Hello, everyone. My name is Dr. Andrew Saxon. I'm an addiction psychiatrist at the University of Washington School of Medicine in Seattle. I will be moderating today's webinar. We are fortunate to have as our presenter Dr. Christine Torres-Lockhart, who I will introduce in just a moment. Her topic today is opioid use disorder treatment, engaging in harm reduction in the area of polysubstance use. Next slide, please. Funding for this initiative was made possible in part by a grant from SAMHSA. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the Department of Health and Human Services, nor does mention of trade names, commercial practices or organizations imply endorsement by the U.S. government. Next slide. Today's webinar has been designated for a one continuing medical education credit. Credit for participating in the webinar will be available for the next 60 days. Next slide. Captioning for today's presentation is available. To enable the captions, click show captions at the bottom of the screen. Click the arrow and select view full transcript to open the captions in a side window. Next slide. Please feel free to submit your questions throughout the presentation by typing them into the Q&A area found also in the attendee control panel at the bottom of your screen. We will reserve as much time as possible at the end of the presentations for Q&A. Next slide. I am pleased to introduce Dr. Christine Torres-Lockhart, who is a fellow of the American Society of Addiction Medicine and is an Assistant Professor of Medicine in the Division of General Internal Medicine and Department of Psychiatry and Behavioral Sciences at Montefiore Medical Center in the Albert Einstein College of Medicine. She is the Founding Director of the Addiction Consult Service at Montefiore's Weiler Hospital. She is Program Director of the Addiction Medicine Fellowship and Co-Director of the Addiction Medicine Rotation for Medical Trainees. An addiction medicine and internal medicine physician, she leads the development and implementation of health system interventions to improve substance use disorder care in acute care settings and transitions of care to post-acute and ambulatory care settings. Dr. Torres-Lockhart, thank you for being here, and please proceed with your presentation. Thank you. Thank you for that very kind introduction. I'm really excited to be here and talk to you about things that I'm really passionate about in treating opioid use disorder, particularly in the midst of our current opioid crisis. I don't have any personal disclosures, but caveat, I use a lot of abbreviations, so I'll try not to. But if you see them, substance use disorder is SUD, opioid use disorder OUD, and I'll often shorthand medication for opioid use disorder as MOUD, and sometimes even refer to buprenorphine as bup. So please bear with me if I do. So these are our objectives for the session today. We'll be reviewing the epidemiology of the current overdose crisis and look at the role of psychostimulants in that. We'll also talk about some harm reduction principles and actually talk about some practical strategies that you can actually incorporate harm reduction into your own clinical practice and care. We'll review the evidence and talk about current initiation strategies that we have available for starting medications for opioid use disorder treatment, namely talking about methadone and buprenorphine. And then lastly, we'll talk about an approach to caring for someone who has opioid use disorder and has concomitant stimulant use as well. So whenever I give a presentation, I always really like to talk about the words matter movement and how important it is that the words that we use, whether it's in communication with one another, with our patients, and even within the medical record, because so often stigmatizing terms have really become ingrained in our medical vernacular. But we know that having them is really associated with barriers to our patients accessing effective treatments and even associated with negative patient outcomes. So I really urge all of us to move away from some of the terms that are more stigmatizing or pejorative that really center the disease in the conversation to really talking about more patient-centered language that, again, centers the patient in our discussion. So for example, we really want to avoid terms like addict, abuser, junkie, and instead use terms like person with an addiction, person with opioid use disorder, person who injects drugs. And then when we talk about either toxicology testing, either being clean or dirty, these are really nonspecific terms. So I like to just either say they're either negative or positive for a substance, and that can either be expected or unexpected based on what a patient has disclosed or what they're being prescribed. This idea of someone being clean, right, that's a pejorative term. And so really a preferred term would be someone who is in remission or in recovery or is an abstinence from their substance use. And then another one is this term medication-assisted treatment, so MAT. It's a small change, but really moving to the term more medication for addiction treatment, really because it's a small change, but the medication-assisted treatment term sort of implies that medications are sort of an adjunct or sort of like an add-on as opposed to the real backbone of effective treatment for opioid use disorder, which we know medications are, just like any other chronic medical illness, like we give insulin for diabetes, et cetera. And then lastly, narcotics is really a legal term with legal implications, not a medical one, so prefer to use the term opioids. And then also just to recognize that oftentimes our patients may identify with certain terms that I'm deeming here as potentially stigmatizing, and really to respect whatever preference patients have for terms that they refer to themselves as, but it's really important for us as clinicians or providers to use non-stigmatizing terms. So again, a call to action for all of us to sort of recognize these non-preferred terms in our own conversations and documenting, and really try to use more patient-centered language. So for our agenda today, we're going to talk a little bit about the epidemiology of the current overdose crisis. We'll talk about the role for harm reduction and practical strategies, review medications for opioid use disorder, and again, talk about a framework for stimulant use. So let's start a little bit with the historical context of really what's brought us to the current setting of our overdose crisis. So this is a graph that's looking at fatal overdose deaths from essentially 1999 to 2021, with time on the x-axis, and then the number of deaths on the y-axis. And here we see sort of the four different waves of the overdose crisis. So the first one really begins with the green wave here, pictured with prescription opioids, where we see that really beginning to rise and peak in the early 2000s, and peak in around 2010. And this really, we know, was kind of the result of a lot of different things, but one of them being really aggressive pharmaceutical marketing, and also with the advent of pain as the fifth vital sign. We see that sort of green line start to plateau and taper off as we sort of recognize the harms of prescription opioids. And there was a lot of, again, measures to try to curb prescription opioid prescribing and decrease it, which we know has happened. As prescription opioids declined, we sort of see the rise of the second wave. So this is in the purple line with heroin as being the driver of opioid deaths. And this was really just an indication that while the prescription opioids were decreasing in the market, people who were opioid dependent really sought out another opioid from the non-prescription market. And then we see in the 20-teens, essentially replaced in the blue line, the dramatic increase of overdose deaths with the rise of fentanyl or other highly potent synthetic opioids, as I often call them. And that's what we see really driving the overdose crisis now. Currently, though, we are in the midst of what people are terming the fourth wave of the overdose crisis with this red line, which I really think is the most concerning one, which are deaths involving both potent synthetic opioids like fentanyl and the analogs, but also psychostimulants. So things like cocaine, amphetamines, and methamphetamine as well. So as the drug supply has sort of become more potent in terms of the opioids with the rise of fentanyl and its analogs, we also see on the other end of the spectrum, the rise of more potent and pure methamphetamine drug supply as well. So we often see folks now using, because one supply has become so potent, essentially an opposite kind of drug to offset the adverse effects of that. And now we're seeing people use more substances and really seeing people using multiple substances as the rule as opposed to the exception. So if we look a little bit more closely, we can also see the trend of really how often fentanyl-only deaths are occurring over this sort of time period. And we see here in blue are the fentanyl-only deaths. And again, we see that dramatic increase in the early 20 teens. And then we also see sort of the role of what stimulant-only deaths are looking like here in the red, which looks like it's held pretty stable with around 15 to 18% over the years. But again, want to draw your attention to the dramatic increase in the purple section, which again are deaths due to both the setting of having fentanyl and stimulants combined. So we also know that different substances, particularly psychostimulants, their use really varies geographically here in the United States. So I want us to draw our attention to the leftmost graphs. And here on the top left, we see a map of methamphetamine use in the United States with the darker, the red-orange color are really showing higher rates of use. And we really see the West Coast and the Midwest being really large drivers of methamphetamine use in this country. But we know that temporally methamphetamine use has really been traveling eastwards. When we sort of look at the bottom left graph, here's a graph looking at cocaine use in the U.S. And again, we see the darker red and orange colors showing increasing rates of use. And that really is concentrated in the northeast. So again, you'll be seeing certain patterns based on where you're practicing, but hopefully we'll really be able to talk about how we can engage our patients in harm reduction around their use patterns, regardless of which stimulants they might be using and where you practice. So now that we're seeing sort of the emergence of multiple substances, I really want to talk about the term polysubstance use. So previously it really had no clear definition and it's often found in the medical record, and it can be a stigmatizing term in the record. It has negative connotations and negative implications, and it's really not a very helpful or specific term to me when I'm really trying to identify what someone might be at risk for in terms of medical complications of their substance use. So I think now we're at a really critical time where it's important for us as experts to really define what this term means and use it thoughtfully. So first off, I think when we talk about polysubstance use, we really want to be clarifying how many substances are we talking about and what are those substances? And of those substances that someone is using, really thinking thoughtfully about are they meeting criteria for is this a use disorder or is this risky use or is this experimental use, and being really thoughtful about how we're defining the use of each. Also, we really want to be thinking about how people use these substances and how they use them together and trying to identify are there primary substance use disorders at play or secondary use disorders and how people are thinking of their use disorders themselves. When we also talk about polysubstance use, I think it's important to be really specific about the timing of the use. Are people using these drugs totally simultaneously? So they're mixing it together. It's being used in the same exact mode. And for example, this might be like speed balling where someone is mixing heroin or fentanyl with cocaine and injecting. Or are we talking more, is this more sequential use where someone is using, say, multiple substances in a single sitting or episode like smoking marijuana and cannabis and drinking alcohol? Or is it these are just uses that happen to be happening on the same day but not necessarily the same episode? Because I think it's really important that we think about how people are using these because it will help us identify essentially what are the motivations for them using multiple substances and actually trying to identify potential opportunities for intervening and treating. And how do we sort of help people, keep people as safe as possible or engage them in treatment for their multiple use disorders? So oftentimes when people are using multiple substances, they may have lots of different motivating factors and trying to get at them is really important. So are they using two substances together to sort of enhance the effects of one substance? Are they using two substances together to essentially offset the potentially negative side effects of another drug? Or are they using a substance to potentially withdraw from another substance? I think, again, really trying to get at what are the motivators and the etiologies is important so we can figure out interventions to keep people safe and engage them in treatment if that's what they are interested in. So now that we know and sort of better understand our patients are using multiple substances and we've sort of tried to get at how are they using those multiple substances, let's sort of transition into how we can engage them in really harm reduction with really practical strategies. And so I recognize that lots of you may practice in very different settings and also have different state or local laws dictating what you may or may not be able to engage your patients so important to know your local regulations. But again, just want to highlight the reason we're seeing all these deaths and why we want to engage our patients in harm reduction is to recognize that the drug supply has become incredibly toxic and incredibly unpredictable with the rise of highly potent synthetic opioids. So really I'm talking about fentanyl and the fentanyl analogs, which we know are upwards of maybe 50 times more potent than heroin and 100 times more potent than morphine. We're also seeing the emergence of nidazines, which we know are even 20 times more potent than fentanyl. And when we think about fentanyl, we know it's incredibly lipophilic, it readily crosses the blood brain barrier and can really contribute to why people experience such rapid onset of effects, both for euphoria, contributing to the positive reinforcing effects of fentanyl, but also to the potential adverse effects as well. We know that fentanyl is being found in things that are marketed as opioids, so things like heroin, dope, but also in lots of pressed pills being marketed as opioids, but also pressed pills that are being marketed as other things, benzodiazepines, stimulants, ecstasy, cocaine, methamphetamines, etc. So again, it's a very toxic drug supply that can be really unpredictable for folks. I want to take just a brief minute to talk about xylosine, which is not an opioid, but it is now becoming a more frequently seen adulterant in the drug supply. So again, it's not an opioid, but it is an alpha-2 agonist, much like clonidine or dexamethamidine. It's not been approved for use in humans, and it's used really as a veterinary anesthetic, but it's a sedative, so it really helps to potentiate the sedation of other opioids like fentanyl. And the idea is thought that, you know, a fentanyl euphoria or sedation is pretty short-lived, and so xylosine is being added to the supply to help prolong the sedating effects of fentanyl. It's associated with chronic, poorly healing wounds that can be really hard to manage for some folks, and we're seeing it being found in more and more fatal drug poisonings across the U.S. Philly has been a place that has been seeing that very early on, and it's been in their drug supply for quite some time, and it's now been growing in the New York City supply as well, which is where I practice. I just want to underline that even though it's not an opioid, we still really want to use naloxone in overdose reversals, because very often xylosine is found in opioid or fentanyl containing drug supplies, which we know naloxone is effective for, but also recognizing that chronic use can lead to its own sort of xylosine withdrawal, which is not really well understood and may require treatments with things that are not opioid, like alpha-2 agonists, like clonidine or even benzodiazepines. So now let's really get into what is harm reduction. So just like in any other chronic illness, people with opioid use disorder can have various goals and readiness for change, and as people potentially move through these various stages of change from pre-contemplation to contemplation to preparation, we recognize that until they're in an action or maintenance phase, they may still be using substances. So while they are still using substances, harm reduction is really a set of policies and programs and practical strategies to really reduce the harms that we know are associated with ongoing drug use. The idea is we really meet people where they are, particularly with regard to whatever stage of change they're in, encourage some positive change and not require people to stop using substances as any sort of precondition for that sort of support or treatment. It can also be really empowering to empower patients with these practical strategies so that they can decrease harms to themselves and also morbidity and mortality that we know happens with ongoing substance use. So what exactly is harm reduction for opioid use disorder? So first and foremost, it's overdose prevention. So it can be as simple as just the counseling we provide our patients around their substance use. So if you get, start with smaller amounts, really go low and slow, avoid mixing multiple substances, particularly multiple sedating substances. Test your drugs with testing supplies. There are readily available fentanyl and bilazine testing strips available to patients directly or through community-based organizations. Really advising folks to not use alone, so use with someone else around. So if something did happen, someone's available to help with overdose reversal. And then also being very generous with naloxone training and distribution to help prevent overdose deaths as well. If someone is an injection drug user, really advising around safe injection practices, making available sterile supplies and equipment. Again, just advising people on more sterile technique, not lifting needles, avoiding high risk areas, so the lower extremities or neck. And then depending on where you practice referring to syringe exchange programs if those are available. And then lastly, just basic medical care, screening for HIV, hepatitis C, linking to care when that's appropriate, providing HIV prep and pep, again, when that's appropriate, and just making sure folks are vaccinated against viral hepatitis like hepatitis B and hepatitis A. And then of course, screening for any STIs and treating them as necessary. So as mentioned, as one of the techniques we sort of have to help prevent overdose deaths, we have drug testing. And so these are really at-home test strips that folks can use, again, as a way to empower people to know more about what they're using, given that the drug supply is so incredibly toxic and unpredictable. So there are many readily available, primarily fentanyl and xylosine test strips that people can use. We offer them in our inpatient addiction medicine consult service. We offer them in any of our outpatient addiction medicine clinics, in all of our substance use programs and methadone clinics, but also these are frequently offered at many community-based organizations or addiction programs, et cetera. We frequently provide the fentanyl test strips to anyone using things that they think are opioids, certainly anyone using any pressed pills, anyone using stimulants, just because we know it's found in sort of all of these supplies. And we really prioritize providing xylosine to folks who are using opioids, because that is the drug supply it's most frequently been found in. But again, emerging data is starting to see it found in other supplies as well. But again, they're really easy to use. They're very much like an at-home pregnancy test. But the one thing I counsel folks is the caveat on reading the test. One line, one sort of pink line, is really means there is that substance present, which is a little bit counterintuitive. So I'm just careful to reiterate that with patients as well. And also come up with a plan. Like if this is positive for fentanyl or xylosine, like what are you gonna do? Are you not gonna use it? Are you gonna use maybe less of it? Make sure someone else is around. Make sure you have Narcan around. Try not to mix it with any other substances, et cetera. Again, really help you come up with plans with your patients. Again, another strategy that's really simple is just like, let's have our patients not use alone. And that is one way to just decrease their risk of a fatal overdose. So one way that we can do this is there's actually this very cool hotline called Never Use Alone. People can call in, they kind of say where they are, and they stay on the line with someone as they use. So if something were to happen, if something were to happen and they become unresponsive, that person on the line can sort of alert emergency services and send someone over. This is something I readily give out to my patients. There are overdose prevention centers. So there are technically only two above ground sanctioned ones in the United States. Both happen to be in New York City, but there are many internationally. And there's a lot of evidence and data to support their use. Decreasing morbidity, mortality, no deaths have ever occurred in these facilities where people are being supervised. And very importantly, as they've launched here in New York City, we haven't seen any changes in crime or disorder in the surrounding areas from where they've launched. So again, really important data to hopefully expand these services in other potential places. There's this really wonderful, this American Life podcast episode called The Call, which really sort of details a lot about this never use a long hotline, following like a really moving patient case. The person who was on the line with the patient who had an overdose and also the EMS person who responded. So I urge you all to take a listen if you can. And then again, one of our backbones of really preventing overdose deaths is providing naloxone for overdose prevention. So the most common preparation that we provide is the intranasal form in a four milligram dose. And we know that naloxone is an opioid antagonist or an opioid blocker. So it's gonna block the effects of any other opioids during an opioid related overdose. It takes just about two to five minutes to have an effect. It can last for about half an hour. When it's sent as a prescription, you usually get two sprays in every prescription order sort of pictured here on the left, but sometimes depending on your health department, they may also have overdose prevention programs where they distribute them. This is just a picture of the ones that we have here in New York City. You of course get the two doses, but you get some other supplies and information as well. And just a reminder, I do the teaching with anyone I give a naloxone kit to. So of course, anyone who happens to have opioid use disorder anyone on OUD treatment, anyone who cares for or lives with someone with opioid use disorder, friends, caregivers, anyone who wants a Narcan kit, I really support and help educate. And so just teaching them, reminding them, what are the steps of what does an overdose look like? What does someone look like? What does someone who's unresponsive look like? What is their breathing doing? Are they, have their color changed? Do they look gray or blue? Are they not breathing or abnormal breathing? And reminding folks, first, you want to call 911 and let them know you're going to administer a naloxone to actually administer it intranasally. And then sort of wait, you know, about two to five minutes. If there's no response, administer a second dose in the other nostril. And then if someone does feel comfortable and trained can help support their respiratory system with rescue breathing. And if not, to put that person in recovery position to protect from an aspiration and really stay with them until help arrives. And then I just sort of asked folks to sort of like, that was a lot of information. Tell me how you would sort of teach this to, you know, your partner or whoever it is you live with and just do some teach back to make sure all the important steps were relayed. So this is some data that just really reminds us that providing naloxone to lay people is effective and it's evidence-based. And it's really important to provide to our patients and their loved ones or folks that live with them because it's critical to preventing that overdose. Because of course someone can't use it on themselves. And so when we look at data of like when naloxone training and distribution happens by community programs, like syringe exchange programs, they're incredibly, incredibly effective at saving lives. One study showed that one in four kids that was distributed in a syringe exchange program was used to reverse an overdose in the next six months, which I find really astounding. And it's not something we can say a lot in medicine, but really having this around can help someone save a life. So this is just sort of a quick highlight of really like the amazing services that a syringe exchange program does outside of just exchanging sterile syringes. So outside of the syringes, they provide sterile supplies for use. So everything from the filter to the cooker to the whatever is being used to dilute the medication or substance in. And all of this really helps people not reuse their own supplies and not have to share supplies with other people. So really reducing the risk of any sort of bacterial or fungal infections that can lead to really high morbidity like osteomyelitis, endocarditis, bacteremia, and even sort of more simple abscesses and cellulitis. And again, by preventing reuse and sharing, really decreasing transmission of HIV and hepatitis C. They also offer peer services, case management, referrals to substance use treatment and mental health for folks who are interested. And again, just a reminder that these are evidence-based practices and we have a lot of data to support that these interventions really do reduce harms to both individuals who are using substances, but also communities. Here are a couple additional resources. So Next Distro is an online harm reduction organization that can help provide supplies to areas that don't have local SEPs. And then also safersubstanceuse.org has really wonderful guidance for safer use for both clinicians, providers, but also patients as well. So now let's review a little bit about evidence-based treatment for opioid use disorder. So this is the natural history of use disorder. We know as someone who is opioid naive, when they start to use, they get sort of the euphoric effects through the new opioid receptor and with continued repetitive use, they develop tolerance such that it takes more of that medication or substance to achieve that same euphoric effect. And those are those peaks we see with each continued use, but diminishing effects. And then with time we get really dependence such that really people are entering the cycle of using the substance, then developing withdrawal and craving, and then using again to relieve that withdrawal. And it's that really vicious cycle that we hope to break by using opioid agonist therapy, either methadone or buprenorphine, so that we can break that cycle, treat the withdrawal symptoms, help someone feel normal without euphoric, and really break them on the cycle so that they can focus on other things in their life instead of just tolerating and trying to figure out how to manage their withdrawal and craving. So when we talk about medications for opioid use disorder, we have three FDA approved ones in this country, buprenorphine, methadone, and naltrexone extended release. Buprenorphine and methadone are the opioid agonist that I'll primarily discuss. And then naltrexone is the opioid antagonist and the opioid blocker, which I'll discuss a little bit less. But opioid agonist therapy, so methadone and buprenorphine are really the mainstay. They're the most effective and the first line treatments for opioid use disorder. And this is because they are the medications that are associated with the most positive outcomes, including the most important ones in which they actually decrease mortality and decrease overdoses. All of the medications help to decrease non-prescribed opioid use and help keep people in care. But again, only the agonist treatments also help to prevent HIV, hep C transmission, and improve maternal fetal outcomes for pregnant people. I wanna dive a little bit more into the data really around the mortality benefit we have with buprenorphine and methadone. So this is a national sample of 40,000 insured patients who had opioid use disorder and it followed them as they sort of entered treatment for their use disorder and looked at them three months down the line, 12 months down the line, and looked at what were their hazards or their risk of having an overdose at those time periods or a serious opioid related complication. And here we see that when you compare to inpatient detox, residential care, only intensive outpatient treatment, other behavioral health treatment, the only intervention that was showed to be statistically significant in reducing overdoses was treatment with buprenorphine or methadone. So not even naltrexone, only treatment with buprenorphine and methadone reduced the risk of an overdose at three months by 76% and reduced the risk of an overdose at 12 months by almost 60%. These are number needed to treats of two to save a life. We do not have many medications and medicine that are this efficacious and underutilized. We know they're effective, but they're also very underutilized. Less than one in five people who has opioid use disorder in this country gets these medications. So why do they not get evidence-based treatment? I think first and foremost, it's stigma. Addiction and opioid use disorders are highly stigmatized as both medication and treatment options in this country and the systems in which they're delivered are also really stigmatized. They're also really, really siloed. So methadone treatment and opioid treatment programs is incredibly siloed and highly regulated at a federal level. And they're just not incorporated into general medical care like treatment of many other things that we consider chronic illnesses. I think some of that is changing as we see like the emergence of things like inpatient addiction consult services, where we really sort of try to integrate addiction care into general medical care. But again, it's still very, very siloed at the systems level in this country. And it's sort of perpetuated by how all of this work is reimbursed, how payers pay for it, and just the like providers and practices that deliver this care. So lots of work for us to do. Yeah, so even how medications for opioid use disorder delivered varies a lot in this country. So here we're looking at a map of the US, we're looking at counties. The blue counties are the ones where opioid treatment programs exist and methadone is able to be accessed for OUD in an outpatient setting. And we see that only 20% of US counties have an OTP and that there's a huge regional variation in where those OTPs are located with some states not even having a single OTP, making this a really effective medication that's also totally inaccessible for so many people in our country. When we look at buprenorphine and its availability in the US, we also see a huge segregation of care. So when buprenorphine was first made available in 2000 with the data 2000 to provide OUD care outside of an opioid treatment program, and we follow with time, we really see that the uptake was really in primarily white patient populations. When we look at the payers who were really able to access this treatment more and more readily over time, we see that those who were privately insured or those that were self-paid were also the ones that were more likely to be able to access buprenorphine care. So again, white populations with a higher SES were more likely to access this treatment. Now the X waiver is eliminated and so anyone with a DEA license prescribed, and I really hope that some of this movement really provides the impetus we need to improve equitable access to these lifesaving medications. Okay, so when we talk about starting these medicines for opioid use disorder, again, opioid agonist, buprenorphine and methadone are the ones that save lives, and which one you start is really based on patient preference, what's available in your area, and also the medical comorbidity someone has. Again, the underlying statement is that maintenance treatment is really the rule and detox is really not treatment. It can put someone at greater risk of harm. A detox goes through a tapering. Someone may leave with a decreased tolerance, and if they go and relapse using what they may have used before their detox, they have a lower tolerance, and it actually puts them at higher risk of an overdose. So again, maintenance treatment is really what we're going for. In terms of buprenorphine, there are lots of ways we can initiate it, and I'll sort of review the three major ones we have now and talk about the evidence and how to have that conversation with your patient, but really recognize we have lots of ways to do it. The data is sort of early, and we really need to be engaging our patients with good shared decision-making to find the best plan for them. Now in the era of sort of very potent synthetics like fentanyl, we want to consider using doses upwards of 24 or 32 milligrams. We're seeing emerging data that this may be more effective for people with those higher tolerances and staying in care, and we also want to consider using things like long-acting injectables because these are able to provide a more steady state of serum levels of buprenorphine over time, sometimes achieving higher serum levels than we can get with maximum dosing of sublingual buprenorphine, and this provides a much more steady state overdose protection for folks. Methadone, there's a new SAMHSA rule that just went into effect this April that really helps provide more flexibility for OTPs in initiating treatment and providing treatment for opioid use disorder, letting people use higher doses for initial dosing, which is important in this fentanyl era, providing take-home abilities on day one of treatment, and really an emphasis on providing harm reduction and patient-centered care. So when we talk about buprenorphine and how to initiate it, I think there are two really major principles in pharmacokinetic things that we want to remember. So one is it's a partial opioid agonist at the mu-opioid receptor. So here I say, you know, as someone has more and more and more buprenorphine, it activates at the opioid receptor. The y-axis is activity at the mu-opioid receptor, but it sort of plateaus, okay? And the other important thing is that it has a very high affinity for the opioid receptor. So it is able to displace any other agonist that is really at that opioid receptor that's around, whether that's fentanyl, heroin, methadone, oxycodone, whatever it is. And so these principles are really, really important for how do we safely start buprenorphine to really prevent any sort of precipitated withdrawal. And a precipitated withdrawal is really what happens if we take someone who has a lot of activity at the mu-opioid receptor because they have full agonists on board, give them buprenorphine, it takes all of that off, brings their activity at the receptor down really abruptly, and that's what's a precipitated withdrawal that can be very, very, very painful for a patient and potentially affect their ability to continue buprenorphine going on. So again, really important practical pharmacokinetics to understand about the medication. It was first approved for OUD treatment in 2002. There are also approved formulations for pain management, but they're dosed a little bit differently. Almost all the formulations are buccal, transmucosal, sublingual, or extended release. There really isn't an oral PO formulation because of first-pass metabolism. So when we talk about treatment for OUD, we're really talking about sublingual films in tablets, suboxone, or injectables like supplicate and brixotine. So again, there are three major ways to start buprenorphine. One is the standard initiation. It has the greatest evidence base. It requires people to stop opioids and go into withdrawal to initiate the treatment because of that idea of it having a very high affinity for the receptor and having a partial agonist quality. Another technique that is used is called low-dose initiation or microdosing, which doesn't require someone to go into withdrawal, and so it can be really helpful for people who have chronic pain, can't stop their opioids, have failed a standard initiation, really just don't want to go into withdrawal, or are a tricky transition because they're on methadone or fentanyl. And then lastly, there's a high-dose initiation that really comes out of the ED literature base, which we'll talk about as well. So this is just sort of like a standard way I do a buprenorphine initiation. We want people to be in withdrawal when they start so that the activity of their mu-opioid receptor is low, and then when we give the buprenorphine, we're able to increase the activity of the receptor and make them feel better. So we aim for a COWS score of around 8. I like to see some sort of like objective sign of withdrawal, you know, rhinorrhea, lachrymation, something opioid withdrawal specific. And really, the amount of time it takes is, it could be 24 hours for a short-acting opioid, like prescription short-acting opioids. Sometimes it takes up to 48 hours for fentanyl to safely start buprenorphine in this way, because even though it's short-acting, it's a very lipophilic, and so it can seep out of the fat stores for a long time for people who are frequent heavy users, and then even longer for something like methadone. Really starting with a 2 to 8 milligram dose, making sure it dissolves completely, up to 20 minutes underneath the tongue, and then sort of reassess in 30 minutes to an hour, and continue to re-dose every two hours as needed. Typically I max out at around 16 milligrams, sometimes 24 milligrams for someone who has a very high tolerance on the first day. The second day, really sort of adding up everything someone got in that first day, give it as a morning dose, and then you can add on additional 2 to 4 milligrams as needed doses, again maxing out at around 24 milligrams as well. Low-dose initiation is a strategy I talked about, which really the philosophy is that you're overlapping very small and escalating doses of buprenorphine as someone sort of maintains a full opioid agonist over the course of several days, really to get someone up to a dose of buprenorphine, where now buprenorphine is totally occupying the receptors, but it's in a very slow, gradual way that doesn't require someone to feel uncomfortable with withdrawal. It's nice for someone who had a precipitated withdrawal in the past and couldn't do a standard induction, doesn't want to go into a withdrawal, or again, someone switching from methadone or heavy non-prescribed fentanyl use, and here's sort of a sample schedule we use in our clinic in our inpatient stay that seems to work well. This just comes from a really nice review article, but again just underlines this idea that a precipitated withdrawal happens when you abruptly take someone from lots of full agonist activity to a lower activity with the buprenorphine as a partial agonist, whereas the low-dose initiation really takes them from this level to this level over days as opposed to 15 to 20 minutes. We sort of reviewed all of this, but precipitated withdrawal is the one complication that we want to be mindful of when we're starting buprenorphine because it is a partial agonist of the receptor with a high affinity, and it's very not subtle. People start experiencing very severe withdrawal within about 15 minutes of a sublingual dose, and again, it's more likely to happen if someone's starting with mild withdrawal when you start the initiation, you started with too little time between the last use of their full agonist in the buprenorphine, or again, if they're coming from methadone or heavy fentanyl use. The treatment is important. It seems counterintuitive, but the answer is more buprenorphine. Totally inundate all of their new opioid receptors with enough agonism from the buprenorphine that we can relieve their withdrawal. I often give eight milligrams every 30 minutes, sometimes giving 32 milligrams or more on a single day if I'm in the hospital. I also try to add on other symptomatic relievers like benzos or quantanines as well. Another way is to just stop the initiation and try again another day, but sometimes patients might not be willing to try again because it was such a negative interaction, so we don't want to lose the patient, so really, the first option of just getting more and more buprenorphine is preferred. High-dose initiation is, again, a really new emerging strategy really coming out of the emergency medicine literature, and the idea is people start buprenorphine while they're in withdrawal, usually with a higher cow score, so 13 or greater, and we give higher doses of buprenorphine to start, so giving upwards of 8, 16 milligrams as the first initial dose and re-dosing after an hour. It allows people to sort of stabilize on a dose much faster and has been shown to be effective for people who are using fentanyl. Small point, but just want to sort of recognize that we have two different real formulations for opioid use disorder for buprenorphine, the sublingual, which really shows us to have peaking serum levels in just a few hours after use, but those kind of quickly, that sort of quickly clears, so people may need more frequent dosing throughout the day to maintain steady state levels if they're on sublingual dosing, whereas an injectable, where this is sort of a weekly injection, you see it takes about a day to reach steady state levels, but really, that sort of maintains for the whole dosing period and avoids the peaks and troughs of a mucosal formulation, and so that might be beneficial for someone who is very symptomatic of the peaks and troughs of a sublingual formulation. Dr. Lockhart-Torres, I'm just letting you know we have less than 10 minutes left. Perfect. I would be remiss if I didn't talk about methadone. I talked a lot about buprenorphine. It's our oldest medication for opioid use disorder in this country. Also use it for pain, but it's regulated very differently. It can be given as an oral liquid or a tablet in a methadone program. We can give it at higher doses now because of the new SAMHSA rules, and we have a lot more flexibility in OTPs for how it can be delivered and how to really provide more patient-centered care. It's associated with more drug-drug interactions than buprenorphine, and also the one thing we worry about is QTC prolongation. So let's just wrap up with how I sort of think about approaching stimulant use in someone with opioid use disorder. Again, I want to be really specific about asking how they're using their stimulant and their opioid. Are they using the stimulant really just to offset the sedating effects of the opioid? If we engage them in treatment for their opioid use disorder, then maybe their stimulant disorder may decrease. So again, being specific about how they use to identify opportunities to engage in interventions and harm reduction. Make sure we're offering evidence-based treatment for their opioid use disorder. Talked about how buprenorphine and methadone are those things. Offer evidence-based treatment for stimulant use disorders. Technically, there's no FDA-approved medication, but the new ASAMAAAP released a practice guideline, including the data to support pharmacologic treatment that's off-label for some stimulant use disorders. And then again, harm reduction, harm reduction, harm reduction, overdose prevention. Give out naloxone, prescribe it. Refer folks for drug testing or provide those strips if you can, and refer to syringe exchange programs if they're available in your area. So just to wrap up, we're in the midst of an overdose crisis. It involves both opioids that are very potent and psychostimulants, making the drug supply incredibly toxic and unpredictable. We should be engaging in harm reduction interventions with our patients. They're evidence-based and they reduce harms to our patients and our communities. Engage people in evidence-based OUD treatment and agonist treatment with methadone and buprenorphine. We should be considering these other sort of novel approaches for how we start buprenorphine and considering long-acting injectables for patients, given the era of fentanyl and highly synthetic opioids. And then last but not least, let's make sure we're addressing other substance use aside from opioid use, particularly stimulant use for folks who are using both things with harm reduction and evidence-based treatment. So just my email, my Twitter, please reach out if you have any questions. I'm happy to take any questions. Yeah, so one question that was asked during the presentation was how do you handle precipitated withdrawal? You answered that right after the question was posed, which is to, in most cases, continue giving more buprenorphine. We just had another question here, which is a pretty broad but important question. What are some evidence-based pharmacologic treatments for stimulant use disorder? Sure, yeah. I will go back to the precipitated withdrawal one because I think it's important and it's happening to more of our patients now that maybe they've tried buprenorphine on the street or had a bad reaction that it's common. Our patients experience it a lot and it can really help and it really can plague their idea of even potentially thinking about it as a treatment option in the future. And so I do always give more buprenorphine. To be quite honest, I don't see a lot more buprenorphine making precipitated withdrawal a whole lot better, but I don't think it makes it worse. And at least at that point, someone is on the buprenorphine train and they can continue treatment. So really, I rely on more buprenorphine, but I give other adjuncts, load them up on quantadine, provide a benzo, treat the other symptoms with paramide, NSAIDs, things like that. Evidence-based treatment pharmacologic. Yeah, so I really urge you to take a look at the ASAM AAAP guideline. It really breaks down the evidence for cocaine use disorders and also amphetamine type use disorders. But just like for cocaine use disorders, talks about off-label use of bupropion, off-label use of topiramate, off-label use of stimulants, and then same with methamphetamine, amphetamine type stimulant use disorders. So some of the things they touch on are higher dose mirtazapine, combination high dose bupropion with extended release naltrexone, other stimulants. So again, lots of options, and it kind of provides a lot of guidance for what other comorbidities you might want to be thinking about when you're trying to choose an off-label option as well. And people should be able to get that guideline for free by going to the ASAM website or just do an internet search for the stimulant use treatment guidelines. So another great question came in. What can we as physicians do to reduce the stigma of opioid use disorder for the family of the patient? Oh, that's such a good question. I mean, I feel like the question is how do we reduce stigma, period, right? Like there's structural stigma that plays out in how we deliver this care and how substance use is criminalized in this country. And there's interpersonal stigma that people experience when maybe their family or society sees addiction in some way. And then there's personal stigma people experience. They're afraid to tell their providers that they're on methadone or something because they've had negative reactions in doing so. But so in particular for family of the patient, I always offer to bring loved ones into the conversation. Would it be helpful if you and I talked about it with your family together? I've done this a lot when I was doing my work in a methadone program. Methadone is so stigmatized, even though it's so effective with people really, again, seeing it as this exchanging one drug for another, which I really try to dismantle and get at the root of why they're saying it that way. But yeah, I just try to bring people into the conversation. And if anything, just empowering our patients to really just see this as another medication for a chronic medical illness. I have like no one's asking you when to stop your Lisartan or your insulin, you know? So why do we think of your Suboxone or your methadone in any different way? Thank you. We don't have any more questions from the audience. I'm going to ask a quick question since we have a minute or two left. I noticed that you usually, when you're prescribing Naloxone, you usually use the 4 milligram dose. There is an 8 milligram formulation available. And I'm just wondering, what's your rationale for using 4 versus 8 milligrams? Yeah, someone, here's my email. Please reach out. They asked for that. 4 milligrams versus 8 milligrams. Yeah, so I think this is an interesting question. I think not only do we have the 4 milligram Naloxone, there's the 8 milligram Naloxone dose. And there is now like Nalumavine, so other options for treating opioid overdoses. And I think we'll just have to look at the data, particularly with these newer options. I think my basic understanding is the data currently shows that 4 milligram doses do fine, even to reverse overdoses related to really potent synthetic opioids. And what we're seeing with the higher doses is not that they're more effective, but that people develop worse withdrawal and feel worse after. So I don't think we're saving any more lives. I think we're just making people feel worse after an overdose, which isn't really helpful. And same potential thing with the Nalumavine that we're seeing as it being approved for a new treatment for overdoses is that it's a very long acting. So yes, you may reverse an overdose, but someone's going to feel really crummy for a longer amount of time when they're opioid dependent. So again, how do we save lives without really putting our patients at more harms? Thank you. And there's one last question in the Q&A before we finish up. A follow up question, is there evidence for legalization of opioid to reduce the stigma of substance use disorder? Yeah, I mean, like Canada is one place to look. They are doing work around providing safe supply. So they have programs where they're providing fentanyl patches for people who have fentanyl use disorders or providing injectable hydromorphone for people who have refractory OUD to like methadone treatment, buprenorphine treatment, sustained release oral morphine they have there as well. And it is effective for some people. I think we have to recognize that we have some effective treatments here with methadone and buprenorphine, but it's a small toolkit and we need to be thinking about what are other evidence based options for refractory severe disease, which I know I certainly see in my clinical practice. Thank you. Could you advance to the last slide, please? And you can finish up. Should be one more. Yeah, sorry. I have a wheel of death on my end. Yes. So thank you very much, Dr. Lockhart-Torres for a very informative and wonderful presentation. Letting folks know that the ORN is a resource for no cost education, training and consultation. And we have consultants in every state and territory. And you can submit a request at the link shown on the slide. And then APA put in the chat a link to the post webinar survey. And it will be very, very helpful for our work trying to address the overdose epidemic if all of you who attended today could take that survey. So thank you all for being here. Thanks again for the presentation. We hope to see you next time. Bye, everyone.

opioid use disorder treatment

harm reduction

polysubstance use

SAMHSA funding

patient-centered language

overdose crisis epidemiology

psychostimulants and opioids

harm reduction strategies

evidence-based treatments

stimulant use disorders