beta-blockers, proton pump inhibitors, and antiseritonergic antiemetics; higher wbc count; recent chemotherapy; and having a lower GI malignancy.  My gloss on this is that those with a higher symptom burden at baseline were more likely to 'fail' morphine due to side effects, but who knows. 

(The issue also publishes the results of a non-placebo controlled preliminary trial indicating that prophylactic fluconazole may dramatically reduce the rate of radiation mucositis.)

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