Bobby Mukkamala, MD: Welcome to the American Medical Association Physician Education Podcast on the Opioid Overdose Epidemic. Through expert discussions and insights, this podcast will feature information that can help physicians of all specialties address the epidemic of opioid overdoses. Free CME is available.
I'm Dr Bobby Mukkamala, board certified otolaryngologist and a member of the American Medical Association's Board of Trustees. I also have the privilege of chairing the AMA Task Force on Substance Use and Pain Care. Opioid treatment can change a patient's life by alleviating pain, optimizing function, and improving their quality of life.
However, many biopsychosocial factors contribute to opioid use developing into a chronic use disorder. In this episode, we'll discuss medications for opioid use disorder, acronym MOUD, as well as opioid use disorder treatment considerations and standards of care. We'll also cover how stigma and bias can create barriers for those seeking treatment.
Joining me in this discussion is Dr Elizabeth Salisbury-Afshar, who is in the Department of Family Medicine and Community Health in the School of Medicine and Public Health at the University of Wisconsin. Welcome Dr Salisbury-Afshar.
Elizabeth Salisbury-Afshar, MD, MPH: Hi, thanks so much for having me.
Mukkamala: Glad you could join us. Um, can you share with our listeners a, a bit about your work with opioid use disorder? What's, what's a day in your life like?
Salisbury-Afshar: I am a family medicine, addiction medicine and public health physician. We recently moved to Madison, Wisconsin, about three years ago. And here I hold a few different roles. I don't really have a day, an average day, if you will. I work on our inpatient addiction consult team.
I work in the outpatient setting, providing addiction treatment services in a federally qualified health center for folks predominantly with Medicaid or who are uninsured. I'm also the medical director of harm reduction services at our state health department. And then I'm the program director of our public health residency here.
So, I continue to kind of hold these dual roles in the clinical and public health space, which I think gives me a unique perspective about sort of big picture, what's happening as it relates to the overdose crisis that we continue to see in this country, as well as what's happening in the clinical environments.
Mukkamala: Thank you so much. We're very grateful for the path your career has taken and especially grateful to have you here to talk about the treatment of opioid use disorder. So, the need for our discussion today is clear. There's been a significant change in opioid involved death rates. And as we've all seen, these death rates have increased by 38% to a record number of over 100,000 just this past year.
Prescription opioid involved deaths has also increased by 17%. Heroin involved death rates have decreased by 7%, but it's still 7 times higher than it was just in 1999. And synthetic opioid involved death rates, excluding methadone, have increased by 56%. So, staggering numbers. Let's start with what we mean when we say opioid use disorder, or OUD. How do you define opioid use disorder?
Salisbury-Afshar: I know you mentioned in your introduction that we are increasingly understanding the many social factors that impact the likelihood that someone develops addiction. So again, if we're looking at a hundred people who are using opioids, for example, we expect that about 10 to 20% of them would go on to develop.
addiction. And we know that factors, social factors like living in poverty, like lower educational attainment, like higher rates of isolation, adverse childhood experiences, all of those factors increase the likelihood that someone goes on to develop addiction. And so those social determinants of health play a really important role in the likelihood that someone will develop a use disorder.
So, to answer your question, how do we define it medically? Opioid use disorder is the term that came out in the DSM-5 in 2013. I always like to remind folks that the old terms from the DSM-4, the terms of abuse and dependence, are no longer medical terms and we should try really hard not to use them in medical environments.
And so, when we start to consider sort of, does someone sitting in front of us have a use disorder. The term opioid use disorder is a medical diagnosis, and that diagnosis is not based on how much or how often a person uses a substance, but instead is based on their symptoms and behaviors related to their use.
And so, a quick shortcut to remember how to think about the symptoms of opioid use disorder are by the three C's. Which are cravings, continued use despite negative consequences and loss of control around one's use. In a clinical setting, we do typically use the DSM5 symptoms, and there are 11 of them, to assess the severity of this diagnosis.
And so based on the number of positive symptoms someone has, we would then make a diagnosis of mild, moderate, or severe use disorder. But again, for individuals not working in addiction treatment, it can often be easier just to remember those three C's of cravings, continued use despite consequences and loss of control.
Mukkamala: Thank you. Can you give us an overview of treatment options that are available for opioid use disorders are generally accepted standard of care?
Salisbury-Afshar: Sure. So, often when folks in the United States and not limited just to medical clinicians talk about treatment, really what they're referring to is often sort of behavioral counseling or residential treatment.
And I think it's really important to acknowledge that for opioid use disorder, we know that particularly for folks with moderate to severe use disorder outcomes are significantly better when someone uses a medication as part of their treatment plan. So, there are currently three medications that are FDA approved to treat opioid use disorder in the United States. They're probably familiar names at this point.
But the medications are methadone, buprenorphine. Buprenorphine has a lot of trade names, Suboxone is probably the one most familiar with. I'm going to be calling it buprenorphine throughout, but just know I'm really referring to the entire, sort of, all of the buprenorphine products. And extended-release naltrexone, trade name is Vivitrol.
Again, I'm going to be referring to it as extended-release naltrexone, but just know that I'm talking about that injectable medication. We know that all three of these medications will increase the likelihood that someone remains engaged in treatment and it reduces the chance that someone continues to use illicit opioids. Methadone and buprenorphine specifically are also associated with reduced overdose mortality and reduced all-cause mortality, which is why these medications are generally considered first line.
Finally, there are many different types of psychosocial treatment and counseling that are available. There truly is no one size fits all option and we never want to withhold medication treatment because either counseling isn't available or the patient isn't interested or doesn't feel ready for it.
And counseling supports can range from anything such as peer support or mutual aid, things like smart recovery or NA, could be individual counseling or going to a more formal treatment program, outpatient or residential treatment program. So, lots and lots of options in that behavioral, sort of psychosocial treatment space.
Mukkamala: And what does success look like and how effective are these opioid use disorder treatments that you mentioned?
Salisbury-Afshar: Those are great questions. And I think one of the interesting things when we look historically at how we've measured success in the substance use space is that we've really mostly defined success as complete abstinence. And one of the most common metrics that we've measured is toxicology. So, what does the urine toxicology say? If we're serious about considering use disorders, substance use disorders as chronic health conditions, this model doesn't really make sense. Because, you know, with other chronic health conditions, whether we're talking about hypertension or diabetes, we generally recognize that improvement is likely leads to improved health outcomes, right?
So even if someone's blood pressure comes down significantly, but maybe isn't perfect yet, or if their A1C comes down significantly, but isn't optimized yet. We don't throw in the towel and say, “well, clearly this was all a waste. Nothing's getting better.” In addiction, often that's what's happened.
Historically, if we don't see perfection, then it was a quote failure. And we're starting to see some changes in this space, but I think it's really important to acknowledge that historically we've measured success solely as what is the urine show today. We haven't looked at people as whole people sitting in front of us.
We haven't really had great ways or at least haven't tried to measure reductions in use that maybe, you know, there's still something showing up on a toxicology report, but the person in front of us is reporting significant reduction in use. They went from not working to working. They went from not seeing their family to seeing their family.
Lots and lots of positive movement, right? But if the only thing we look at is full abstinence, we're not going to see the great strides people are making. So, I just want to say that first and foremost, it's really important that we continue to push ourselves in the research and addiction space to not solely look at toxicology as our only measure of success. Because to be honest, in the eyes of our patients, it's usually not the one that matters the most, right? It's all those other factors in their lives.
You asked about how effective or efficacious the treatments are. Even when abstinence was used as the primary metric, when we compare outcomes for addiction treatment and specifically opioid use disorder treatment with medication to other chronic health conditions, medications for opioid use disorder are generally as effective as treatments for things like hypertension and diabetes.
So chronic conditions are chronic conditions. It often is a long path for folks to sort of get to that optimization. And so, we see rates of effectiveness as being very comparable. And then I just will say one more time, each of the medications are associated with reduced illicit opioid use and increased retention in treatment. But so far, based on all the research we have, only methadone and buprenorphine are associated with reduced mortality.
Mukkamala: Got it. Great information. Thanks. Unfortunately, there are major barriers to access and to use these medications, including regulatory barriers. So, an example is that access to methadone is mostly limited to opioid treatment programs, OTPs. So, can you share barriers to access that you've encountered when taking care of your patients and how you overcame them?
Salisbury-Afshar: I really appreciate that you pointed out methadone. Methadone for the treatment of opioid use disorder is probably the most regulated drug that we have in the United States. For example, as a primary care doc, I am legally allowed to prescribe methadone for pain in my office.
But methadone for opioid use disorder can only be dispensed in a specially licensed opioid treatment program. And so, you'll notice I use the word dispensed, not prescribed. So, for patients who are interested in taking methadone as part of their treatment plan, they are required to show up every single day or in some states, six days a week, they have to show up to that clinic every single day.
And so, this is a pretty serious life commitment. You know, if you think about individuals who have children, individuals who are trying to work, this is a really, really onerous process. The other challenge is that most of our rural communities in the United States don't have any access to methadone. So, I'm originally from a really rural community in central Southern Illinois, a farming community. And our nearest OTP or methadone program is an hour drive and there's no public transit.
So, if you don't have a car or you don't have someone who can drive you essentially two hours every single day, you know, many days in a row for literally months, then methadone is just not even a viable treatment option for you. I do want to acknowledge that in Canada and Australia and many Western European countries, they have developed, you know, many alternative mechanisms to being able to ensure access, including pharmacy dispensing, to be able to get over some of these geographic barriers. And I'm highly hopeful that we will see some federal regulation changes to be able to increase access to methadone. So that's methadone.
Buprenorphine barriers are a little bit different. Historically, anyone who wanted to prescribe buprenorphine had to complete some additional training and be able to apply for a special waiver from the DEA.
Thankfully that barrier has recently been removed, but we continue to see a lot of challenges around buprenorphine prescribing that I would sort of largely put into three categories. The first is really around education. And I think I'm guessing many of us, myself included, didn't receive a lot of education or training on how one, you know, to work with people who use substances. Two, to have enough exposure to feel comfortable prescribing these medications.
And so, there's still a pretty significant educational and training gap. The second one, which probably won't be a surprise to anyone, is capacity. So, I work with a lot of primary care clinicians who will tell me, like, “Elizabeth, we did our training. We feel really ready. You know, you've given us algorithms and protocols. We have, we're ready to go. You know, you can start sending us patients.”
But then when we say, “okay, well, when's your next available?” It'll be three months out. And then we say, “okay, well, typically when you're starting treatment for, with buprenorphine, you see folks at least weekly.” And when we look at their schedules, you know, there's just no way.
And so, I think this sort of capacity issue is really, really a big one right now. The way that some health systems have been able to address this is by having really robust teams. So, they may have nurse care managers, they may have peer recovery coaches in the primary care or behavioral health setting.
The challenge is that in most states, we don't have reimbursement mechanisms to pay for those models of care, especially not in primary care. So, you know, the challenge, the big challenges I continue to see are sort of this educational gap, general capacity, especially in primary care.
And the last thing I would say here is just that stigma always comes up. And I think it would be, uh, naive of me to say that stigma doesn't exist any longer. There is tremendous stigma across our entire society against people who use drugs and against people with substance use disorders. I do feel, as somebody who's been training a lot in this space for, again, at least the last decade, it's gotten significantly better. But without question, we still have a, we still have a long way to go.
Mukkamala: Yes, for sure. Can you elaborate a little bit on some examples of the stigma that exists that lead to barriers to accessibility in particular populations perhaps?
Salisbury-Afshar: Absolutely. I think that the way that we as a country set up our methadone regulations are a prime example of stigma at a societal level. Specifically, in the [19]60s, we made these decisions that methadone was something that had to be done separate from the rest of medicine. By regulation, the only thing you can do there is dispense methadone. You can't provide other medical services. That's a prime example of sort of historically we set up these systems to say addiction is not part of traditional medicine.
It's not even part of traditional mental health care. It's this thing that needs to happen separate and we're going to separate people. I think that has been tremendously detrimental to all of our efforts nationally to actually integrate care. And so, I think there are a lot of systems-level sort of decisions that were made honestly based predominantly because of stigma that we are now trying to figure out how to dismantle.
We routinely see that individuals who are incarcerated have their medications for opioid use disorder stopped while they're incarcerated. These are often folks who have a preexisting diagnosis, who already are being treated by a medical clinician in the community with these medications. These are first line treatments.
They are evidence-based treatments. And we are particularly concerned about folks who are incarcerated because we know that when an individual leaves incarceration, their risk for overdose skyrockets in those first two weeks after they leave. Despite all of this, and despite the Department of Justice putting out public guidance that not offering medications while folks, not offering medications for opioid use disorder while folks are incarcerated is a violation of the Americans with Disabilities Act, we literally see this every single day.
And sadly, many of us who work in the field have had patients who have died post release because their medications are stopped while they're there. Unfortunately, we see similar things in the hospital. We see many hospitals around the country still are not diagnosing or offering medications for opioid use disorder for patients who are hospitalized.
And so again, we continue to see that, you know, lots of barriers, the educational gaps and sort of uncertainty and how to do this, sometimes challenges with linkages in community. But we see lots of folks in, in locations where they should be getting standard of care, they're not getting a standard of care, which is really putting them at risk.
Mukkamala: Yeah, that's both disappointing and shocking, but a good example of how clinicians need to be more aware of their patients' access to treatment. We can't just assume that when they leave our office with a prescription that everything is going to be okay. What else could clinicians keep at the top of their mind as they consider treatment options for patients with opioid use disorder?
Salisbury-Afshar: One of the most important things to know is actually, where are the local treatment providers? And who are the recovery-oriented organizations in your community? And I know a lot of times when I talk to clinicians, they feel really uncertain about how to even refer. And I often reflect, like, if we in the health care field feel uncertain, think about how families feel, right?
And we hear so much in the news these days about these really proprietary treatment programs who sort of prey on families who are feeling really desperate. And so, I would encourage anyone who sees patients in any capacity to just do a little bit of online searching to figure out. Many states at this point, especially after all of the federal funds and opioid settlement funds coming out, many states have created state-based online treatment finders.
If you don't already know, figure out what that looks like in your, in your home state, and then look at what's in your own geographic area, in your county, and what types of services are they offering. So sadly, even though we know that medications for opioid use disorder are first line treatments, we know that people have better outcomes when they use medication, our most recent national surveillance suggests that only about half of all licensed substance use disorder treatment programs actually offer medication.
So just to tell someone to like, “Oh, I know there's a program down the road, you know, for example, you should try that one.” If we don't know what they're offering, you know, it might be that that's one of the one of the 50% of programs that actually don't offer first line medication treatments.
So, really important to know, are there methadone programs in your community? Where are they? Which, you know, providers or which clinic sites are offering buprenorphine and where are they? And then what other types of sort of behavioral services are in your area? Some states are even using 211 to be able to help people facilitate which programs they can go to.
And I finally want to acknowledge the other thing you might want to do in your searching is just to find out if you have any local peer recovery or recovery coach organizations. They often have different names in different states.
These are people with lived experience, often with two plus years of recovery from their substance use disorder, who really just serve as a support to individuals who are struggling with substance use. There are many amazing things about working with peer recovery coaches, but one of them is that they know the community resources like the back of their hand.
So, if you know nothing else, just knowing where your peer recovery organizations are can be really helpful because that's their role is to help people navigate the services that exist in the community. If you can figure out at least a couple of those things, you're off to a good start to being able to help patients figure out how to navigate these systems.
And sadly, it is not straightforward. So, it does take a little bit of digging.
Mukkamala: So, let's go back to the three FDA approved medications for the treatment of opioid use disorder, methadone, buprenorphine and naltrexone. Let's do a little pharmacology, if you will. Can you walk us through what we need to know about each of them?
Salisbury-Afshar: Sure. Methadone was actually the first of the three medications that was FDA approved for the treatment of opioid use disorder. It's been around since the sixties. It is a great treatment for opioid use disorder. I've described some of the federal regulations. So, I think on a very practical level, when I'm talking to patients about methadone, the first thing I ask is, “What do you know about it? And here are the places where they are in our community. Could you get there every day?”
And if they look at me and say, absolutely not, then sadly, our conversation stops there, at least until federal regulation changes. Because methadone is a full opioid agonist itself, the way in which the medication dose is titrated up is actually very heavily regulated by the federal government, but it is a full agonist. If someone was to take way more than prescribed, it does have some potential for overdose risk. But again, at the methadone treatment programs, people have to go in daily and are monitored during those first months of care.
Just for clinicians, we do want to be careful if we're adding additional opioids on top of methadone. For example, if someone's hospitalized or has an acute procedure. And my biggest recommendation for clinicians is if you're working with a patient who's taking methadone and you're not sure if doses need to be adjusted or what other meds may interact, my best advice is just to get a release of information signed and work directly with the treatment program to be able to coordinate care and ensure safety.
The other thing I would just acknowledge, and this really applies to all three of the medications, is that we know that when patients are discontinuing any of these medications, there is an increased risk for overdose. Often when people are stopping their medication, cravings may go up. And so, if you're ever working with a patient who is trying to taper or discontinue their medication, making sure that they have all the resources possible, definitely making sure that they have naloxone, the medication that's used to reverse overdose, and all the social supports and other supports that are available.
Mukkamala: And next up, buprenorphine. What's most important to know here?
Salisbury-Afshar: The good news is if you had heard about what we often refer to as the X waiver, that's out. You don't need that anymore. Um, anyone who has a DEA license to prescribe Schedule three substances can legally prescribe buprenorphine. The MATE Act does require all of us to get eight hours of education. And there's a list available on the SAMHSA website of the specifics around what's required.
Important things to know for folks who either are using buprenorphine as treatment or are considering it. With the ever changing drug supply and in particular with increasing fentanyl in the community and now xylazine, which is actually an animal tranquilizer that's being cut into a lot of opioids around the country, probably more so mostly in Philly, but we're seeing more and more, xylazine in other parts of the country. We are seeing that it's getting harder and harder to initiate buprenorphine. The risk, if you give buprenorphine too soon after someone's used substances is that it can precipitate withdrawal.
Patients and clinicians nationally are reporting more difficulty with this, and so we're seeing a lot of shifts in the way that we're initiating the medication. I wish I could say that we had a perfect answer right now to make sure that everyone avoids withdrawal. We aren't quite there yet, but we are seeing a lot of individualization of patient care.
We definitely always want to take patient preference into account. And I know that Melissa Weimer and colleagues have an article coming out in the Journal of Addiction Medicine in the next few months that will highlight sort of the state of the evidence right now. And so, I think the key takeaway here is that patients are increasingly concerned about starting buprenorphine because they're worried about precipitated withdrawal.
There are some great resources online about different ways to address this. And so, if you are a buprenorphine prescriber, I would just encourage you to stay abreast of the literature and stay abreast of what we're trying in different areas, particularly if you're in an environment that sees a lot of xylazine and that is where you're having patient report that there's a lot of precipitated withdrawal.
Other things, there are no recommended time limit for treatment. People can be on buprenorphine as long as it's helping and as long as there are no contraindications. And if someone is going to taper, the recommendation is that it's done very slowly. And again, we know that while folks are tapering or stopping medications, risk for overdose often goes up. So again, we want to make sure everybody has naloxone.
Mukkamala: Great. And now, tell us about naltrexone.
Salisbury-Afshar: Sure. So, I do want to acknowledge that naltrexone comes in two formulations. So, there is an oral formulation. However, we have found that for opioid use disorder specifically, the oral formulation is not recommended.
It hasn't been shown to be efficacious and in one study, potentially actually increased risk of overdose. So, if we are using naltrexone, we want to be, for opioid use disorder, we want to be using the injectable formulation. The injectable formulation lasts for about 28 days. And unlike methadone or buprenorphine, instead of it being an agonist or a partial agonist, it's actually an antagonist, meaning it goes to those opioid receptors in the brain.
It fully blocks the receptor for about a month. So, extended-release naltrexone can only be initiated when we're confident that someone has been able to be abstinent from all opioids for at least seven to 10 days. The risk if we give it too soon is that it can precipitate a really significant withdrawal.
There are some case reports of it actually even leading to ICU admission. So, people can get very, very sick. So, if you're going to be prescribing extended-release naltrexone for opioid use disorder. Just really important to have that upfront conversation about are you absolutely confident no opioids in the last 7 to 10 days because if we give it too soon, it could make you really, really sick.
I should also just mention, you know, because this is an antagonist, we know that people's tolerance is down while they're taking it. And there was a recent secondary analysis of this big trial called the X:BOT trial that was published in the Journal of Addiction Medicine in July of 2022 by Elizabeth Ajazi and colleagues.
And essentially this team of researchers found that when they compared extended-release naltrexone and buprenorphine from that original X:BOT trial, those in the extended-release naltrexone arm actually had a greater risk of overdose. This was a single study. They conducted the analysis slightly differently than the original team of researchers.
And I think my main point in bringing this up is that this is an area where we need more research. No available extended-release naltrexone studies have found a reduction in mortality. And now we have this single study showing a possible increase in mortality. And so, I would just say if you're working with someone on extended-release naltrexone, it's really, really critical that they understand that if they decide not to get the subsequent shot and return to use, their risk for overdose is much higher than it was when they were using because their tolerance is down. So, it's just a very risky time for folks because they have a very low tolerance. So, if they're going to return to use, they need to use less. Again, any patient who has an opioid use disorder, any patient who has any risk for opioid exposure, we really want everyone to have a naloxone.
Mukkamala: Yeah, and that was exactly going to be my next point about, um, mentioning naloxone, because it shouldn't be confused with naltrexone, which is what we just discussed. Naloxone is used as a treatment for opioid overdose, and we'll cover naloxone in more depth in an episode in the future on overdose prevention. As we reach the end of our session here, any closing comments?
Salisbury-Afshar: I think that regardless of what specialty we're in, we are all likely to meet individuals with opioid and other substance use disorders. And in truth, we likely all have individuals with opioid and other substance use disorders in our lives.
And so even if you're not an addiction specialist like I am, I would encourage all of us to, you know, make sure that we're using appropriate terminology. So, things like the term use disorder. Make sure that we are treating all people with dignity and respect. And if we are in a position where you might have the opportunity to prescribe naloxone, that we do that for anyone who could be at risk.
Mukkamala: Thank you. I'm glad we had this chance to talk about how the stigma of opioid use can create biases that stand in the way of patients having access to treatment. Thank you so much for your practical knowledge on this subject, but especially for your care of patients that often, for all the reasons we've discussed, have such a hard time getting the care they need.
I mean, I really hope that your knowledge will help others expand the care they're able to give their patients. So, thank you very much, Dr Salisbury-Afshar, and thank you everyone for listening. And we'll see you next time.
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