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Buprenorphine.  It’s been around for a long time but is acting like the hot new kid in town.  Just look at this year’s AAHPM meeting, where it felt like every other session was talking about how hot buprenorphine is right now.  But does this drug really live up to the hype?

On today’s podcast we talk with three experts on buprenorphine on why, when, and how to use it in serious illness. Our experts include Katie Fitzgerald Jones (palliative nurse practitioner and doctoral student at Boston College), Zachary Sager (palliative care physician at the Boston VA and Dana-Farber Cancer Institute), and Janet Ho (physician at UCSF in addiction medicine and palliative care).

We try to cover a lot in a 45 minute podcast, but if there is one take-away, it’s that all of us who prescribe opioids should learn how to use buprenorphine and that we should all sign up for a DEA X-waiver at or at (now you can treat up to 30 patients without completing the additional educational training, so signing up takes about 5 minutes). 

And if you want to learn more about buprenorphine from these amazing palliative care clinicians and others, check out of some of these articles:

Learn more about caring for those with substance use disorder: 

Learn about using the low dose buprenorphine patch: 

Learn about how to initiate buprenorphine: 

Good review on buprenorphine for pain

Two great videos on buprenorphine initiation

Article on buprenorphine in the elderly

Eric: Welcome to the GeriPal Podcast. This is Eric Widera.

Alex: This is Alex Smith.

Eric: And Alex, I am very excited for this podcast. We got some really special guests with us. We’re going to be talking about buprenorphine, lots of fun stuff. This was the hot topic at AHPM. Alex, who do we have with us today?

Alex: So we have Katie Fitzgerald Jones. Who’s a palliative care nurse practitioner and PhD candidate at Boston College. Welcome to the GeriPal Podcast, Katie.

Katie: Thank you. If I was a emoji right now, I’d be the Jonah Hill with his hands this screaming I want to be here. [laughter]

Eric: That’s great.

Alex: We have Zach Sager. Who’s a palliative care doc and psychiatrist at the Dana Farber in VA Boston. Zach, welcome to the GeriPal Podcast.

Zachary: Thanks for having me and really excited to talk about this.

Alex: And we have Janet Ho who’s a palliative care clinician and attending physician at UCSF on the palliative care service and addiction medicine. Welcome to the GeriPal Podcast, Janet.

Janet: Thank you. Thank you guys so much for having us here.

Eric: So I listened to three different talks AHPM annual meeting about buprenorphine including the precon. I think during that time at the very end, Katie, mentioned about being on the GeriPal Podcast and also already having a song request if I remembered correctly. Katie, before we jump into the topic of buprenorphine in serious illness, what’s the song request?

Katie: I have to thank Rachelle Bernacki for this because she told me the secret to getting on the GeriPal Podcast is having a good song. So I have thought about this for months, maybe years since your 2016, cycle blog, but we have picked Under Pressure by David Bowie and Queen.

Eric: And why Under Pressure.

Katie: Because I think it reflects this tipping point in our field around opioid complexity and leaning into caring for people with serious illness that have concurrent opioid misuse or use disorder. And I also love the message at the end about can we give love because a lot that speaks to the work that we’re doing in harm reduction which is really meeting people where they are, loving them, where they are, and then not just leaving them there.

Eric: That’s a great message.

Alex: That is great. So for those of you listening via YouTube, here’s the live version for those of you who are listening on the podcast, you’re going to get my prerecorded version with lots of loops and I’m doing consultation with my new music teacher who’s a music producer in LA.

Alex: So we’ll see what these come out like. So here we go. A little bit of under pressure.

Alex: (singing).

Eric: Good job. At the end, you’re going to do the whole Vanilla Ice song. Right? Alex.

Katie: But it’s slightly different.

Eric: That’s what Vanilla Ice did – that’s how we try to get out of the lawsuit, right [laughter]

Katie: I know. Remind of that MTV thing.

Eric: Thank you, Alex. I’d to start off just briefly talking with each of you. How did you get interested in this topic of buprenorphine and serious illness? I’m going to start off with Katie. This is both a research and a clinical interest of yours. Right, Katie?

Katie: Yeah. Exactly. I mean, I think where it started for me was that I’ve been in palliative care for a long time as evidenced by my dedication to your podcast. But I was struck by caring for people with addiction that they had suffering that we just entirely ignored. They were die anyway sort of mentality.

Katie: So just give them what they want. Don’t worry about their alcohol use or drug use. Give some pleasure. But that just didn’t really resonate with what I saw clinically which was that there was lots of suffering both in the patient, their family and on the clinical team and just felt it was really this space where I didn’t have a lot of evidence to guide me.

Katie: And also quite honestly I wasn’t feeling I was very good at it. I think Zach and I talk of stories about times where we’re really messed up and haven’t gotten it right. And so I think that drove me to research too to feel if I had more empiric data to better understand how to best support people, I could then champion others to be better at it. And along the way I have since improved.

Eric: I mean, there was some old mantras in palliative care, if you’re treating pain, you won’t get addicted to it that were clearly not rooted in the best evidence. Zach, how about you how did you get interested in this?

Zachary: I mean, I did my med school and residency training in Louisville, Kentucky, and I had a second year med student lecture from Joe Rotella who was, I think the chief medical officer at Hospices at the time. And we had a required palliative care rotation as a third year medical student and I really loved palliative care and was like I’m going to do this but I couldn’t figure out what I was going to do before that to get to that.

Zachary: And psychiatry kind of felt the thing that resonated. And during residency… I mean, this was also in Kentucky, right at this intersection of Ohio, Indiana, Kentucky, West Virginia. And I was seeing patients that were coming from Eastern Kentucky for addiction treatment, seeing patients that were coming out of these pill mills and just cared for a tremendous number of people who had opioid use disorder or opioid addiction.

Zachary: And with just wondering I’m going to do palliative care, I’m going to take care of folks with pain but I’m seeing these patients now and what’s going to happen when they develop cancers or serious illnesses in 10, 15, 20 years. And how am I going to manage their pain?

Zachary: And so that was really kind of the impetus for figuring out, how do I figure out this intersection of substance use and pain because it didn’t feel anyone was really doing it well and it was just you make it up as you go along.

Eric: And Janet, you actually did a fellowship in addiction medicine, right?

Janet: That’s right. So I mean exactly in line with what Katie and Zach said, I think it started out with just having the sheer luck of having gone to residency at Yale where there’s a cadre of attendings for whom being able to treat opioid use disorder and consequences of long term opioid use was just as important as knowing how to prescribe opioids kind of responsibly.

Janet: And so that was my first taste of kind of addiction medicine. And it really sticks with you I think but Katie, Zach and I talk about just, if you could see a patient being treated for opioid disorder and doing well, it’s pretty life changing both for that patient and for yourself as a provider.

Janet: But subsequently I went to MJ for fellowship and palliative care which I knew I wanted to do. And I remember being there and there was a patient who had seen inpatient and then subsequently outpatient who was so thankful in the weirdest in just this irrational way for having been diagnosed with liver cancer.

Janet: It was this young man. He was in his mid twenties. And he was so thankful that he kind of ended up in the hepatic coma and got diagnosed with liver cancer because it was his chance to be linked to treatment for addiction, which is so extreme. And it’s so kind of backwards when we know that there’s really strong evidence for the different treatments that we have for addiction that people just don’t have access to.

Janet: And so that kind of helped me think as a fellow that we should be able to offer this regardless of what type of clinician we are. That it’s our responsibility, especially as opioid prescribers. And then part of our role as folks in palliative care who as Katie mentioned, really try to help folks manage distress around serious illness.

Janet: And so all of those things motivated me to just learn as much as I can about treating addiction. And then now in thinking about it with colleagues who work kind of in the two areas is how do we take that addiction, medicine, knowledge, and workflow, and adapt it to caring for patients with serious illness because it’s not as simple as just transposing what they do in addiction medicine onto caring for patients with painful serious illness.

Eric: What is the role for people caring for those with serious illness? They’re not addiction medicine specialists. They don’t have an addiction clinic. It’s not staffed that way. What is the role for those who are caring for seriously ill patients to know about addiction medicine and to care for these folks?

Janet: Oh, absolutely. That’s a great question. And I think that we would kind of enthusiastically say that it is definitely part of our role as palliative care clinicians to have a certain level of primary addiction, medicine, knowledge and competence.

Janet: So as Julie Childers often says in the same way that as palliative care clinicians we can take a first pass to address distress from depression without being necessarily mental health counseling specialists or a psychiatrist.

Janet: We should have that same level of familiarity and comfort in approaching, assessing, and offering treatment to somebody who has a substance use disorder. And then knowing when to kind of reach out for co-management or when to reach out to specialists for higher level care.

Zachary: We do lots of really tough stuff in palliative care. And I often think about in the scheme of hard things we do in palliative care, we’re thinking about managing patients in the ICU and using ketamine and methadone rotations. Identifying an opioid use disorder and starting buprenorphine is not in the same ballpark as that. And I think once you have some basic skills it feels very within one’s wheelhouse if you’re willing to kind of make that step.

Eric: My thought too is that there is this especially for palliative care clinics where we’re going farther and farther uphill, what defines a serious illness. If somebody’s dealing with a chronic pain and multiple chronic diseases, they have an opioid use disorder and we get referred that patient to a palliative care clinic is that in our Bailey wick? Is that something we’re doing? Are we mainly thinking about in people with advanced cancers?

Eric: And I think this is one of the things that I struggle with the most is who is as we move closer, farther and farther away from immediately dying patients who are the right patients to serve in palliative care clinic and who are the ones that we should also just make sure that they’re getting right places to or for pain clinic or addiction clinic thoughts on that, Katie?

Katie: Well, well first I wanted to underscore something that both Janet and Zach said, which is that this isn’t hard and people get better. That’s the part that really I struggle with a lot is I feel in our field, there’s this therapeutic nihilism and that people with opioid use disorder don’t get better. There was that New England Journal paper, harder to treat than leukemia. There was addiction as a terminal illness.

Katie: And there’s this idea that you’re stuck with somebody with this untreatable condition but prescribing buprenorphine alone improves mortality. So I think also just to say, you don’t have to be an expert. You don’t have to be perfect. You just have to connect with people and be able to meet their needs.

Katie: And I would say in response to your question, Eric, that I think for a lot of patients deciding if they our patient population, we often take a first pass and say, I might not be the person that can manage you for the next five years with your COPD.

Katie: But let’s just see how things are going. What’s causing you suffering right now. And if it’s an opioid use disorder start treatment and then transition them out of your clinic. And that’s a lot easier if all providers were X waivered too.

Katie: So I think one of the challenges is that the way that the climate is right now is that palliative care is becoming the default practice for opioid prescribing in general. Nobody wants to prescribe opioids anymore, which is a problem. And I think if we advocate for opioid access, we should also be advocating for addiction access.

Katie: So there’s no clear demarcation about who falls into serious illness care. I think Diane Meyer says whoever wants it.

Eric: And then let’s talk about treatment. We’ve mentioned buprenorphine, is that kind of the main thing that we should be thinking about in palliative care clinics and geriatric clinics for people with your use disorder?

Zachary: I think it’s important. I want to jump back just to highlight kind of who the patients are because I think when we are in palliative care, I’m mostly in a palliative care clinic setting, both in the VA and then at Dana-Farber.

Zachary: So seeing a non-onc population at the VA and out-patient at Dana-Farber, and that when someone comes to me with a diagnosis of opioid use disorder, it is much easier you kind of have an idea of where you’re going to start. The patient has some shared understanding of what the issues are.

Zachary: And so it’s really much more straightforward to collaborate with them about thinking about how you’re going to manage their pain and their suffering. I think where we are in where the kind of bigger pot of patients we care for in palliative care is patients who maybe meet the opioid use disorder diagnosis that sometimes or have aspects of it that seem they align with opioid use disorder but other parts that don’t.

Zachary: So it’s kind of this middle ground patient population that we wind up caring for and identifying an opioid use disorder maybe over time. But it takes sometimes multiple visits months or longer sometimes to be able to first identify actually what’s going on.

Zachary: And then I think in that then buprenorphine becomes a really important tool that we can use as palliative care providers because some of the other addiction treatments are just not going to work for our patient population.

Eric: And are there any good assessments for opioid use disorder that our listeners could use?

Janet: There are but just to kind of piggyback off kind of what Katie and Zach are saying back to your question of I think as palliative care grows it heads upstream on the one end. And as it is extended on the other end with all these disease directed therapies and people are living longer, that gray area where we know that people who have serious illness and get touched by palliative care tend to end up on opioids.

Janet: And tend to end up on opioids for long time winds itself to added clinician distress with what to do with those opioids especially concerning behaviors or concerning use of opioids that might arise. And buprenorphine is this great tool that’s underutilized that can help both the clinician with that distress and with the patient.

Janet: So for instance should it be used as a first line kind of analgesic for somebody especially when they come in and they’re really young? Should it be used more often on the tail end as people are survivors of cancer to minimize kind of the harms from exposure to full agonist? And then how do we use it kind of in between for people who are in this gray area of either some opioid misuse or some concerning use or with frank opioid use disorder?

Janet: I think that’s the beauty of buprenorphine is that it really lends itself to all of these different places as our patient pool grows.

Eric: So let’s talk about buprenorphine but before we do just want to say, is there a good assessment that we could do for opioid use disorder?

Katie: I think to Janet highlighted a couple which is typically we use the four Cs which is use despite consequences, loss of control, cravings, and compulsive use. So those are sort of the acronym to remember. But I also think to what Janet and Zach said, a lot of our patients kind of fall into this gray area. Some people call it complex persistent opioid dependence, which is sort of they’re on opioids, it’s not going well. They have poor pain, they have poor function, but you also can’t clearly make a diagnosis.

Katie: And for those patients that’s when your gut is telling you, it’s ill advised to continue full agonist. And in that case, buprenorphine is really helpful. And sometimes you can make a use disorder of diagnosis in hindsight. It really becomes clear all the things that we’re causing chaos and problems sort of dissolve as you use buprenorphine in the craving stop.

Eric: So let’s talk about buprenorphine. So Janet, what is buprenorphine? You said it’s not an agonist. What is it?

Janet: So buprenorphine is mu opioid partial agonist or it’s a partial agonist at the mu opioid receptor. And so that lends it properties of being a pretty strong analgesic and it lends its special properties for safety, from a safety profile.

Janet: And so being a part partial agonist, it just means that there’s a certain threshold where beyond that, if you continue to increase the buprenorphine, you will hit a ceiling or a limit to adverse effects at the mu opioid receptor such as respiratory depression, such as potentially constipation, such as kind of cognitive impacts.

Janet: And then excitingly for buprenorphine, it also has some action at other opioid receptors. So it’s Delta or it’s capa receptor and agonist which is thought to reduce its effects on kind of euphoria and cravings with opioids and also to help reduce things like depression and hyperalgesia.

Janet: And so those are kind of some unique properties for buprenorphine that we don’t quite have with our other full agonists.

Alex: I feel I’m going to do better on my boards now. Great. Wait. Let me just summarize to make sure I get it for our listeners. Because this is pretty key. It’s a new agonist and a capa antagonist.

Janet: That’s right. Specifically it’s a very high of affinity. Mu opioid receptor partial agonist.

Alex: Partial agonist which means that there’s a ceiling effect as far as side effects that you normally see with opioids. And then it also doesn’t cause the same degree of euphoria that opioid would cause.

Janet: I think there are some studies to examine whether it can help kind of with mood and depression as well.

Alex: Is it an opioid…?

Janet: It is an opioid.

Alex: It is. Okay.

Janet: So at the end of the day, it’s a pretty potent opioid. And I think the natural next question is when you hear a partial agonist and ceiling effect because people wonder whether that translates to pain and analgesia. And I’ll just say that from what we know from both animal studies as well as human studies, in patients who are postop from GI procedure and women who’ve are post C-section. That it’s a pretty effective opioid analgesic.

Janet: And so there’s no evidence thus far that there is a ceiling effect on the analgesic properties of buprenorphine. That said, I think there might be some anecdotal reports of how effective it can be for somebody with rapidly escalating pain, for example, terminal pain or with rapidly progressing disease. But for the most part, I think for most of our uses, we should consider it no less than any other opioid.

Alex: Thank you.

Eric: And good go to that last point too. So one of the older school mantras was that with a partial high affinity, partial agonist, if we’re admitting somebody to hospice, we think their pain is going to get worse, that it actually may be harder to treat their pain with other short acting opioids if they’re on a partial agonist as high affinity for those mu opioids.

Eric: So buprenorphine immediate release oxy or morphine may not work as well if they’re on a patch of buprenorphine. Is that true? Seems it’s tricky.

Zachary: I think there’s one important part is that there’s a ton of formulations of buprenorphine. And so I see this clinically, I have someone who is on a five microgram buprenorphine patch, which is a really low dose intended for people who are otherwise opioid naive.

Zachary: And that’s really different from someone who’s in addiction treatment and is on 24 milligrams of sublingual buprenorphine. And so they’re adding a full agonist to both those patients is going to look different but I think most people see buprenorphine and they think like, oh, this is an opioid blocker. They’re not going to get good treatment or good effect with a regular opioid which is not true.

Zachary: So I think a lot of the time we’re fighting which formulation someone’s on and for particularly on patients on hospice sometimes they stay on I’ve had patients on hospice who have stayed on buprenorphine until the very end of their life. And it works fine.

Zachary: Sometimes we make the decision that we that the buprenorphine is no longer indicated and can switch to a full agonist and they do well with just a regular starting dose of a full agonist. Or sometimes we wind up kind of layering on a full agonist and then that dose gets fairly high and we take off the buprenorphine.

Zachary: So there’s not one pathway to that for folks on buprenorphine. And I think that’s one of the things that makes it awesome that it comes in all these different formulations with all these different indications but also the thing that makes it really-

Eric: It’s scary.

Zachary: Yeah. Scary or a tricky thing for folks to navigate especially when they’re starting out.

Eric: In general, that you have whether or not it’s given through a patch or via other routes and also whether or not it’s given with Naloxone or not. Right?

Katie: Well, I want to just make a strong point that the patch is never going to block anything because it’s just so small. Somebody could be on the highest dose patch and it wouldn’t block anything. It’s micrograms compared to milligrams doses of Suboxone. And so I do think it’s really important just to say that. What was the other-

Eric: And that’s the Butrans patch, is that right?

Katie: The Butrans patch.

Eric: What doses are we usually starting people in?

Katie: Five and then it can go to 10, 15, 20. And in Europe they use higher doses than 20 but 20 is the highest we got.

Alex: Can I clarify what you mean there by it’s not going to block anything. What do you mean specifically by anything?

Katie: I mean, I think there is this idea that buprenorphine blocks the effect of other opioids. And again, I think as Janet was alluding to think that’s an area of unsettled science. I think that we… For example, in the postoperative literature, people that remain on their buprenorphine for opioid use disorder use less opioids and have better pain control when their buprenorphine is continued.

Katie: So I think that a similar to what Eric was describing 10 years ago, I was stopping buprenorphine and adding a full agonist because I was worried or I was using high doses of full agonist because I thought maybe buprenorphine was impacting its efficacy but that’s not what we see in the literature.

Alex: So what you’re saying is it’s not going to block the analgesic properties if you add another opioid on top of the buprenorphine patch.

Katie: Correct.

Eric: So let me ask you this-

Alex: Will it still act at the capa antagonist to block the feelings of euphoria associated with the additional opioid you give your patient?

Katie: I don’t think we would see… I think the evidence for the capa, you can correct me if I’m wrong, Janet, but this is normally with higher doses with Suboxone.

Janet: So I think as everyone’s pointing out. Part of the tricky nature of buprenorphine is that it’s used in so many different ways for so many different indications. And I think what’s helpful to know as a palliative care clinician is that we have maybe what we consider lower dose formulations of buprenorphine which include the patch which comes in the lowest dose.

Eric: Those are micrograms per hour. We’re talking about five micrograms per hour.

Katie: Right. Which some people might consider even just a homeopathic dose but for someone who’s naive that might be where you start. And so it goes from five to 20 or even with two patches up to 40.

Katie: And then on the lower end of the dosing still is the buckle formulation of buprenorphine which is also FDA approved for pain just like the patch is. And so the buckle kind of crosses over from this low dose where the patch ends to a slightly higher dose.

Katie: And then what we consider moderate to high dose would be the sublingual version. So those might be the formulations that come with the Naloxone as the combination product or they are also available as the mono product. And those tend to start at the two milligram dosing level and then can go up to 24 or 32 milligrams a day.

Katie: And I think what Zach was saying is that the level of this hypothetical blockade of the opioid receptors by this high affinity buprenorphine really varies whether you’re on this low end patch or buckle formulation versus if you’re at 24 32 milligrams of sublingual buprenorphine a day.

Katie: And so as additional context that I found helpful when we treat addiction we aim for somewhere between 16 to 24 milligrams of buprenorphine a day to help block cravings and to help maintain stability.

Katie: And for patients with pain or chronic pain, you might get an effect a really good analgesic effect at much lower doses. So it might be with a patch that’s 20 micrograms day or it might be on four to six milligrams of sublingual buprenorphine instead of at the 24 to 32.

Eric: It reminds me of methadone where lower doses can be effective for pain and much higher doses are used to treat-

Katie: Absolutely.

Zachary: And I think it’s helpful to kind of think about because there’s other formulations that are not used by palliative care that I will sometimes have an image of a composite patient for each of the indications.

Zachary: And so for my composite of a patient who comes to me in palliative care clinic, who would end up on a low dose transdermal buprenorphine would be an older patient who’s maybe had a poor experience with 2.5 or five of oxycodone or comes to me and says they’ve had a history of not tolerating other opioids.

Katie: Right. They’re asleep for a week after five of oxycodone.

Zachary: Yeah. Or someone who really doesn’t want to take medicine but has chronic pain, Tylenol and ibuprofen’s not cutting it. And so that would be the patient who I would think, okay, this person, I’m going to start at five of transdural buprenorphine and they’re going to end up somewhere in this five, 10, maybe 15 microgram range.

Katie: In fact also that it would be ideal for an older adult because it’s every seven days and they don’t have to remember to take it. If, for example, they have cognitive impairment.

Zachary: Exactly.

Eric: Five would be kind of your starting dose of buprenorphine. Let me ask you another question real quickly. So imagine that same patient, Zach, but they’re already on opioids. Do you have to worry at all at those very lower doses? Are they going to detox from their or opioids if you put them on?

Zachary: No, it’s a great question. I used to stress about that even though when I knew they wouldn’t. They wouldn’t have it. I remember the first couple patients who I would rotate from a full agonist over to a transdermal buprenorphine product because they just weren’t tolerating full agonist. I’d be talking with Katie or Janet. And so just checking if this was okay.

Zachary: So no, I mean, we know because the dose is low and we also use that, in other words, we use the patch as a way to also kind of get people onto a higher dose form because it’s a slow onset.

Zachary: And so the general thumb is if you’re opioid naive or maybe taking one Tramadol every three days or a really low dose of oxycodone that’s not cutting it every few days that person’s going to start on five micrograms.

Zachary: If someone’s on a low dose of a full agonist maybe a total of 5, 15, 20 OMEs a day, they’re going to start on 10 milligrams or 10 micrograms, sorry of the patch. And then for patients who on a little bit higher, I might start a little bit higher on the patch but often I’ll still start on the 10 microgram patch.

Zachary: And I would generally say if someone’s on a full agonist put on the patch, take your normal opioid dose, see how you feel an eight, 12 hours. If you need to take another breakthrough dose, if you’re old, full agonist, do that. And then after about 1224 hours, you’ll kind of get a sense of if this dose is going to be effective or not.

Zachary: And I would say most patients who have that have transitioned from a low dose of a full agonist onto transdermal buprenorphine find that, and it didn’t really do anything for the first eight, 12 hours, which makes sense because it’s a transdermal product.

Zachary: But then after about 12 hours or a day or a day and a half then they’re kind of noticing that it’s kicking in and then they’re taking less of their full agonist. And eventually if the goal is they eventually stop.

Zachary: So five naive, 10, if they have a little bit of opioids in their system’s kind of how I will teach it.

Katie: And it does take 72 hours to reach study state but fentanyl I think that we see people have it kick in a little bit earlier than that but it won’t precipitate withdrawal.

Janet: I think that’s really the question that you’re asking. Alluding to is that perhaps in many of our clinical training, we’ve come across some amount of buprenorphine training and kind of the take home is always watch out for precipitated withdrawal. If someone’s on a full opioid agonist and you add buprenorphine because it’s a high affinity opioid it’s going to kind of displace or outcompete the full agonist.

Janet: And then because it’s a partial agonist, it might exert only part of the opioid effect that the person was on getting before. And that Delta, that shift in opioid load is going to feel precipitated withdrawal.

Janet: And because of that phenomenon, a lot of the initiation for especially higher dose buprenorphine starts with people stopping their full agonist, entering kind of withdrawal and then getting rescued from that when you give them buprenorphine.

Janet: But what Zach and Katie are referring to is this newer method it’s called low dose initiation or you might see it called microdosing wherein you just introduce tiny, tiny amounts of buprenorphine separated by enough time, such that it slowly, slowly builds up and doesn’t cause that rapid shift.

Janet: And so you end up kind of with the staggered cross taper where you introduce little bits of buprenorphine up to a certain threshold and then you can take off the full agonist and then continue to titrate up the buprenorphine with really minimal risk of causing precipitated withdrawal.

Janet: And so one of the methods that’s kind of the most patient friendly for doing this is actually using that buprenorphine patch…

Eric: Do you need an X waiver for a buprenorphine patch?

Janet: I do not.

Zachary: I do not.

Eric: Why is that? Why do some formulations you need X waiver and some you don’t?

Zachary: Racism. [laughter]

Katie: Stigma

Janet: Stigma. Great question.

Katie: I think this is really the call to action that we hope to make from this podcast is that these policies are not evidence-based at all. This delineation of you can use the same medication for one indication without training. And another indication you need training is just it’s really just steeped in stigma and racist drug policies.

Katie: And we believe that anyone prescribing opioids should have their X waiver because as we’re describing, it’s not as simple. It’s not so simple as saying this person clearly has an opioid use disorder. This person clearly has pain. That is a false dichotomy. You can have pain and addiction and most people with addiction have chronic pain.

Zachary: It’s it using buprenorphine is much easier. I think the challenging is kind of feeling confident enough to start the medication and making the diagnosis. I think again, gathering the evidence in order to identify kind of, okay, this is what I think is going on and then have the patient buy in to say like, I really think that this is the problem. The use of this substance in conjunction with pain.

Zachary: And so I think we’re going to shift how we’re thinking about treating it to use this product. If that what the decision is. I think that is the much harder part than just the kind of pharmacokinetics of or figuring out how to use buprenorphine.

Janet: And just to highlight that when we are able to offer buprenorphine as treatment for opioid use disorder or for somebody who’s having concerning opioid use we’re fitting into this larger social movement of harm reduction which Katie had mentioned in the beginning which is really meeting a patient where they’re at and giving them the tools and empowering them to improve how they can take care of their health.

Janet: And so this is one way that as palliative care clinicians we can proactively fight against this whole legacy of really discriminatory and racist policy within the U.S. towards addiction, towards people who use drugs and then even towards the medications that we can use to treat this right.

Janet: And so we have this whole spectrum of buprenorphine at these different doses that we should be able to utilize but people can feel limited just because of this X waiver policy to not fully access and be able to offer all of the medications. And there’s no excuse for that now because as of this year, it is simple to get the X waiver.

Eric: How do you get an X waiver?

Janet: I’m glad you asked because it’s an eight minute process instead of an eight hour process. Super-

Eric: Oh.

Janet: Yes. All you have to do is sign up one click. So you go to the website, the SAMHSA website, and you fill in-

Katie: You can even just go to and it will bring you right there and show you a video

Eric: Oh,

Katie: That moves your mouse for you.

Janet: Awesome. We literally answer some demographic questions of who you are and then it gets sent in and then they’ll send you your ex waiver kind of number 30 to 40 days later. And you don’t have to be limited by these arbitrary policies anymore.

Katie: The waving of the education requirement is for physicians, nurse practitioner and PAs, but in some states, nurse practitioners require their physician to be wavered if they or live in a reduced or restricted scope of practice. So more argument for team-based care.

Eric: And then if somebody wants to learn more about buprenorphine and serious illness details getting to dosing different types, is there a good review article that we should turn our listeners to?

Katie: I mean, all of our papers.

Eric: Great. Can we have links to some of your papers?

Katie: Well, we have a FastFax now for the traditional method of buprenorphine initiation. Again, I think there’s sort of some of this is Zach was describing is around philosophy. How can I best care for people at the intersection of serious illness and pain and opioid misuse use disorder.

Katie: And so we have another paper on that. And then in terms of just practically how to use buprenorphine, again, I think I would get your feet wet in terms of both trying it for pain and opioid use disorder because when you use it for all of the indications, you just get more comfortable with the products in general.

Janet: And Katie has a great CAPC blog too that kind of summarizes a lot of additional evidence and references online if you have access to that too.

Eric: And we will have links to that. I got one more lightning question, Janet, you’re at UCSF you’re caring for a patient in the hospital. Who’s, let’s say I’m buprenorphine. And do you think anything differently about how to manage acute pain in those patients? Do you think anything different about how to what immediate release medication you’re going to use to if their pain is, let’s say, getting worse from metastatic cancer?

Janet: Great question. I think it goes back to kind of what Zach was saying is what dose are they on? So if they’re on a higher dose 16 to 24 milligrams of sublingual buprenorphine.

Eric: Instead of a five microgram per hour patch. Five you’re basically saying, ain’t doing anything. Right?

Janet: If someone is on a patch yeah, exactly. Even up to 20, I would approach treatment the way that you normally would. If somebody’s on higher, 16 to 24 sublingual, I might use a breakthrough opioid at a higher frequency or at a dose than I would normally start.

Eric: Would you use one that potentially has a higher affinity to the mu opioid receptor?

Janet: Yeah, absolutely. And so if I’m able to, I mean, in inpatient setting, IV hydromorphone tends to have a higher affinity. Fentanyl has a higher affinity. That said, if we’re in the outpatient setting or if that’s not available, you can get the same GIC effect. With morphine and oxycodone, you just need higher doses or maybe a higher frequency of treatment.

Zachary: And I might also just ask the patient in your history of receiving opioids when you have had pain, which is the medication that seems to work the best for you? And use that as a starting place.

Zachary: You can also inquire with them has there been a medication that has been either triggering for you in terms of thinking about your past use or is there one that you really is important for you to stay away from? If we’re talking about someone who’s on a buprenorphine product because of an opioid use disorder and not a kind of a chronic pain.

Janet: Absolutely.

Katie: I think a mistake would be to stop the buprenorphine. If they were on buprenorphine for an opioid use disorder, don’t stop it. You wouldn’t stop somebody’s insulin. It’s just really important to keep it. And I think Zach and I have frequently shared patients and we have had really challenges where the buprenorphine was stopped and it’s hard to get people back on it for various reasons.

Katie: But really continuing that life saving medication. And if you need to reduce the dose you can but in a lot of instances you might not even have to. And just remember that Naloxone part of the buprenorphine/Naloxone isn’t doing anything unless the person injected it.

Zachary: So especially in the kind of perioperative period, I think before kind of the current of evidence that was available people would kind of routinely stop the buprenorphine because of these worries about blocked receptors. But now we know and even here at UCSF kind of the periop guidelines continue the buprenorphine for stability, reduce it on the day of the procedure, if necessary, just to allow for theoretical more full agonist to work and then kind of up titrate the bup as people recover.

Eric: Well, I also just want to say one more last thing about buprenorphine and I know we’re out of time, but one of my favorite dementia articles was a stepwise pain protocol for individuals with dementia. And it started off with Tylenol then it went to low dose morphine. And the third step was transdermal buprenorphine at 10 micrograms.

Eric: And that pain protocol significantly reduced behavioral issues in dementia nursing home patients. I always thought this article came out 2011. So this is 2008 when they were running this study, I’m like why did the heck did they choose buprenorphine? Nobody uses buprenorphine. And now I think, oh my God, buprenorphine, we should be using more buprenorphine. That’s perfect for this setting in this population. Does that seem right?

Katie: Absolutely.

Janet: Absolutely.

Zachary: Absolutely.

Janet: It’s an old medication.

Zachary: I mean, it was developed in mid 1960s. It started being used for addiction treatment in the seventies at the addiction research center in Lexington, Kentucky. So it’s been around for ages we’re not… I mean, this is new to palliative care and kind of relatively new to a lot of medicine but this is an old drug.

Alex: Is it inexpensive?

Zachary: It should be.

Janet: Depends on the formulation.

Eric: What about Transdermal?

Katie: The Transdermals not cheap because I often have to get a… I mean, I’m at the VA, so I’m spoiled, but you often have to get a prior authorization but for opioid use disorder, since the Affordable Care Act it’s automatically covered. So buprenorphine and Naloxone is covered by law.

Zachary: I would say that shifting from… I used to prescribe solely in the VA and the Shangrila that is the VA and then never had to worry about it and then shifting to outpatient at a cancer center and having to go through commercial insurance. I often need a prior off but I have been surprised that the insurance hasn’t been the barrier that I thought it would be.

Zachary: Sometimes there are other barriers like the local pharmacy doesn’t have it in stock or there’s some confusion about the indication. So sometimes there’s other additional barriers but that I haven’t found at least in the patient population that I’m serving at Dana-Farber that cost of the patch hasn’t been a major barrier to using it which has been good.

Eric: But maybe some other things that put you under pressure.

Katie: Well, I do want to say if a related point if that person with dementia maxed out at a 20 microgram patch that you can use the buprenorphine Naloxone product off label for chronic pain and this is done all the time in the general population. And again those doses equivalents are so different but I would normally start some on half a film twice a day for chronic pain if they were tolerant or two milligrams.

Katie: So the doses aren’t going to be quite as high as that 16 milligram typically for opioid use disorder but that you can go up. So don’t sort of stop just because the indication for the patch stops at 20.

Zachary: And the FDA approval for patch is 20 microgram but in Europe they use up to a 70 microgram patch. And the reason that 20 is the highest is because of a concern for QT prolongation. So there’s not something magical that happens by your QT when you across the Atlantic.

Zachary: So I have had this success in the VA and then outside the VA basically saying petitioning to go above the FDA approved limit. Because I think that concern around QT prolong issues is not really a clinically significant one especially when we’ve got patients on all sorts of other QT prolonging stuff.

Katie: I do remember if you do not cross the Atlantic but cross the threshold of over two milligrams of buprenorphine that’s when you have to worry about adding it to a full agonist in precipitating withdrawal. So you can add full agonist to buprenorphine but you can’t do the opposite order.

Zachary: With higher doses.

Eric: And is there any opioid equal analgesic if somebody’s on a buprenorphine dose, you want to figure out what is a good Dilaudid for them?

Katie: I mean, my hot take is those equal analgesic tables are trash.

Eric: We have podcast coming up with equal analgesic tables.

Katie: Then there’s a great Pallimed blog about it recently.

Alex: That’s why we invited Drew to the podcast.

Zachary: I’ll just say a plug for some of these old studies are great. So there’s these old Jasinski studies that were done at the Addiction Research Center in Lexington, Kentucky. So those that they were studying the use of buprenorphine and they were giving patients who were incarcerated with opioid use disorder, giving them buprenorphine to see if would work.

Zachary: And they those were the studies where they really started to develop the kind of equal analgesic dose or what was the dose of buprenorphine that would block morphine which is not our patient population. And so some of these numbers have been carried forward and copied over a decade.

Eric: So ignore them.

Zachary: In my way, I always tell just ignore the tables. The equal analgetic tables for buprenorphine into a full agonist is going to get you in trouble or going to confuse you. Just ignore them.

Eric: Got it.

Katie: It can just fascinating. You can have somebody on 400 of morphine MMEs and they’re the best they’ve ever been on six milligrams of bup. It doesn’t make any sense. So just titrate it to the patient.

Eric: I could talk for another three hours on this. I really want to thank all of you here. I know Alex has to run, so I’m putting him under pressure. So I’m going to try that again. Alex, do you want to give us more Under Pressure. A little bit more.

Alex: (singing).

Alex: That was a very high song. Thank you for that, Katie. [laughter]

Janet: That was awesome.

Eric: Well, I really want to thank you guys. Zach, Janet and Katie for being on this podcast. I think that was absolutely fabulous. I think we’re going to have you on again because I could talk a for another couple hours about this subject but a very, very big thing. Thank you.

Janet: Awesome. Thank you guys.

Eric: And it sounds if there’s one request for our listeners, for those clinicians, it’s get an X waiver. Right?

Janet: Absolutely.

Eric: Wait, what is the website?



Eric: Encourage all our listeners to go there and we’ll have of links to some more papers by this group on our GeriPal website. And with that, we’d to thank all of our listeners and Archstone Foundation for your continued support.

Alex: Bye everyone.

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