Sunday, October 6, 2019

Part 6 - Why Is Cancer Pain So Special?

by Drew Rosielle (@drosielle)

A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.

This is the 5th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:
Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses

Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph

Part 5 – Why Do We Lump The Non-Cancer Pain Syndromes Together?

This is Part 6, which asks the sort of inverse question to Part 5 – Why Is Cancer Pain So Special?

Why is cancer pain, in so many guidelines and organizational/public policies ‘exempted’ from the dosing and safety guidelines. This is not a rhetorical question – I have not actually ever read a coherent explanation as to why.

One might reasonably assume there’s all this research demonstrating the safety and efficacy of long-term opioid use in cancer patients. In reality, that research is non-existent.

Guidelines like the CDC’s accurately point out that there are essentially no data demonstrating the long term efficacy of opioids for ‘chronic non-cancer pain’ (CNCP). True enough.

But where is the study proving the long-term safety and efficacy of opioids for cancer pain? Where are the well-designed, controlled (or at the very least prospectively designed and closely monitored) studies of opioids for cancer pain which follows patients for longer than 6 months? It’s possible I’ve missed some key studies, but don’t think I have (but correct me in the comments if I have!).

Notably, there are a collection of studies like this one, all involving 6 months or longer of open-label monitoring after a RCT of an opioid for cancer pain. It’s middling quality data involving highly selected patients, and, importantly, for every study like this in the cancer world there’s a similar one like this one in involving CNCP patients. In other words, I don’t see that we are in a situation where we can say we have more convincing, higher quality data for cancer patients than non-cancer patients overall.

And, what exactly do we mean by ‘cancer pain?’ A patient with metastatic breast cancer to bone who has bone pain? I think most of us would consider their pain ‘cancer pain’? What about someone with severely painful multiple myeloma who achieves a long-term remission but their bone pain only partially resolves? Their X-rays and scans continue to show widespread lytic bone lesions, but they don’t have active myeloma. And they may go 5-10 years before relapse. Is that cancer pain?

What about someone with severe, non-healing, osteoradionecrosis of the jaw but no evidence of active oral cancer anymore? Let me tell you, that patient will have severe pain, potentially for life. What about the patient with breast cancer – does it matter she may live over 5 years even with widespread, painful bone metastases? Is that still ‘cancer pain’ (obviously it is), but if so why do we collectively seem to make an important difference between her and the patient who may also live many years with painful, nonhealing osteoradionecrosis? None of this is to mention chemotherapy induced peripheral neuropathies – are those cancer pain? I’m not proposing that I know the answer to these questions – what I’m trying to do however is to make clear that I don’t think we are operating with a set of really fuzzy, imprecise, and ill-defined concepts even when we say something like ‘cancer pain.’

So, I think about all this a lot, and here’s where my current thinking is.

First off, I’ve been trying to find the answer to the question why is cancer pain treated so much differently in these guidelines? Like I intimated above, I don’t actually believe it’s due to there being significantly more/better research data out there establishing the safety and efficacy of opioids for cancer pain than the CNCP syndromes. As I’ve been writing this, I did some rooting around to try to see if I was wrong, and didn’t find anything to change my mind about this. If you want to, dig through this list of Cochrane reviews on the subject, and then try to convince yourself that, in important ways, we have better data for cancer than non-cancer pain syndromes.

Is it because we believe cancer generally hurts more than other pain syndromes? I hope not, that is stupid and wrong.

Is it because we believe patients with cancer are more morally deserving of pain relief than others? Christ, I hope not.

Is it history? That cancer pain has a deep history of decades of advocacy internationally to normalize chronic opioid use for it which has been successful? Maybe, but opioids for CNCP advocacy also has a pretty deep history of advocacy too, and I don’t think this is enough to explain the difference.

Is it because there is something unique about the cause of pain in cancer that makes it reasonably more likely to respond well to opioids long-term than other syndromes? While acknowledging this remains speculative for all of us, I do think this idea at least has some basis in reality, but it only goes so far, and does not justify broad lumping of all the CNCP syndromes together, or all pain-from-cancer syndromes together. That is to say, for at least some of the cancer pain syndromes we encounter, patients, in pretty straight-forward way, have space forming, inflammatory, and infiltrative tumors causing the pain. Ie, the cause of the pain is from clinically obvious, direct, inflammation-heavy, tissue damage and destruction, and, arguably, pain from this etiology (let me call it ‘tissue damage pain’ for short here) responds better long-term to opioids than pain from other causes.

While I don’t think I can cite you clear research data to prove this, I myself basically believe this/accept it to be true: tissue damage pain responds pretty well to opioids, long-term. Obviously, for many CNCP syndromes there is not this ‘tissue damage’ etiology. However, there are many syndromes, ones I’d note that you see a lot if you care for people with serious illness, that do involve tissue damage – sickle cell disease, some types of chronic wound pain, some types of osteonecrosis, ischemic limb pain, possibly pain from some of the inflammatory arthritidies, etc. (Referring to ‘cancer pain’ scenarios I mentioned above, I don’t myself know how to really categorize the chronic bone pain in patients who have achieved remission for multiple myeloma. Is that ‘tissue damage pain’ as I’ve defined it? I’m not sure.)

So, if this is the reason we treat cancer pain as special, my basic request to the world is that we actually say what we mean, and replace cancer pain with something like ‘pain from active tissue damage.’ It’s a godawful mouthful I know, undoubtedly there’s a more euphonious term one can use, but hopefully you get my point. Maybe we should coin a new term: “inflammalgia?”

Finally, is cancer pain treated special because patients with cancer are assumed to be terminally ill? At the end of the day, I think this is actually the predominant reason cancer pain is exempted from all these guidelines. It’s the same reason ‘palliative care’ patients are exempted – it’s because the people who write these guidelines think we’re only caring for patients near the end of life.

To an extent, I do think the poor prognosis-basis for the difference has some merit. If someone has a short prognosis (I’m not going to define what that means but I know it when I see it), I think it’s a pretty uncontroversial statement that having a short prognosis markedly changes the benefit:risk ratio when it comes to opioids. While preservation of function is typically a goal until a patient is really in the final stages of life, for patients with terminal illness and severe pain the simple goal of aggressively relieving suffering is often paramount, and opioids do a really good job of that, especially in the short term. Additionally, the risks to a patient of a lot of the long-term pernicious effects of opioids are less if time is short.

Makes sense to me, but I worry about an unexpected effect of exempting cancer pain from these guidelines and discussions: it gives some people the sense that opioids are unquestionably indicated for patients with cancer and we don’t really have to worry about pain. I’ve seen many situations in which a patient clearly has a dangerous OUD, who has pain and cancer, and people just keep on prescribing. Or, worse, a patient is clearly diverting and people just keep prescribing because 'they have cancer and we have to treat the pain, right?' You encounter the attitude also of 'well they’re dying so who really cares', which makes me want to vomit, as if addiction is a pleasurable thing for people and a great time for a family and not anything other than a tremendous source of total suffering, although I’m happy to say that lately it’s mostly been patients saying that to me ("I have cancer you have to give me meds. Who cares I’m dying anyway"), not my colleagues.

Fundamentally, I’m not really arguing that the policies or guidelines should be rewritten to lump cancer pain and CNCP together. Selfishly, we already waste a ton of time in my clinic begging to get opioids covered for my patients as it is, even for dying cancer patients, and I don’t want anything to happen to make that harder. Mostly I’m arguing the great split between cancer and noncancer pain is harmful because it encourages fuzzy thinking about risk in cancer patients, and lumps too many unrelated non-cancer pain syndromes together, in ways that are really harmful for people, and encourages clinicians and policy makers to think about, eg, a 60 year old patient with severe degenerative arthritis who can’t get out of bed due to pain with a 60 year old patient with depression, anxiety, a history of alcohol use disorder, and ill-defined chronic abdominal pain and headaches in the same category.

It encourages us to simplify what is complex, and our patients deserve better.

Thanks for listening,
--Drew.

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph
Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph
Part 5 – Why Do We Lump The Non-Cancer Pain Syndromes Together?
Part 6 - Why Is Cancer Pain So Special?

For more Pallimed posts about opioids.
For more Pallimed posts by Dr. Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

Sunday, October 6, 2019 by Drew Rosielle MD ·

Part 5 - Why Do We Lump the Non-Cancer Pain Syndromes Together?

by Drew Rosielle (@drosielle)

A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.

This is the 5th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:
Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses

Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph

This is Part 5 – Why Do We Lump The Non-Cancer Pain Syndromes Together? Part 6 is heavily related to Part 5, and will ask the sort of inverse to Part 5 – Why Is Cancer Pain So Special?

The language we use to categorize pain and talk about pain is inadequate, dangerous, and unfair.

In particular what I mean here are the distinctions made between ‘chronic pain’ and ‘cancer pain.’

What is actually meant by chronic pain? In the very important CDC opioid guidelines, they use this definition: “Chronic pain has been variably defined but is defined within this guideline as pain that typically lasts at least 3 months or past the time of normal tissue healing.” Most definitions use something like that. Note that the definition really focuses on the temporality of the pain, which is of course important, but really makes no proposal otherwise on what the pain syndrome is, what its course is, what causes it, what the patient’s prognosis is, whether or not it involves a primary ongoing lesion of the nervous system or ongoing active tissue inflammation and damage (eg, chronic rheumatoid arthritis pain, chronic sickle cell pain, etc, which can continue for years), etc.

What this leads to is a broad lumping together of dozens of different pain syndromes into a single category: ‘chronic pain,’ or ‘chronic non-cancer pain’ (I’ll just say CNCP here for brevity).

Reading guidelines like the CDC’s, they basically apply themselves to all CNCP, with a brief, unexplained exception for patients with cancer pain, or who are receiving palliative care, whatthehellever that means.

Which essentially means in those guidelines, and in all the policy responses to them (by payors, state medical and pharmacy boards, local health organizations implementing new policies, etc), all CNCP syndromes are lumped together.

Think about this. From a policy standpoint it treats chronic pain from fibromyalgia, work-related back injuries, chronic headaches, severe inflammatory arthritidies, poorly defined chronic abdominal and pelvic pain syndromes, moderate degenerative arthritis, bone on bone deforming degenerative arthritis, sickle cell disease, congenital spine deformities like severe scoliosis, spasticity syndromes like multiple sclerosis or cerebral palsy, chronic bone diseases like osteonecrosis, chronic ischemic limb pain, chronic wound pain, post-surgical neuralgias, complex regional pain syndrome, the dozens of types of axonal neuropathies, etc., as the same thing (from a policy standpoint).

You get my point, I hope, which is to argue that many of these are very different pain syndromes, which have different prognoses and ranges/types of treatments, and regardless of anything else, should not be lumped together without qualification with the couple syndromes that we do in fact have half-way decent-ish research data showing that opioids aren’t effective (for most patients), (long-term), (eg, chronic back pain, fibromyalgia, chronic headache syndromes). This is not me arguing that opioids are the best or first-line analgesic for many of the other pain syndromes (!), but more to point out that highly influential guidelines or organizational/public policies which do not differentiate between, say, the patient lacking cartilage in most of their weight-bearing large joints who has trouble taking the dog out to pee without a few hydrocodone a day (who’s tried many other modalities also), and the depressed, unemployed patient with a work-related back injury who drinks to intoxication most days a week and is on long-term opioid therapy (which has not been successful to restore function), is a shit guideline/policy.

I can’t see a clinically coherent or fair reason to do this lumping, except that these things aren’t ‘cancer pain’ (see the next post on this). Like everything, it’s complex, and what we need are thoughtful, skilled clinicians who are knowledgeable and who can perform individualized assessments and treatment planning with patients, not one-size-fits-all lumping, but these policies and guidelines discourage that, regardless of their authors stated intentions (I don’t care what their intentions were), and that’s crap.


Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph
Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph

For more Pallimed posts about opioids.
For more Pallimed posts by Dr. Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

by Drew Rosielle MD ·

Saturday, October 5, 2019

Part 4 - Everything We Were Taught About High Doses Was Wrong, and the Same Hand-Crafted Graph

by Drew Rosielle (@drosielle)

A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.

This is the 4th post in a series about opioids, with a focus on how my thinking about opioids has changed over the years. See also:

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses

Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph


This is Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph

I no longer consider opioid dosing and conversions as a linear matter. That is, my approach to both opioid dose adjustments and rotations changes markedly the higher the dose of opioid a patient is on.

Most of us have long been familiar with the idea that methadone’s ‘equianalgesic’ relationship to other opioids is non-linear. Ie, the higher the dose of another opioid you’re on, methadone becomes relatively more potent (you use relatively less methadone) – the equianalgesic ratio changes.

I now believe this is true of all opioids both with conversions and with titrations, and I imagine a lot of you believe this too.

To give you an example: if someone is on 4 mg of oral hydromorphone PRN and has severe uncontrolled pain, there’s a decent chance I’d increase them to 8 mg if they’re otherwise doing ok, and if I did I wouldn’t spend much time worrying about that decision. If someone is on 40 mg of oral hydromorphone PRN – while what I would end up doing is a highly individualized decision, let me tell you I would 100% think twice before increasing them to 80 mg. In fact, I’d be extraordinarily unlikely to do that, whereas I just wouldn’t hesitate to double a similar patient from 4 to 8 mg. Ie, despite all the textbooks saying we should increase opioids in percentile increments I don’t believe that once I’m working with high doses. It Is Not Linear.

And I bet a lot a lot of you reading this would agree – you’d, at least, hesitate. And I’ve been asking myself why, and again I think part of it is my recognition that very high doses are rarely effective, or at the very least changes at the very high range of opioid dosing are far less effective than in the low range (see my last post and its lovely hand-made graphic which I’m reproducing here), and that the benefit:hazard ratio of escalating at very high doses is far lower than with low dose opioids. (About that benefit: hazard ratio – for well monitored, highly opioid tolerant patients I’m not arguing that the risk of harmful overdose is very high for these patients, in my experience it isn’t and opioid tolerance is a truly remarkable thing. I’m more arguing that the benefit to patients from dose escalations for patients already in the very high range are very small, and much smaller for the typical patient when you, say, increase their morphine ER from 15 mg to 30 mg).



Regardless of the reasons underlying it, my point here is that I do, and I think most people do, think of these ratios, and these rules of dose titration, differently at high doses than at lower/moderate doses, although I’ve never yet read that anywhere, and I don’t really understand why because my impression is that this is common practice.

Same with drug rotation.

There’s been a lot of speculation with methadone – why it seems to be more potent the higher the baseline opioid someone is on and some of the speculation is that patients are hyperalgesic from the baseline opioid, and since methadone perhaps directly counteracts some of that hyperalgesia or at the very least doesn’t contribute to it much, it can be surprisingly potent. Eg, we can get away with such small doses of methadone sometimes because a patient’s baseline opioid dose was largely there just to overcome the hyperalgesia from that very baseline opioid. If that’s the case, then you could also imagine a scenario where the same phenomenon would obtain, at least to an extent, with rotating away from any opioid at a very high dose, not just methadone. To an extent: other commonly used opioids don’t theoretically counteract tolerance and hyperalgesia in the way we believe methadone does, but nonetheless it’s a sort of ‘partial-cross tolerance’ phenomenon. Ie, going from, say, high dose hydromorphone to morphine, perhaps you don’t have as much hyperalgesia initially from that morphine so you can get away with lower relative morphine dose. I need to stress this is speculation, I do not understand the mechanism here, but am more observing that the speculative explanation we have about why it seems to work for methadone could partially apply to any opioid rotation.

I don’t think any of this is extraordinary, however I’ll also add that I haven’t really seen any of this in a textbook, or as an asterix in opioid conversion tables (with the exception of methadone).

Consider this example: I remember every pretty early on in my career, having people on something like 10 mg/hr continuous hydromorphone infusions and needing to transition them off the IVs and doing the math and feeling the acid and bile rise to the back of my mouth. Eg 10 mg/hr = 240 mg/24 h = 4800 mg OME (by most equianalgesic tables). Even if you reduced ‘for incomplete cross tolerance’ by a whopping 75% (which, I’ll note, is more than most textbooks ever mention) that would still be putting someone on, eg, MSContin 600 mg twice a day. Like, whoa. Like, would any of you do that? Even if you use the so-called ‘new’ ratios based off the excellent MD Anderson study looking at IV hydromorphone to PO med ratios, that suggests a ratio of 1 mg hydromorphone : 10 mg PO morphine, which would be 2400 mg of morphine a day. And, note, that study calculated the ratio based on the final dose of what the patient actually ended up on, so if we use this as a conversion ratio the implication is you don’t need to account further for incomplete cross tolerance, which would suggest in fact we put this patient on 1200 mg of morphine ER bid.

LOL/puke.

(Now that I prescribe methadone…we didn’t prescribe it much where I started my career…I just put them on something like 10 mg tid of methadone and continue to be delighted that *most* of the time it goes just fine.)

But here’s the point: even before I routinely used methadone in these situations, I still ended up putting people on far lower doses than any textbook/consensus guidelines would recommend, maybe something like 120 mg tid of morphine ER and was surprised at how it went ok much of the time. Patients were ok (not perfect, adjustments were needed, but the rotation was not a catastrophe) with what is technically a massive dose reduction.

Why can we ‘get away’ with stuff like this? We can speculate all we want why but we don’t know, but I’m still going to make an empirical claim that the so-called equianalgesic ratios don’t apply at high doses.

They are worse than worthless, they are dangerous.

When I talk with people around the country about this, most people I talk with are doing just what I describe above. So, I don’t think I’m describing a particularly novel or extraordinary clinical approach.

What I’m more interested in is why we still talk about methadone’s non-linear conversion curve as something unique, when it isn’t (methadone’s curve is probably more pronounced than with other opioids, but the fact that it has a curve is not). By acting like methadone’s all fancy and unique, and by putting out equianalgesic charts and dose adjustment rules (eg the 25-50-100% rule) that don’t qualify that perhaps none of this applies to patients on very high doses, I think we are promoting unsafe practices. To an extent, most patients on very high doses are being cared for by specialists, and most of us know what we’re doing, so we have that safety buffer, but that doesn’t seem like enough

Most fellowship years, a few months into it, a fellow comes to me as they are figuring this out, and I have to break the news to them that most of us throw those tables out for patients on very high doses, and it’s kind of like breaking bad news to them, and I start telling them the truth, is that I sometimes don’t even bother doing the math when people are on really high doses, and half the time just ask myself Is there any reason not to put this patient on 10 mg of methadone tid? and nothing else.

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph
Part 4 – Everything We Were Taught About High Doses Was Wrong, And The Same Hand-Crafted Graph
Part 5 – Why Do We Lump The Non-Cancer Pain Syndromes Together?
Part 6 - Why Is Cancer Pain So Special?

For more Pallimed posts about opioids.
For more Pallimed posts by Dr. Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

Saturday, October 5, 2019 by Drew Rosielle MD ·

Friday, October 4, 2019

Part 3 - Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

by Drew Rosielle (@drosielle)

A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.

This is the 3rd post in a series about opioid, with a focus on how my thinking about opioids has changed over the years. See also:

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses





This is Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

I believed, and was taught, opioids had no intrinsic ceiling effect, and didn't think there was much difference between someone being on 100 mg of morphine a day or 1000 mg. I wish this was the case, but the number of patients I can recall the last 20 years who were on very high opioid doses who were doing 'great' (had excellent pain relief leading to important functional improvements and minimal side effects) is minimal (but not zero, mind you). Like, less than 5% of patients I’ve placed on very high doses. (I’ll be the first to admit I don’t have an exact definition of what that is, I don’t think that’s possible, but generally I’m talking about many hundreds of morphine milligram equivalents a day.) Most patients remained in terrible pain and had significant, ongoing disability despite the high doses (and undoubtedly for some of them because of the high doses). I’d increase someone’s dose, they’d report they’d feel better, but within a few weeks or months they’d continue to report daily, severe pain, and function would not have improved. I saw this pattern again and again. They weren’t overdosing, most of them were fine from a safety standpoint, they just weren’t helped by me pushing their doses into the very high range. As I look back on this, it’s bizarre to me I didn’t see more clearly in the past just how poorly most of my patients on high doses were doing. How I ignored that little voice inside of me which said, “Drew, they’re already on many hundreds of milligrams a day, they continue to report daily, severe pain…opioids are not helping them anymore.”

So much so that I’ve mostly stopped prescribing opioids, long-term, in those ranges, outside of patients who are dying and the care goals are really centered around alleviating suffering in those final days/weeks. (I use those doses short term during hospitalizations for pain crises.)

I should note here that I don’t think it’s helpful to calculate ‘morphine equivalents’ for someone on methadone for pain. I know people do it, but I don’t, and I personally think it’s a folly, it’s too much comparing apples and oranges, and the fact we know how to convert someone from methadone to a ‘typical’ opioid without killing them is a different thing than being able to speak confidently along the lines of “40 mg a day of oral methadone is equivalent to X mg a day of oral morphine.” Like, does anyone think they’ve got a good grip on that (if you do, please comment)? That’s not a question I’ve asked myself for years now because I don’t think it has an answer, and I think it’s a different question than “what is a safe and reasonable dose of oral morphine to convert someone to a day who is on 40 mg of methadone daily.” Part of this is because I think a lot of what’s pernicious about commonly used non-methadone opioids really comes out at higher doses (see my next post in this series), and I think those pernicious phenomena are really muted for methadone, and as I think about patients I have different categories in my head for patients on, saying, hundreds of milligrams of morphine a day who’s doing poorly (not getting good pain relief), and someone who’s on quite a high dose of methadone who’s not getting good pain relief. To me, those are different situations, whereas there’s not much of a difference in my brain’s way of categorizing the world between someone doing poorly on very high dose morphine and oxycodone, for instance.



So, I believe patients absolutely have a therapeutic ceiling effect with opioids, and at doses that are lower than I realized years ago, although everyone’s ceiling is different, but that should not be much of a surprise.

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

For more Pallimed posts about opioids.
For more Pallimed posts by Dr. Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

Friday, October 4, 2019 by Drew Rosielle MD ·

Thursday, October 3, 2019

Part 2 - We Were Wrong 20 Years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses

by Drew Rosielle (@drosielle)

This is the second in a series of several posts about many aspects of my current thinking about opioids.

The first post is here: Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

Over-prescribing fueled the current drug overdose epidemic, and many of us who thought we were stamping out needless suffering contributed to the epidemic.

A lot of what I read and believed about opioids early on in my career was wrong.

I’m old enough to remember those heady days in which there was a pretty large and ‘successful’ movement in American medicine to greatly liberalize opioid use for all sorts of pain syndromes...pain as the 5th vital sign, discussions of there being a tort for undertreating pain, etc. In my own way, I was part of the movement, although I was trained at the beginning of the end of the movement.

There was a utopian feeling in the air at the time: pain is a terrible scourge, it’s under-diagnosed and under-treated, it’s this huge cause of all this disability and needless suffering, and liberalizing the availability of opioids would be a key intervention to transform all these suffering people’s lives for the better.

We were wrong.

Opioid prescribing and availability did increase markedly, but population levels of pain and disability didn’t improve. Most people’s lives were not transformed for the better, and at least some were ruined via iatrogenic opioid use disorder. How many were ruined due to increased opioid prescribing for chronic pain is really tough to know. But undoubtedly there was a marked increase in community exposure to prescription opioids (obtained both legally and illegally) from 2000-2010 which was key in fueling the current drug overdose epidemic, and increased prescribing was an important enabler of all this.

And while I very much believe that, I still observe that we actually have very little helpful data about nearly anything to do with this topic, despite the fact that everyone (including me) has strong opinions about it.

Even questions like 'How many patients with chronic noncancer pain who are prescribed opioids also have an opioid use disorder?' has no clear answer (let alone the associated-but-different question of ‘How many patients with chronic noncancer pain who are prescribed opioids acquire an opioid use disorder from those opioids?’). Estimates are from 3-40%, but the data are heterogeneous and difficult to interpret, which is a polite way of saying the data are a total mess. Eg, most studies are single institution studies, some studies have rigorous definitions of OUD, some which look at ‘aberrancy’ which is not an adequate proxy of opioid use disorder, some studies clearly involve a chronic pain population, some which look at anyone who has received an opioid prescriptions which is not the same thing as a chronic pain population – the data are a total, flaming, mess. See, eg, J Med Toxicol 2012 PMC: 3550262, or Subst Abuse Treat Prev Policy 2017 PMID: 28810899).

There are better population-level data on rates of overdoses in patients who are prescribed opioids as outpatients. The big story there is that while risk of overdose does increase more or less linearly with the amount and duration of opioid prescribing, the absolute risk goes from – on a population level – miniscule to tiny as prescription opioid ‘exposure’ goes up. In one of the better studies on this, which looked at state-wide North Carolina data, the risk of fatal overdose was 0.022% per year for all comers (anyone who received an opioid prescription). For those in the highest tier of prescription opioid exposure, the rate of fatal opioid dose remained tiny: 80 per 10,000 person-years (Pain Med 2016 doi:10.1111/pme.12907). That’s still too many, but I think it helps give nuance to the apparent Extreme Urgency some policy makers and insurers are putting on patients/prescribers to rapidly push a whole bunch of people off of chronic opioid therapy. You get a sense that some policy makers think We Must Do This Or They All Will Die. This is totally, demonstrably, false.

It’s illuminating, for instance, to look at Krebs JAMA 2018. This was a 12 month practical randomized controlled trial of opioids in a narrow patient population – osteoarthritis – showing that opioids generally weren’t effective and had opioid side effects. A lot could be said about Krebs 2018, but it was at least a reasonably lengthy study period, and helpfully showed that opioids weren’t generally effective for osteoarthritis in this population over a pretty long time. Although, importantly, the study excluded patients who had received any opioids, so all these patients may have been pre-selected to not do well with/want opioids anyway. Regardless, and relevant to the larger discussion of the opioid crisis, it also importantly showed that while the patients receiving opioids had common opioid side effects, they did not acquire opioid use disorders, nor die at a higher rate than the non-opioid users. So while Krebs 2018 has been used very loudly by some to prove opioids are ineffective for ‘chronic pain’, it’s often missed that it could just as easily be used to emphasize that prescribing opioids carefully to risk-screened patients then monitoring them closely over the long-term is actually quite safe and in fact not a driver of the opioid overdose crisis.

All this being said, opioid prescribing in the US went up massively in the 1990s and 2000s, and I myself don’t have any doubt that lead to broadening the population-level exposure to opioids and fueled the current crisis. All of us who prescribed are implicated in that in some way.




As much as I believe the above to be true, opioid prescribing has been falling since ~2010, as drug overdose deaths have continued to sky-rocket due to a resurgence of heroin and now illegally manufactured fentanyl analogues. And current policies which have essentially forced (encouraged? forcibly encouraged?) clinicians to taper patients off opioids despite many of those patients demonstrating long-term safety with chronic opioid therapy is barbaric, harmful, & shameful, and I’m proud of the efforts of many in our field and organized medicine to push back against it. See for instance Chad Kollas’ (@ChadDKollas, see also his Pallimed posts here and here) and others’ work at AAHPM, the AMA and elsewhere, and the coalition who put together this open letter. Read the letter if you haven’t, it’s clear headed and right about everything, and I’m glad that there are at least signs the CDC is listening, which is not to say that the semi-literate insurance representatives who cannot read a prescription indication line which says: “chronic neoplasm related pain” and who refuse to allow my terminal cancer patients refills without hours of wasted work, are listening…yet.

And, just to wallow in my anger about all this a bit, it’s become really crystal clear to me that there’s a large group of people out there who are enforcing a version of the CDC guidelines that just don’t exist. (In case you’re not familiar with the guidelines: 1) they are aimed at primary care clinicians not pain specialists, and they can be quite easily summarized as saying 2) chronic opioid therapy, particularly high-dose opioid therapy, for chronic noncancer pain should be used rarely, as a last resort, and only undertaken with clear informed consent of the patient and with close attention to the safety of the patient.) Like pain doctors telling their patients who they’ve maintained on chronic opioids for years that the CDC says they can’t do it anymore and have to taper them (I hear this all the time). Or a pain doctor at a peer review of a specialist physician accused of overprescribing stating that the CDC guidelines state that opioids can’t be used for chronic pain (100% true story, I was part of that peer review). Or state policies and insurance plan policies making it nearly impossible to prescribe moderate to high doses, even in circumstances where a patient has demonstrated long-term safety and stability, etc.

But…

While I think forced tapering of stable/thriving patients “because CDC” is wrong and harmful, I’ve found myself in the past 5 – 10 years accepting that many patients on chronic opioid therapy for ‘chronic non-cancer pain’ and even long-term cancer pain, can be tapered and have a better quality of life off opioids, or on lower doses. Some won’t and we can’t tell in advance all the time who will benefit from opioid tapering or not, and it’s really important that those patients whose lives worsen with opioid tapering are cared for by knowledgeable clinicians who can manage their pain including continuing chronic opioid therapy.

All that’s true, but I continue to be impressed with the number of patients who do great with opioid tapering – it’s a lot of effort and, literally, pain on their part, but many feel better afterwards, have a better quality of life, and honestly I would never have believed that 10 years ago and it’s taken me seeing it over and over again to believe it. It’s really changed my views on opioids, and I continue to believe we really don’t know a lot about what opioids do, how they work, how they affect our patients’ perceptions and emotions.

It’s important to be really clear why I think many of these patients should be helped through a tapering process: it’s not because most of them have substance use disorders, it’s not because they are using opioids dangerously or contributing to the larger opioid crisis (these patients are some of the most highly scrutinized patients in all of medicine), it’s not because their risk of overdose is large (there is a risk, but it’s small), but it’s because opioids are not improving their quality of life, and are often worsening it, and they will feel better and be happier off of them. It’s been so eye opening watching many of my patients go through this – talking about how they can feel their emotions again (and all the messiness of that, but they are grateful they have their emotions back), about how reducing opioid doses was painful but after several months they find themselves being more active, they still have pain but it’s manageable, etc. It took me a while to come around to this, but I’ve now seen so many patients whose lives have been markedly improved coming off opioids, that I routinely work with my patients with longer prognoses to reduce their opioid doses, and it goes pretty well most of the time, and like most hard lessons in medicine, I learned it from my patients.

Read the rest of this series:

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph

For more Pallimed posts about opioids.
For more Pallimed posts by Dr Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

Thursday, October 3, 2019 by Drew Rosielle MD ·

A Series of Observations on Opioids By a Palliative Doc Who Prescribes A Lot of Opioids But Also Has Questions.

by Drew Rosielle (@drosielle)

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.

This is the first in a series of several posts about many aspects of my current thinking about opioids, with a focus on how my thinking about opioids has changed over the years.

Opioids, opioids, opioids. The working title of these series of posts was in fact “Goddamned Opioids and the Goddamned Opioid Crisis’ because it’s a confusing time out there. A lot of us in palliative care have watched the unfolding, devastating, opioid overdose crisis in the US with dread and horror, as well as the multitude of responses to it, some of which have been harmful to patients.

But, on the other hand, the reality is my thinking about opioids now, in 2019, is markedly different than it was in 2009. A lot has changed, I’ve changed, and honestly I’m a lot less enthusiastic about opioids’ therapeutic potential for treating pain than I was 10 years ago. I hope to describe those changes and the evolution in my thinking about opioids over the last decade here, and to look at some of the very basic assumptions we make about opioids.

This series of posts is not going to be solely about the overdose crisis and opioid policy. I plan on talking about some of the things I believed early in my career, which I no longer believe to be true – like the preferability of long-acting opioids, opioid equianalgesic tables, opioid ceiling effects, and my thoughts about the current fashion of ‘exempting’ cancer pain and ‘patients receiving palliative care’ from some of the newer guidelines and policies. Hint: I don’t think it’s an unequivocally good thing those groups are carved out.

It should be noted that I know I’m discussing a convoluted and emotional topic, but in order to talk about it one must talk in generalities, so I will talk in generalities. And I just want to say that I will make liberal use of qualifiers like ‘mostly’ or ‘rarely’ and that when I use such qualifiers I am doing it deliberately. Mostly means mostly, not always; rarely means rarely, not never. E.g., if I were to say something like “high dose opioid therapy outside of end-of-life care is rarely helpful,” I in fact mean rarely, and I do not in fact mean never, because I know there are important exceptions, even if I don’t take the time to elaborate all the examples that don’t fit into the generalized statement.

As I’m writing that disclaimer, it strikes me that in fact a lot of what’s wrong with the current policy discussions about opioids is that the at-times-very-well-intentioned policies to restrict access to opioids fundamentally take the tactic of eliminating our ability as clinicians to care for those exceptions (those exceptions being our patients, who are in pain). I.e., a policy takes the fact that post-op opioids are overprescribed (which they absolutely, 100%, are), and the fact that for many surgeries many patients do just fine with, say, 3 days of low dose opioid therapy (also absolutely true), but then policy is created which effectively makes it very difficult for clinicians to adequately treat the minority of patients whose post-op pain course requires higher or longer doses (for example, mandating only 3 days of meds get prescribed post-op, even if they are discharged on a Thursday and if the patient needs more meds on a weekend no one is available who can e-prescribe opioids; or by essentially auditing/scrutinizing/punishing clinicians who prescribe more than than ‘the standard,’ even when it’s completely clinically appropriate and safe, thus discouraging the clinician of appropriately caring for the patient because they are being told from many stakeholders that ‘good care’ is ‘not prescribing a lot of opioids’ instead of the far more nebulous but ‘actual well-being of patients’).

It’s this elimination of our ability to provide individualized care for patients on the rightward end of the long-tail of opioid need that is a major problem so many of us are facing right now.




Read the rest of this series:

Part 1 – Introduction, General Disclaimers, Hand-Wringing, and a Hand-Crafted Graph.
Part 2 – We Were Wrong 20 years Ago, Our Current Response to the Opioid Crisis is Wrong, But We Should Still Be Helping Most of our Long-Term Patients Reduce Their Opioid Doses
Part 3 – Opioids Have Ceiling Effects, High-Doses are Rarely Therapeutic, and Another Hand-Crafted Graph




For more Pallimed posts about opioids.
For more Pallimed posts by Dr Rosielle click here.

Drew Rosielle, MD is a palliative care physician at the University of Minnesota Health in Minnesota. He founded Pallimed in 2005. You can occasionally find him on Twitter at @drosielle.

by Drew Rosielle MD ·

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