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The ‘science’ behind 90MME as the upper limit for opioids prescribed for chronic pain

In 2016 the US Centers for Disease control (CDC) released guidelines on the prescribing of opioids for chronic pain in an effort to reduce opioid overdose deaths.  These guidelines had disastrous consequences for US chronic non-cancer pain (CNCP) patients, many of whom were force tapered off their opioid pain relieving medications to their great detriment.  People who had previously been functioning well on these mediations were now back in terrible, daily pain.  Some lost their careers, their relationships, their social lives, and some attempted or completed suicide.

It was a travesty.

Despite the recognition that while opioid prescriptions for chronic pain have plummeted, overdose rates are still soaring, the fear of opioid overdose spread world-wide, with other countries updating their opioid prescribing guidelines for CNCP patients. Canada, Australia, the UK, all force tapered patients off opioids, citing the reasons put forward by the CDC.  Not surprisingly, the results were the same in these countries, CNCP patients were abandoned and force-tapered and most lost their quality of life.  Some lost their lives.

Adding insult to injury is an examination of the factors that led to the infamous 2016 guidelines and the flawed ideas and disturbingly flimsy ‘science’ they are based upon.

One of the guiding principles of the 2016 regulations was the idea that the higher the dose of opioid medication, the higher the risk of overdose and/or death.  To calculate that risk, all opioids are first converted to milligrams of morphine equivalent (MME) or the amount of any opioid pain medication in milligrams that would be the equivalent of 1mg of morphine.   A set of tables were developed comparing all opioid medications and providing a formula to convert each opioid to its morphine dose equivalent.

It’s a simple calculation.  For example, according to the tables, oxycodone is 1.5 times stronger than morphine.  To calculate the MME of 10mg of oxycodone, you need to multiple 10mg by 1.5, which gives you 15mg of morphine.  Fifteen milligrams of morphine is equivalent to 10mg of oxycodone. 

MMEs are used in pain management to transition patients from one opioid to another at an equivalent dose, and they are used in research to attempt to standardise and compare data on opioid medication doses when using different opioid medications.

In terms of overdose risk, it was said that doses over 50MME substantially increased the risk of overdose or death and higher than 90MME should not be prescribed as the risk outweighs the benefit.

This was also based on flawed science, but we’ll come to that.

First, how did the 50MME and 90MME come about?

The idea of limiting opioid prescriptions to less than 90MME per day comes from a group of very small studies, the most influential of which was a study by Bohnert et al in 2011 “Association Between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths”

That study followed around 150,000 patients taking opioids long-term between 2004 and 2008 and found that the overdose rate was correlated with higher doses of opioids. That is, opioid overdoses happened more often at doses over 90MME.   The media picked this up and ran with it.

But.

On reading the study, the actual fatal overdose rate was 0.04%.

0.04%. 

So yes, those on higher doses overdosed more often. But overdose is not a common event, it is in fact a very, very rare event.   But you’d never know that because the researchers and the media did NOT report that only 0.04% of chronic pain patients overdosed and died.   Because that doesn’t make a good headline and that won’t generate clicks.

Far more appalling, and far more dangerous, is that the CDC used this study as the basis for their assertions that higher doses of opioids lead to a much higher risk of overdoes and therefore doses over 90MME should NEVER be prescribed. 

The CDC was clearly aware that overdose is rare in chronic pain patients, but they chose to ignore that fact, and publicised that overdoses are more common at higher doses.  They cherry-picked the data to make it say what they wanted it to say.  And the parts that didn’t suit their narrative? They simply didn’t mention them.

I have found this practice of selective reporting and cherry-picking of data is shockingly commonplace in research and media coverage of opioid prescribing for chronic pain.

A follow-up study, also by Bohnert, showed that the median overdose dose was 60MME and that 86% of all overdoses occurred on doses lower than 90MME. 

Let’s read that again.  Most overdoses, 86% of overdoses, occurred at dosages lower than 90MME.

Does this not mean that doses of less than 90MME are more dangerous?  No, it doesn’t. It’s a function of the fact that most opioid prescriptions are for less than 90MME daily.  There are simply more prescriptions written for less than 90MM daily, which means there are more overdoses at less than 90MME daily. But again, I’m illustrating how one line can be taken from a study and it can be interpreted, either accidentally or on purpose, to say something that proper analysis of the data does not support. 

It’s convenient for policymakers to try and homogenise everything, to fit it into nice, neat boxes, but opioid prescribing and chronic pain does not work that way. It’s not accurate, it’s not meaningful.  It’s junk science.  When a policy is based on junk science the policy itself must be junk.  One leads directly to the other.  

But it isn’t policymakers who are suffering, it is chronic pain patients.  Most specifically those with the worst pain, the most severe pain, those who rely on opioid pain relief because of the severity of their daily pain.   This policy targeted and punished the people who are already amongst the most vulnerable in our society. 

In Australia, our opioid prescribing guidelines were changed in June 2020.  There was little consultation, and most GPs and even pain management doctors were taken unawares.   The implementation was very poor, there was much confusion around the actual requirements, messaging was mixed.  The changes were also brought in in the middle of a pandemic. Faced with these changes many GPs ‘fixed’ the problem by simply refusing to prescribe opioids at all.  The quickest, easiest fix for overburdened time-poor GPs.  It became commonplace to see signs in GP waiting rooms stating that ‘this practice does not prescribe opioids’.   Rather than wade through the new requirements, chronic pain patients on long-term opioid therapy became highly stigmatised and were refused care.

In 2021 I moved to a new area and needed to find a new GP.  I was personally refused care by six GPs, because they would not accept a patient who was on long-term opioid therapy. I was advised to taper off my opioids and come back then. Like all other chronic pain patients in this situation, I was treated like an addict, my pain was dismissed and I had no recourse. I had no choice but to keep looking and I did eventually find a GP who would take on my care. But it was an expensive and demeaning experience.

In the US, over time, it became clear that chronic pain patients were being harmed by the misinterpretation of the guidelines.  In 2019 the authors of the CDC guidelines put out a media statement advising against the misapplication of their 2016 guidelines in an attempt to clarify their intent and to combat the forced tapering of chronic pain patients.  This media statement included statements specifically addressing the 90MME ceiling and that it should not be used as a hard limit, and renouncing the forced tapering or cutting off of chronic pain patients:

Misapplication of the Guideline’s dosage recommendation that results in hard limits or “cutting off” opioids. The Guideline states, “When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should… avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to ≥90 MME/day.” The recommendation statement does not suggest discontinuation of opioids already prescribed at higher dosages.“

The Guideline does not support abrupt tapering or sudden discontinuation of opioids.  These practices can result in severe opioid withdrawal symptoms including pain and psychological distress, and some patients might seek other sources of opioids. In addition, policies that mandate hard limits conflict with the Guideline’s emphasis on individualized assessment of the benefits and risks of opioids given the specific circumstances and unique needs of each patient.”

Also in 2019, the American Medical Association put out this statement in support of chronic pain patients and acknowledged that there is a need for long term opioid therapy at doses higher than 90MME:

“Our AMA affirms that some patients with acute or chronic pain can benefit from taking opioid pain medications at doses greater than generally recommended in the CDC Guideline for Prescribing Opioids for Chronic Pain and that such care may be medically necessary and appropriate.”

And now in 2022, as a result of much advocacy work and campaigning by chronic pain patients and medical groups in the US, the CDC is updating its opioid prescribing guidelines for chronic pain. The new guidelines are online and currently available for comment.  Gone are all references to hard limits on prescribing doses or durations of treatment with a strong focus on individual treatment of chronic pain. The CDC have seen the error in their ways, and the suffering that their 2016 guidelines caused and are aiming to rectify that suffering.

But what about here in Australia?  As we blindly follow US policy, even as that policy is being repealed and openly acknowledged as flawed and harmful, chronic pain patients here are still being force tapered to below 90MME or off opioids completely.  Even patients who were doing well on a stable dose and where opioids clearly improved their quality of life.  There is now an epidemic of untreated and undertreated chronic pain in Australia, particularly in rural areas. 

Advocacy efforts for greater access to allied health services and to make those services affordable are to be lauded, but they imply that opioids can be replaced with physiotherapy or hydrotherapy or psychotherapy.  In the case of severe, daily chronic pain this is rarely the case.  Allied health treatments are helpful adjuncts, but opioids are, and likely always will be, an essential part of a multidisciplinary chronic pain treatment plan.

Most important of all, how long will it take Australian pain management specialists to update their knowledge and return to prescribing the lowest dose of opioid pain medication that controls a patient’s pain?  How long until they abandon the non-scientific and non-sensical upper limit of 90MM?  How long will Australian chronic pain patients continue to suffer?

5 thoughts on “The ‘science’ behind 90MME as the upper limit for opioids prescribed for chronic pain”

  1. The author needs to carefully define “dose” and specify the method of measurement. Is the “dose” the prescribed dose or the actual amount ingested? In the latter case, were the actual doses of dead patients measured by chemical analysis of blood samples? If the actual doses of dead patients were greater than the prescribed doses, we need to have a theoretical model of why these dead patients abused opioids. I submit that opioid abuse is strongly linked to the side effect of euphoria and euphoria is poorly correlated with analgesic strength, i.e., MME. It is well known that agonists of kappa opioid receptors, e.g., pentazocine, produce less euphoria than mu agonists and have a low potential for abuse as is reflected by a Schedule 4 classification by the DEA. Yet, the CDC treats 90 MME of pentazocine (243 mg) the same as 90 MME of oxycodone (60 mg). By the CDC’s logic, it is the same as 90 MME of heroin.

    1. Thanks for your comment, you raise a lot of very good points. I would submit that, in the case of chronic pain patient overdose, the reason for taking a higher dose than prescribed is usually to manage pain, not achieve a euphoric state. Opioids do not induce euphoria in long term opioid therapy for chronic pain.

  2. A couple things…in the article you refer to 0.04% and 0.4% so you may want to double check this number and update the article with the correct one consistently referenced. The other thing is that the CDC had a 90 MME limit recommendation for prescribing primary care physicians only and they did not intend it to apply to specialists treating patients in severe pain.

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