What an MME conversion actually is

A morphine milligram equivalent figure converts a dose of one opioid into a notionally equivalent dose of oral morphine using a fixed ratio, so that different drugs can be summed. The conversion factors come largely from single-dose studies in populations that are not the population being converted, and they do not account for what happens over weeks of therapy in a particular person.

For counting how much opioid is being dispensed in a state, this is a reasonable instrument. For deciding whether a specific patient is on too much, it assumes something the arithmetic does not contain: that people respond to a given quantity in roughly the same way.

How far apart people actually are

An analytic review of the clinical evidence on opioids in chronic pain examined dose requirements across enriched-enrollment randomized-withdrawal trials and found data suggesting roughly 13-fold variability in the dose required, with about 15-fold variability reported in post-surgical settings. The review attributes that spread to several separable sources:

• Severity of the underlying pain — the largest and most obvious factor, and the one an MME number contains no information about.
• Genetic differences in hepatic metabolism, which that review notes can account for three-fold or greater variability on their own.
• Genetic differences in receptor interaction, which differ between opioids, so two drugs that are “equivalent” on a conversion table are not equivalent in a given person.
• Differences in neural transmission.

Add bioavailability and elimination differences, and the proposition that a single threshold marks the boundary between safe and unsafe for everyone becomes hard to defend. The pharmacology is covered in more depth, including what is not established, on the pharmacogenomics page.

Why a threshold behaves differently from a caution

The 2016 guideline framed 50 and 90 MME/day as points at which a clinician should reassess and take additional precautions. Read as written, that is a prompt to think. Read as a number in a statute, a payer edit or a pharmacy system, it becomes a ceiling — and a ceiling does not reassess anything. It produces the same action for the patient whose metabolism makes 100 MME a modest dose and the patient for whom 40 is already dangerous.

The precautions themselves are sound. Closer follow-up, naloxone in the home, overdose education for the patient and the household — these are good practice. The argument is about when they are triggered: by an individualized judgment that risk is rising relative to benefit, or by an arithmetic line that knows nothing about the person it is being applied to.

What follows from this for a program

If the dose a person needs varies this much, then the useful thing to build is not a better threshold. It is a way to tell which patients are pharmacokinetic outliers and why — so that an unusual dose can be explained rather than merely flagged. That is what metabolic determination exists to do, and it is the difference between identifying outliers and marginalizing them.