Meaningless Milligrams: A Decade Later

I’m sure that many of our readers are familiar with several of the lifetime contributions from who I call “the academic pain psychology bros”, Drs. Ken Kirsh and Steven Passik.  While Ken continues to struggle with his long battle of colon cancer, many of us continue to ponder his writings daily. I remain captivated how a relatively obscure paper from 10 years ago was as sensible and on target then, as if the commentary was written yesterday.

Just last week I was reviewing the 2017 voting results for the baseball Hall of Fame and couldn’t help but think of Dr. Ken Kirsh and the wonderful tribute that Steve wrote for him here a year and a half ago, There IS Crying in Baseball.

Even in baseball we’ve learned “to look deeper, beyond the numbers, for meaning” as aptly outlined last week by NY Times writer Doug Glanville in For Baseball’s Hall of Fame, Do Statistics Alone Still Matter.

I am delighted to introduce our latest Student Pharmacist, Amelia Persico who is here today to discuss the seemingly timeless debated topic of opioids and “meaningless milligrams” after being assigned to read the 2007 commentary noted above. She did a wonderful job, and here’s what she had to say…

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It was 2007 when Drs. Kirsh and Passik eloquently asked in a commentary, “Will the Number of Milligrams of an Opioid Dose Ever Re-Achieve the Truly Meaningless Status It Deserves? [Hyperlinked with permission, Ref 2 below]  In their eponymous article, they suggest that ceiling opioid doses are more of a security blanket for providers than a therapeutic reality. In an industry where new research abounds daily and staying up-to-date requires constant vigilance in research and reading, it is shocking that a question asked ten years earlier remains not only relevant but profound to this day. The fear and stigma surrounding opioids has only increased over the last 10 years since their original article’s publication as the “opioid epidemic” and corresponding panic have swept the nation

The pervasive hesitance to escalate opioid doses comes from equal parts provider fear and misinformation. So what comfort can we offer these apprehensive prescribers, pens trembling over prescription pads (or, more aptly, fingers hovering over keyboard keys…)? And what solace can our patients in pain hope for?

Enter Mr. Smith and Mr. Jones. Two, fictitious, young gentlemen created by Drs. Kirsh and Passik to illustrate two disparate examples of the patient types who may request an opioid dose increase.  Both men are 28 years old, both are prescribed 160mg of sustained release oxycodone twice daily for their pain. Both men rate their pain at an 8/10 today which is a decrease from 10/10, on the same pain scale, at their last exam. They both report experiencing some opioid induced constipation (OIC) but are well controlled on a bowel regimen and report no other adverse effects of their medications. Objectively, these two men are quite similar.

Their differences begin with Mr. Jones’ positive marijuana toxicology screens (which he reports using for nausea and enhancing the effects of oxycodone), his history of early refills on oxycodone, and his statement that he “can do nothing until his pain levels come down.” They further diverge in Mr. Smith’s report that he has re-engaged in church services, resumed helping his wife with household chores and started pursuing his GED. Mr. Smith “passes” the 4-A filter.

The 4-A’s, as described by Kirsh and Passik, are analgesia, activity, adverse effects and aberrant drug taking behavior. They use the 4-As to justify titration to efficacy and tolerability as opposed to titration to some arbitrary mg number. I’ll repeat that last bit- titration to efficacy and tolerability as opposed to titration to some arbitrary mg number. In a class of drugs with no end organ damage and no real ceiling doses what better reasons to adjust doses than to titrate to efficacy and tolerability? If a patient is achieving adequate analgesia, pursuing activity as tolerated, not experiencing adverse effects and not exhibiting aberrant drug behavior then the reasons to refuse a dose increase are a bit foggy. Each patient responds to opioids differently. Prescribing and adjusting opioid doses using “cook book medicine” may comfort the prescriber but provides a disservice to the patient.

One method of grappling with opioid doses that has been offered throughout the literature is the concept of morphine equivalent dosing.  Fudin, Schatman and Cleary explored the relatively arbitrary designation of morphine equivalent daily doses (MEDD) for justifying the switch from one opioid to another “equivalent” dose.  Without even delving fully into this topic (Dr. Fudin already did, here) one can clearly see shortcomings of this methodology. First, despite a common mechanism of action, mu-opioid agonism, each opioid is metabolized in a different way. Further, each person may express different amounts of the mu-receptor. In this most simple example, a patient with 10 opioid receptors will react to a smaller amount of drug than a patient with 5.  In addition, variance among CYP enzyme expression via various genetic polymorphisms greatly effects patient response to opioids. Switching between opioids using MEDD, once again, serves mostly as a security blanket to providers.

So, back to our fictitious patients. Mr. Smith represents the ideal candidate for an opioid dose increase. He is experiencing inadequate analgesia at the current dose, is making every effort to return to his activities of daily living, is not abusing his medication or engaging in any aberrant behavior and is not experiencing any untoward side effects. Still, many providers would see the total daily dose of 320mg oxycodone and shudder to think of increasing further. There is, of course, a gray area to be explored in depth and I think that this is exactly what Kirsh and Passik ask us to do. They challenge us to see this “ideal patient” and to then look further to apply our knowledge, intuition and training to treat those who do not fit that mold.

There are plenty of reasons that an opioid dose increase may be warranted. Among them are tolerance and inadequate analgesia. But Kirsh and Passik challenge us to think beyond these reasons and enter the realm of metacognition in which we ask ourselves the reasons not to increase a dose. Their commentary suggests that each patient receive the comprehensive evaluation to which they are entitled without bias, preconceived notions or fear of a number. If we can let go of the stigma attached to a large milligram strength we may find ourselves free to treat patients more fully and without reservation. Because, as they so perfectly concluded, “We are treating patients, not massaging numbers.”

As always, comments are welcomed with enthusiasm!

 

BIO:  Amelia Persico is a 2017 Doctor of Pharmacy candidate at Albany College of Pharmacy and Health Sciences. In 2016, while attending pharmacy school, Amelia also received her MBA with a focus on health care management at Union Graduate College in Schenectady, NY. Amelia’s professional interests include geriatrics, community pharmacy and health care operations management, though she has yet to encounter a discipline within pharmacy that she does not enjoy. After graduation Amelia plans to pursue a career in community pharmacy and to never stop learning.

 

 

 

References:

1. Fudin, J, Cleary JP, Schatman, ME. The MEDD myth: The Impact of pseudoscience on pain research and prescribing-guideline development. Journal of Pain Research 2016:9 153-156.
2. Passik SD, Kirsh KL. Will the number of milligrams of an opioid dose ever re-achieve the truly meaningless status it deserves?. Journal of Pain & Palliative Care Pharmacotherapy. 2007 Jan 1;21(1):39-41