COMMENTARY

The Myth of Morphine Equivalent Daily Dosage

Michael E. Schatman, PhD; Jeffrey Fudin, PharmD

Disclosures

May 24, 2016

Introduction

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.

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