Alternative Facts on Opioid Risk

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Morphine Equivalent Daily Dose Scores THIRD on Risk Scale!

While media muckrakers and anti-opioid zealots continue to fuel a fire of opiophobia and political strategists march like zombies in a parade of vote-seeking rhetoric, a simple fact remains ignored.  Morphine Equivalent Daily Dose (MEDD) equal to or above 100mg per day scores third on the risk scale for opioid-induced respiratory depression (OIRD).

Perhaps those that are in a position of adversely affecting millions of legitimate pain patients care less about their constituents than the validated ALTERNATIVE facts.

Government agencies and third party payers continue to employ MEDD limits while ignoring other equally or more important factors that influence risk of opioid-related deaths, including that opioid abuse does not equal long-term opioid use in legitimate patients.

Opioid dose alone is not at the top of the list for items that increase risk of opioid-induced respiratory depression.  And even if it were, as I’ve written about many times before (See The MEDD myth: the impact of pseudoscience on pain research and prescribing-guideline development), an opioid dose in one person is not necessarily equivalent to that same dose in another.1 Furthermore, there is no universally accepted morphine equivalent daily dose to make that calculation even if it were.

And, to make matters worse, the recently posted CDC online opioid calculator is grossly flawed for morphine to methadone conversions to the point of being dangerous. See examples below…

Guideline Resources: CDC Opioid Guideline Mobile App
“Morphine Equivalent” (mg) Methadone Daily Dose (mg)
80   20
168 21
320 40
410 41

Methadone conversion is quite complex and if a calculator is to be used, it must come with extensive warnings, be used only by experienced clinicians, and should consider the complex mathematics that should be built into the calculator as pointed out

I write this post today though to highlight that while all drugs, including opioids, have elevated toxicity as the doses increase, opioids are unique in that tolerance develops to various toxicities if the dose is escalated slowly, but there are well-known co-prescriptions that elevate the risks for all patients, opioid tolerant or not.

Today I wish to highlight an article not even off the press yet that really establishes the items we should be looking at to stratify risk for OIRD. Somewhere lost in the crossfire of anti-opioidism are these very real dangers that I believe are masked to patients and clinicians by a political veil.

In Zedler and colleagues’ recent article, it is clear that taking antidepressants and/or benzodiazepines carry a higher risk than 100mg MEDD.3  The latter is also well-supported by Dasgupta and colleagues who studied 2,182,374 chronic opioid patients and saw 478 overdose deaths (0.022% per year), 80% of whom received benzodiazepines together with opioids. In other words, rates of overdose death among those co-dispensed benzodiazepines and opioid analgesics were ten times higher.

Zedler and colleagues developed a Risk Index for Overdose or Serious Opioid-Induced Respiratory Depression (RIOSORD).4 This case-control analysis was based on a cohort of 18 million patients using prescription claims data. The authors identified 7234 cases of overdose or serious opioid-induced respiratory depression (OSORD) and compared them with 28,932 controls. Common risk factors associated with OSORD were assigned a score for each risk factor using multivariable logistic regression modeling. This RIOSORD tool for the general population is a 16-question survey, that has a total maximum score of 146 points. Of note, an automated software platform called Naloxotel was developed separately by *Remitigate, LLC and can be used by prescribing and dispensing clinicians to calculate percent risk based on the RIOSORD and creates a comprehensive electronic or PDF chart note that can help to justify co-prescribing naloxone for at risk patients.

With 90% confidence, the RIOSORD establishes that for patients taking opioids, concomitant antidepressants or benzodiazepines elevated the risk score higher than an MEDD exceeding 100mg per day. This can be seen in Table 3 of her publication and is pasted below for a quick look.

A prescription benzodiazepine?  9
A prescription antidepressant?    8
Is the patient’s current maximum prescribed opioid dose ≥100 mg morphine equivalents per day? (Include all prescription opioids consumed on a regular basis)  7

The original RIOSORD data was published with slightly different criteria in 2015 in a Veteran population.6 The RIOSORD discussed herein for the general population was presented in poster format two years ago at the American Academy of Pain Medicine Annual Meeting.

An ethical and moral question remains unanswered; Why do feeble journalists, politicians, and even some clinicians continue to hang their hats on MEDD alone while ignoring very real evidence that other factors are equally or more important?

LIMITED FACTS and poor evidence supports MEDD ≥100 mg alone as responsible for opioid deaths.

ALTERNATIVE FACTS provide real evidence that link several other factors to opioid-induced respiratory depression,
BENZODIAZEPINES or ANTIDEPRESSANTS have a higher risk than a morphine daily dose equivalent of 100mg/day or higher.

Seriously, can’t we just all get along for the benefit of patients and be truthful about these risks? I’d much rather see public service announcements and policy mandates that warn of the REAL and proven comorbid risks for OIRD rather than blaming opioid dose alone. Is anybody with me on this?

PLEASE feel free to post comments!



  1. Fudin, Jeffrey, Jacqueline Pratt Cleary, and Michael E. Schatman. “The MEDD myth: the impact of pseudoscience on pain research and prescribing-guideline development.” Journal of pain research 9 (2016): 153.
  2. Fudin J, Marcoux MD, Fudin JA. Mathematical Model For Methadone Conversion Examined. Practical Pain Management. 2012 September; 12(8): 46-51.
  3. Zedler B, Saunders W, Joyce A, Vick C, Murrelle L. Validation of a screening risk index for serious prescription opioid-induced respiratory depression or overdose in a U.S. commercial health plan claims database. Pain Medicine. 2017; In press.
  4. Dasgupta, Nabarun, et al. “Cohort study of the impact of high-dose opioid analgesics on overdose mortality.” Pain medicine 17.1 (2016): 85-98.
  5. Zedler, Barbara, et al. “Validation of a Screening Questionnaire for Serious Prescription Opioid-induced Respiratory Depression or Overdose.” Pain Medicine 16.3 (2015):5.
  6. Zedler, Barbara, et al. “Development of a Risk Index for Serious Prescription Opioid‐Induced Respiratory Depression or Overdose in Veterans’ Health Administration Patients.” Pain Medicine 16.8 (2015): 1566-1579.

*Author Dr. Jeffrey Fudin is President and Director, Scientific and Clinical Affairs for Remitigate, LLC


13 thoughts on “Alternative Facts on Opioid Risk

  1. So a bit of history i am 35 have had 6 major operations before the age of 18 due to sports torn petela tendon broken leg screws and staple put it back together. I started taking Lortab 5mg in 2002 at age 20, this is after injections, physical therapy, lidocane patches extra. went to college got a degree in psychology all while on 5mg of Lortab. Then in 2006 graduated got a job my pain increased due to more athritice setting in and nerve pain in leg so i was upped to 7.5mg stayed on that for 2yrs. got married good job injured my knee torn meniscus, then got put on oxycodone 10mg 4 times a day waiting to get surgery.
    the economy tanked in 2008 -2009 lost my job had to put off surgery but the meds helped so i was not that worried. stayed on percacet 10mg for a year in the same pain management clinic i had been goin to for 8 years now. so my visit like any other i thought turned out to be a nightmare my doc says “ you need to havd your knee operated on asap or i cant treat you any more. i said why what is this about. he said with the new laws and the DEA cracking down and you being so young 26 i can’t treat you anymore so here is 1 week supply of your meds and get into an orthopedic doc and that was my visit and he walked out. so i call my orthopedic right after i got out and they said we cant get u in for 3 weeks i explain my situation they say sorry and i scheduled it for 3 weeks out.
    I run out of my meds after 2 weeks trying to streach them have horrible withdrawals. finally get over those go to my orthopedic and ask him if he can help with my pain he says sorry i cant give you anything unless we do the surgery, i still have no insurance at this point. so he gives me a prescription for ibuprofen and a referral to a pain clinic. call that place up cant get in for 4 weeks and they want an updated mri so now im borrowing hundreds of dollars from my parents. get the mri go to the pain doc and he tells me the same thing your to young i can only give u tramadol. taken that before hardly works for me. so now im at my breaking point and an old high school friend i know gives me some oxycodone 15mg he gets from a guy. i break it in half and take it finally some relief. i get it from my friend for two weeks while trying to get into another pain clinic. I get into this clinic and it works out i get a very understanding doctor who puts me back on 10mg percacet. then the pharmacy’s start treating me like a drug addict everytime i go in to get my meds or i have to drive to 10 diffrent places just to get it filled. I have been treated like an addict have been looked down on by my family and friends all because of injuries that happened when i was a teen. now with more restrictions by the government and more negative media attention its just getting worse. we are not junkies, we are regular people looking to live our lives with some dignity and a little less pain. I dont think that is too much to ask.

  2. I’ve just been diagnosed with stage 4 Melanoma. If I begin to experience pain that is left untreated, I will commit suicide rather than die a slow painful death. So, there’s the alternative.

  3. Mr Kaufman, “These people [Washington State Lobbyists] were busy being Donald Trump…before there was a Donald Trump”?? What does that even mean, lol? Trump did not create this problem nor did he agree to the laws, rules OR regulations created by and put into place by the previous administration and its elected officials, The problem in Wa. state? Washington is ALL democrat in its elected offices. throughout the state so ? Sounds to me like they were trying hard to Be [career] politicians that decide what is best for us with a *Blanket solution*, one that is “good for Everyone” (Obama care anyone?)
    This is a *Great* forum, please don’t take it down a notch by interjecting your *Personal political views, name calling and attaching blame where None (*happens) to be due to our sitting president–who, BTW has only been a politician for a number of months, unlike the career politicians who will make decisions based on “Donations” to their tax shelters. We have no idea his agenda for addressing this particular problem, at least I have not heard him speak on this issue. Obamacare ruined my insurance co. – one that took Excellent care of both myself and my spouse. (they were *forced into bankruptcy) leaving us both to fend for ourselves with Medicare. No more 12 million dollar ‘lifetime’ care reserve for each of us (for medical treatment), the Gift of Life I promised my wife’s mother!

  4. Oh my, I could write a book…there are so many moving parts to this whole faux-opiate ‘epidemic’, it is hard to know where to start.
    4 words explain the bulk of the ‘epidemic’…Baby Boomers, War Veterans. The Boomers have entered older age, and, just like every other generation to hit that age, are going to their doctors with the arthritis, the bad back, the bum knee.
    Only THIS time, it is the Baby Boomers, the largest demographic group in all of human history…so yes! There will be more of them. Lots more.

    We’ve been at war for years now, and every year more soldiers come back with injuries, and want (and deserve!) pain relief. There are also a lot of them. So you have two obvious explanations right there for the increased numbers…and also keep in mind that those soldiers tend to be younger (we don’t send older folks to war, we send our kids..) so you’re going to see downward pressures on the age groups being affected…or, as the MSM headlines would scream, “The Opiate Epidemic Is Killing Our Children!”

    One more point I’ll raise here is the role of Big Pharma and their patented ‘Franken-drugs’…media coverage focuses on the irresponsibility these companies showed in marketing their creations…MARKETING! As if there were nothing wrong with DEVELOPING such drugs in the first place!

    And WHY did they develop them, when they did? Obviously they were trying to front-run the coming Boomer transition to old age, with a new, PATENTABLE opiate they could market to doctors and patients. Because let’s face it…nobody is going to make bank on granny getting a bottle of generic Vicodin from her doctor. Before these drugs came along, opiates that powerful were only seen on burn units, etc, where they were highly restricted, regulated. But their little monsters have gotten away from them, haven’t they? And now we see all the fingerpointing, and poor granny can’t even get the damned Vicodin anymore because her doctor is afraid to prescribe it!

    But no one asks WHY these potent formulations were thought necessary, or questions the wisdom of allowing them to continue to be so freely made and marketed to the general public through their doctors. The difference between Vicodin and Fentanyl is like the difference between your home-brewed craft beer and laboratory-grade ethanol. Just imagine what the alcohol stats would start to look like if we allowed people to market beverages of 200 proof? Yeah, there MAY be a need for something like that, but certainly not on the shelves at your grocer…

    Well, I better stop. Between the carefully groomed ‘stats’, the endless litany of false ‘facts’ about these drugs, the outright demonization of them, and the growing chorus of those who have been and are being harmed by the phony drug-warriors, I’d be here all day, and this would be one epic post!

  5. Hi everyone! I am new to this blog and, for that matter, any blog at all. In the last 8 years I was rather busy defending my name and my speciality of pain management in the court of federal law. A bottom line of this discussion, in my humble opinion, is rather simple and straightforward. The east majority of doctors is too intimidated by the government to do what is right and, fearing a prosecution, refuse to follow their Hippocratic oath to alleviate their patients suffer. They would rather do nothing than risk their own career and, under the pretense of false guidelines and regulations are staying away from their professional obligations. The main casualitis of this war on drugs are those millions of people in pain and our professional reputation. Will this situation get better? Probably not in our lifetime.

    Epidemic of drug overdose? How about these 250.000 who die every year of alcohol abuse or 450.000 of cigarettes? Do not hear much of this statistics!
    Joseph ZOLOt, MD.

  6. Chronic pain patients are taking their lives due to under or untreated pain which is exactly what our government seems to want! So MANY lies by the CDC tat they should ALL be fired! I am tired of seeing peopel lose their quality of life in the name of saving soem 40,000 addicts andnothing against the addicts but there is NO epidemic! I say again there is NO epidemic! There are 250,000 medical error deaths each year so, if 40,000 is an epidemic then those 250,000 are REALLY an epidemic of huge purportions! There is another agenda here folks follow the money it is always about money! Shame ont he media for fueing this without telling how chronic pain patients and their families are paying the steepest price! Opiates have successfully reated chronic pain for hundreds of years and now the CDC claims they are not! I call BS! The CDC used literature and a team of drug addiction industry zealots to come up with the ridiculous guidelines! Whos pockets are beign filled???

  7. I am not certain how do I should address you Ms. Kirby, whether it’s Dr. Kirby or Mrs. Kirby, but your posts yesterday resonate like a bell. I mean no offense.

    I think the problem really now is that the work of the anti-opiate crowd has stirred up a hornets nest of anti-opiate groups that like a symbiotic kind of chain is strangling the last best hope for patients suffering with intractable pain. What is really going to be the deathblow to the ongoing prescribing of these meds will come into two forms. The first will likely be Medicare implementing the CDC guidelines excluding only palliative care and the second is that doctors are overwhelmingly supporting this adoption.

    One only has to look at the state of Maine. If you’re not aware, Maine as of January 1 began a program was a goal that by June 1 no one in the state -unless they’re suffering from cancer or on the palliative care service- can be On doses greater than 100 mg equivalent of morphine. As an aside three quarters of those patients (or at least a substantial majority clothes ) Are on Medicaid. In one fell swoop the government through his actions by June 1 will be eliminating the availability of opioids to a substantial number of poor people but at the same time saving millions of dollars from its tax expenditure pool. In other words the least among us, pain patients, especially those who are poor, will lose access to medication while at the same time the state coffers will remain fuller than they had been in years past. Once this trick is learned in the Governors conference this effort will be absorbed by state after state.

    What is really heartbreaking here is that in a survey of physicians 90% supported this bill. We usually can’t get 90% of physicians to agree to anything but the fact that 90% agree with this tells us that over the last decade we’ve lost the support of the medical community. One can only imagine what the ramifications of this will be for prescribers. The insurance industry will further adopt what the government adopts; media emboldened to continue the anti-opiate hype using the fact that the majority of doctors that agree these medications are bad (otherwise they would not support the limits)

    One last thing: There’s a Netflix documentary entitled Dr. Feelgood. I encourage you and others to watch this video. It is the attitudes of regulators, law enforcement officer, some physicians especially addictionologist captured by this documentary that have made me so pessimistic. As an aside I’ve been accused of typically being a Pollyanna-ish sort of soul. But that is now gone.

    Thanks for your post things: they inspired me to write this today; and, thanks Jeff for the opportunity to post these things

    Mike Brennan

  8. One last remark. My dad died of cancer before all this started. He was in sooo much pain. And he was so confused and depressed when he found out he was leaving us within the next 3-6 months. He was allowed pain medicine. But if it had been today and he was denied pain relief, I guess I would be in jail because there would have been a fist fight right there at the hospital (or worse).

    And in response to their allegation that opioids don’t work on a long-term basis, I have this to add. My mother in law suffered from multiple auto immune diseases and used pain medicine responsibly for decades … from the time I met her until the time she died from a mis-diagosed heart attack some 20 years later. Because of opioids, my kids were able to do things with her, she accompanied us on family vacations, and she led a good life and her grandkids remember her fondly and miss her deeply. So I don’t buy their allegation that opioids aren’t effective for long-term pain control. None of their studies go back that far, but my memory does.

  9. These people have their minds made up. Kolodny successfully launched and carried out a massive smear campaign against anyone and everyone who was prescribed opiates for any and all reasons, whether the risks outweigh the benefits or not. I am a chronic pain patient advocate. Once “War” was declared, there was no further input from CPP’s, nor was there ever an opportunity to even sit in and give input into any meetings regarding the subject. The truth is now coming out that prescription opioids is not the cause of heroin abuse … but you won’t see that information coming out with the robust push that the opioid frenzy was given. Thousands of letters written from thousands of people have gone unanswered and face to face meetings have been refused.

    Now … with Christie at the wheel … things are even worse. Christie once walked right past a New Jersey dad who passed him on the street with his very young daughter who needed medical marijuana for seisures and Christie wouldn’t even make eye contact with them. The dad moved to Colorado to get help for his daughter. The situation is deplorable. More and more people are talking about suicide because there is no relief in sight. I have people who have relatives who have died for lack of supervision after physician abandonment after being stable on well-monitored pain management programs for 8 years or more. I know people who have gone through many complicated surgeries with no pain medicine whatsoever. It always baffled me how the opioid committe could publish articles bragging on their accomplishments while pictures with their smiling faces have alcoholic beverages at everyone’s seat at the table. Do you suppose they all took cabs home?

    The State of New Jersey has doctors so afraid that oncologists won’t write a prescription for pain control while people are in end-of-life cancer stage. The one thing that is offered, in some states, is physician assisted suicide, assuming, of course, that the patient is willing to push the life-ending dosage needle themselves. My cancer patient KNEW what pain meds worked for him but the only thing that was offered was methadone. When he became confused at night, his wife had to put locks on the doors to keep him in at night. He was told that if he would give up all measures to fight the cancer, he would be hooked up with whatever medicine he wanted. (Nice trade-off.) Another New Jersey husband was very functional on a pain regimen that worked for him and when he was suddenly discontinued, he went to bedbound, got bed sores on the bottom of both feet, and has become withdrawn and non-responsive even to his wife. It’s pretty bad when people who can, have to move to another location for medical care, or worse yet, people who don’t have that option suffer and lose what functioning they had before the “War”. I have a Michigan patient who has lost all muscle tone due to hip surgery with complications of bone marrow infection and was given Tylenol to control the pain. How is rehab supposed to occur if you can’t get enough pain control to get up and about? I could give you hundreds of other examples if time and space would permit. To my knowledge, a chronic pain management doctor has never been involved in any of their decision-making. I guess chronic pain patients should be labeled “the forgotten ones”. Pass the laws and forget them. We have no voice.

    I’ve had the same Indiana PCP (before moving to Florida) since my mid-20’s and we always go through all my meds and how they’re working for me. Adjustments were made any time we could discontinue anything. And here I am, 35 years later, having moved to Florida, and my doctors here have but one objective … to get me off all medicine … with only passive remarks that all my problems are likely “caused” by medicine. I’m a retired paralegal and U.S. District Court worker and had a very successful carreer. Do they now expect me to believe that the medicine was the cause, and not the best course of medical treatment for me? If so, then how in the world did I survive such a successful career in the legal field. My doctor of 35 years is a doctor AND a pharmaist. He does nothing but study medical conditions and pharmacy issues. He doesn’t even own a television. I’d challenge any of these so-called “experts” or lawmakers to say the same. These people need to think it over hard and ask themselves if this is really what they wanted. Really???

  10. I’d really rather that we take a close look at the medication roulette that is occurring with the prescribing of these medications so that we could learn.
    Differential risk assessment based on patient characteristics, history, and their illness course and diagnoses is not occurring in any kind of systematic way and that creates an additional confound that impairs our understandings.
    I truly respect and thank you for leading us back to this conversation always.
    Just saying…thanks.

    1. Terri, as long as the anti-opioid zealots continue to dominate prescribing guideline committees, we’ll continue to get intentionally disingenuous, invalid, and highly unethical guidelines. I’ve been in way too many meetings with these incredibly dishonest pseudoscientists. Irrespective of how black-and-white a brush one uses to paint the picture of the falsehoods that they perpetuate, they’ll tell you that you’re “crazy”. This happened in the Washington State Guideline Committee meetings a couple of years ago, when they insisted that MEDD was valid, refusing to pay attention to my recommendation that pharmacogenomic differences should be noted in the guideline. These people were busy being Donald Trump…..before there was a Donald Trump! Great job, as always, Jeff.

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