The Myth of Morphine Equivalent Daily Dosage

https://www.medscape.com/viewarticle/863477

For far too many years, pain researchers and clinicians have relied on the concept of the morphine equivalent daily dosage (MEDD), or some variant of it, as a means of comparing the “relative corresponding quantity” of the numerous opioid molecules that are important tools in the treatment of chronic pain. This concept dates back to the mid-1980s, first appearing in the cancer pain treatment guidelines by Portenoy and colleagues,^[1] and has subsequently been used empirically and clinically for a variety of purposes.

For example, researchers have relied on non-empirically derived “equivalent dosages” as a means to facilitate research in which opioid consumption serves as a dependent variable. Clinically, opioid “conversion” tables have been routinely used when switching a patient from one opioid to another. And, most unfortunately, opioid prescribing guideline committees have relied on this concept as a means of placing (usually arbitrary) limits on the levels of opioids that a physician or other clinician should be allowed to prescribe. Although these guidelines typically bill themselves as “voluntary,” their chilling effect on prescribers and adaptation into state laws^[2] makes calling them “voluntary” disingenuous.

Although some scientists and clinicians have been questioning the conceptual validity of MEDD for several years, a recent study^[3] has indicated that the concept is unequivocally flawed—thereby invalidating its use empirically and as a tool in prescribing guideline development. This analysis determined that a fundamental inadequacy of the MEDD concept is the lack of a universally accepted opioid-conversion method. The authors used survey data from pharmacists, physicians, nurse practitioners, and physician assistants to estimate daily morphine equivalents and found great inconsistency in their conversions of hydrocodone, fentanyl transdermal patches, methadone, oxycodone, and hydromorphone—illustrating the potential for dramatic underdosing or, in other cases, fatal overdosing.

Regarding the use of MEDD in research, our suspicion is that many pain investigators have known about the problems with this prodigiously flawed concept for many years. For example, in a 1991 Australian review of the polymorphic metabolism of opioids,^[4] the authors concluded that “Pharmacogenetics may play an important role in explaining the wide variability of the clinical response to many opioid drugs.” Yet, a quarter of a century later, MEDD remains routinely used in pain research worldwide. Given that invalid dependent variables in research result in invalid findings, our hope is that investigators will begin to conduct studies comparing morphine with morphine, hydrocodone with hydrocodone, and so on—as opposed to relying on the standard (and far more convenient) approach of MEDD.

Implications in the Clinic

Clinically, prescribers need to use this information regarding the flawed MEDD concept to begin practicing dosage-switching and opioid rotation in a more thoughtful and scientific manner. Thus, even if the charts suggest that 1 mg of oxycodone is the “equivalent” of 1.5 mg of morphine, the practice of opioid rotation based on the concept of pharmacogentic homogeneity needs to be seriously reconsidered.

Furthermore, the evidence supporting pharmacogenomic differences among patients is mounting^[5,6] and needs to be carefully weighed before labeling a patient who requires 30 mg of morphine rather than the prescriber’s “standard” of 10 mg in order to achieve adequate analgesia as an “addict.” Patients with chronic pain (particularly that of noncancer origin) who are reliant on opioid analgesia are already sufficiently stigmatized and marginalized^[7] to allow this type of practice to continue to be the norm.

Although the use of MEDD in research and, to a greater extent, in practice, is probably due to unawareness of its inaccuracy, we posit that the use of MEDD by recent opioid guideline committees (eg, the Washington State Opioid Guideline Committee^[8] and the Centers for Disease Control and Prevention Guideline Committee^[9]) in the drafting of their guidelines is based more heavily on disregarding available evidence rather than ignorance. Furthermore, their misconduct in doing so has been more pernicious than the use of MEDD by researchers and individual clinicians, because these guidelines widely affect society as a whole as well as individual patients with persistent pain syndromes. We opine that these committees are strongly dominated by the antiopioid community, whose agenda is to essentially restrict opioid access—irrespective of the lack of data indicating that opioids cannot be a useful tool in the comprehensive treatment of carefully selected and closely monitored patients with chronic pain.

Although we emphatically agree that opioid analgesia should not be the first-line treatment for chronic noncancer pain, when other nonopioid treatments have either failed, are contraindicated medically or owing to behavioral and emotional factors, or are inaccessible because of the health insurance industry’s refusal to cover them (irrespective of their established evidence-bases), opioids should be considered. Guidelines that contain language suggesting that alternative treatments are regularly available when this is not the case are shortsighted and troubling.

Recently, we published an article in the Journal of Pain Research titled “The MEDD Myth: The Impact of Pseudoscience on Pain Research and Prescribing-Guideline Development,”^[10] with Dr Jacqueline Pratt Cleary as our coauthor. This article goes into considerably more detail regarding the clinical and ethical imbroglio that we address in the current brief article, and as an open-access publication, the Journal of Pain Research encourages readers to access the full text at no cost here. We feel that the healthcare community must learn more about the need to work toward a paradigmatic revision in the consideration of opioids in research, clinical practice, and prescribing guideline development.

 

Filed under: General Problems