We all know what it's like to want something that's bad for us. I'm skipping the ton of pop (and country) song references and moving right past that Michael Douglas and Glenn Close movie in the interest of time to deliver the main point upfront: oxycodone (including Percocet, folks) is more addictive than any other prescription opioid out there. Yes, even worse than Dilaudid. Prescribe something else.
In November, the American Journal of Emergency Medicine published a nice prospective, randomized, comparing equipotent (per standard conversion tables) doses of morphine plus acetaminophen versus Percocet for acute pain in the ER. (It's 20 years of experience, not necessarily jadedness that leads me to say that the investigators' choice to exclude subjects with histories of opioid dependence or current opioid use was a wise one in terms of overturning the null hypothesis of significant difference in perceived analgesic efficacy between the two.)
If your research-geek credentials are up to date you'll have no trouble translating the primary outcome: both options get the job done – in terms of satisfactorily treating severe pain. (Interestingly, there was a non-significant trend toward greater efficacy in the morphine group.) Even more interesting, though (and consonant with 7 decades of anecdotal and published data) is the fact that Percocet recipients reported feeling twice as high as morphine recipients, and on a scale of 0-100, those receiving Percocet rated the drug's desirability at 49.3 on average compared with 29.9 for morphine.
Bear in mind, these were opioid-naïve individuals. I'll present even more striking data in just a moment from opioid-experienced individuals.
The thing is, oxycodone is just plain more likable, right off the bat. Some have argued over the years that it's due to a reduced side effect profile; those claims haven't been borne out in the literature, but anecdotally it does seem a little cleaner in terms of nausea and pruritus.
What we do know is that oxycodone races through to the brain something like 600% quicker than morphine does, and tenaciously stimulates a sustained mesolimbic dopaminergic response (addiction science parlance for "WOW – I want more of THAT!") that to our knowledge is unparalleled among prescription opioids.
That's not all, though; owing to some other unique pharmacologic properties we'll discuss in a minute, oxycodone rapidly becomes more than likable – it becomes a want and even a perceived need. (We can want something we no longer like, and we can like something we don't really want; scientists have demonstrated that the want factor is way more important than the likeability quotient in terms of the development of addiction.)
Our group looked at this a couple of years ago in a slightly different setting -- our pain clinic. We took a reverse approach, sampling patients who came to us already dependent on opioids and asked them what they -- and the drug-using community they knew -- felt was (1) the most desirable and (2) the most addictive. (We also asked the subset of heroin users which drug they felt was their gateway to heroin use.)
We got the idea for this study from our experience trying to help chronic pain patients overcome opioid dependence, after noticing over the years that oxycodone caused the most problems (hyperalgesia, addictive behaviors, psychosocial and legal problems) of any prescription opioid out there.
Well, the patients agreed: 60% said oxycodone was the most desirable in their experience, 75% said oxy was the most desirable among the drug-using community, and 60% said oxy was the most addictive. And 78% of our heroin users named oxy as their gateway drug.
We also reviewed the literature going back to 1950 and found that our experience wasn't unique.
But it's not just the likeability of oxycodone that's problematic; it also has a disproportionate hook in terms of withdrawal scourge, having to do with unparalleled kappa receptor agonism. In other words, it isn't just that the highs are higher, but also that the lows are lower.
In real-world terms, addiction always starts out as the pursuit of pleasure but at some point morphs into an all-consuming need to outrun the horrible symptoms of going without.
So what's a provider to do?
It's a poor analogy, but work with me here: your 5-year-old has been out shopping with you all day (pre-COVID-19 of course) and needs something to drink. You've got the choice to give little Johnny a glass of water (or maybe some orange juice) versus a soda pop. They'll both get the job done, but which is more likely to cause any number of problems in the short- and long-run?
You're in that ER situation we led off with now.
OK, let's change it up a little (put you in my pain clinic): Johnny's already developed a thing for the cola. You've both been out at the car dealership for the past 5 hours after you picked him up from daycare after work. It's 21:00 hours (because the salesperson needs to talk to the manager again) and little J has had more than he can take -- and he's thirsty.
But not just hypernatremic and preload-down; he's after that syrupy, effervescent nectar. After all, he's been throwing it down nearly every day for the past couple years, and if it weren't bad enough, negotiating Kelley Blue Book values with Bob at 9 p.m. after managing four unit patients and 23 more on the floor today, now you've got a much more volatile situation involving a maxed-out 55 lb combatant wielding a 150-decibel shriek and it's cola or the threat of a call from child protective services. (Translate this to 4:30 p.m. on a Friday afternoon in your clinic, and you know exactly what I'm talking about. Bad online review at best; threat of physical violence at worst.)
Again, so what's a provider to do?
We've taken the hardline stance that we don't prescribe oxycodone (including Percocet) outside the context of maybe a 7-day postoperative course. We don't (usually) just cut folks off altogether, though; there are different beverage choices if thirst is really the issue.
Let's just get one thing clear, though, right off the bat, if it's not a need for more fluid and simply a hooked-on-cola temper tantrum, there's really only one option. Talking about buprenorphine here; prescribing opioids other than buprenorphine for opioid addiction is illegal.
Let's say Johnny really is dehydrated/the patient really does have severe pain refractory to more conservative means, and oh, by the way, is oxycodone-dependent: there are other options. We often use morphine -- or better yet tapentadol -- as a bridge to buprenorphine and/or opioid discontinuation.
And for those special people who are allergic to everything except oxycodone? Thank heavens for oxymorphone -- oxycodone's chief active metabolite. The patient is full of it (oxymorphone, that is) and can't possibly be allergic. Doesn't cross the blood-brain barrier with the same degree of zest – not nearly as fun -- but gets the job done.
All right, in conclusion, a nod to the moral of that scary and not terribly far-fetched 1987 blockbuster: "I won't be ignored, Dan!" Would've been so much better if that first, let alone second, encounter never happened.
, is a board-certified anesthesiologist, pain physician, and addictionologist practicing in Alaska (the military sent him there and he decided to stay). If he wasn't trying to guide people in improving their own lives, teaching medical students to do the same, or writing about it, he'd probably be outdoors right now slogging up a mountain with a good friend or two.