Okay. Good evening, everybody. Welcome to today's webinar, Opioid Use Disorder in Youth by Dr. Justine Welsh. My name is Julie Kimmick, and I'm going to be your moderator for this session. This is the second of our spring webinar series on hot topics in the treatment of opioid use disorder and stimulant use disorder. I'd like to introduce our speaker today. Dr. Welsh is a child and an adolescent, as well as an addiction psychiatrist, as well as an associate professor in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine. She's the founder and director of Emory Healthcare Addiction Services and the medical director of the Addiction Alliance of Georgia, a collaboration between Emory University and the Hazelden Betty Ford Foundation. Dr. Welsh's research has focused on identifying barriers to accessing evidence-based treatment for adolescents and young adults with substance use disorders. She's been the recipient of award and grant funding from agencies including NIDA, NIAAA, and ACAP. Her co-edited book, Treating Adolescent Substance Use, a Clinician's Guide, was released in 2019. Dr. Welsh is an active advocate for enhancing access to quality comprehensive treatment for individuals with substance use disorders. She also provides expert consultation on reducing addiction-related stigma and enhancing medical education in the CDC's Division of Overdose Prevention, and serves as the associate director for the UC Irvine Train New Trainers in Addiction Medicine Fellowship. So welcome, Dr. Welsh. Thank you so much for having me, Dr. Gmeck. All right, I'm going to go ahead and share. All right, can everybody see that? Yes. Perfect. All right, so today we are going to be talking about opioid use disorder in youth, and again, thank you so much for having me today. All right, so moving forward, again, this is funded by SAMHSA for Opioid Response Network, and you've already seen a couple of these slides, so I'm going to skim through them pretty quickly here, but Dr. Gmeck has no disclosures, and as far as myself, I have no reported conflict of interest, but I do report out any kind of sources of funding, and I do want to highlight as we move on here support from a previous R21, which was funded by NIDA in the upper right-hand corner, and some of the original work I'll be discussing is derived from that specific grant. All right, so here's our outline for today. We'll first take a quick look at the epidemiology of opioid use in youth, then risk factors, especially for developing opioid use disorder, medication for opioid use disorder, and then barriers to care that are specific to this population, and some of the work that people, including my own team, are doing to address them, but before we get started, I know there was a kind of an intro about me academically, but from a clinical perspective, I do treat individuals ages 14 to 26 with substance use disorders, some of which have opioid use disorder, and my own specific research interests have been focused on opioid use disorder and how to retain youth in treatment. Now let's take a look at epidemiology. I'm going to spend a bit of time on this topic because I feel it's really important for people to understand the extent of the problem. This here shows treatment admissions to any level of care, so that includes outpatient all the way through residential, inpatient detox, for adolescents and young adults for opioid-related causes, and the peak that we really saw in the early 2010s. This data comes from all publicly subsidized facilities or those who receive some type of federal funding, which also again includes outpatient treatment, so the treatment episode data set for TEDS. However, so looking after the early 2000s, since 2011, we actually began to see a steady decline in treatment admissions by about 60% for adolescents and by 10% for young adults for opioid-related care, and not shown here, but these changes in opioid-specific related admissions actually occurred in the context of a decrease in overall substance-related admissions that mirror these same numbers, and while overall rates of substance use disorder are remaining relatively stable in adolescents and very much going up or increasing in young adults, it unfortunately seems like fewer individuals are presenting for care across the board or at least indicated by this study. So question, why are we all still so concerned? Well, despite people not presenting to formal addiction-related care within this age group, we've unfortunately still been seeing a rising number of overdoses, and opioid-related emergency department admissions have been increasing, and we've seen a rising mortality in youth with deaths attributable to opioids, as well as many other adverse outcomes. So this is still a very big problem on a national scale. Here you actually see the trajectory of overdose deaths in youth ages 15 to 24, and this is data that was published by the CDC, and rates have been steadily increasing over time. There was a dip in 2018, but then a dramatic increase since then, reaching to about 6,000 individuals in 2020 and even higher now. Now, this data is slightly different, and it's capturing youth ages 13 to 25. You can see here the split between overdoses in youth with opioids alone versus opioids with any other substance, which was historically lower, but now those deaths attributable to a combination of opioids and other substances has caught up. And you see the dramatic increase of 384% for opioids alone, and an increase by 760% for opioids and additional substances in that 13 to 25-year-old age group. Now, when thinking about where most people get opioids, specifically prescription opioids, I think it's good to know that the majority of them get them from a relative or friend and not a drug dealer. So this figure shows where a person obtained pain relievers for their last episode of misuse comes from the National Survey of Drug Use and Health, or the NSDUH, and almost 50% were given, bought from, or took from a friend or relative. So a primary point of intervention here, especially for youth, is limiting access. And I will say I have seen plenty of patients who've gone through their grandparents' cabinets, taken old bottles from people that didn't even realize they had them, or saved them from a rainy day. And literally this afternoon, I was just meeting with an adolescent who had used a number of Percocet that he had taken from family members. So again, this is continuing to occur and being incredibly mindful about limiting access to our youth. So let's take just a quick look at risk factors, which I think are important to acknowledge here, which have different influences on substance use, such as age of initiation, progression to a substance use disorder, and then associated risk behaviors that can present alongside substance use. Now, this is an oldie but a goodie. This is actually from 2005. But it's demonstrating how heritable substance use disorders really are. So here on the right side, you see a measure of heritability by substance in twins, and it's ranging from about 0.4 for hallucinogens to about 0.7 for cocaine. So opioids are somewhere in the middle here, with about 60% or so of that risk of developing a use disorder being genetic. And the way that we determine genetic risk has come a long way since 2005, which is when this was published. But it still demonstrates a significant connection between substance use and heritability, where approximately about 50% of that risk is estimated to be genetic. Now, many of us are aware that psychiatric disorders are a risk factor for developing substance use and vice versa. Here, data was examined from almost about 500 years. So we had 483 here, and those were ages 11 to 24 who had a substance use disorder. And whether or not the type of substance used was more likely to be associated with a specific mental health diagnosis. And so this was using data from Boston Children's, which has a fantastic substance use disorder program. And we found that patients with opioid use were significantly more likely to have an anxiety disorder, and specifically almost three and a half times as likely to have generalized anxiety disorder. One thing that I've heard time and time again, is that the first time, you know, when talking with a patient and you ask them, what did it feel like to use? I hear time and time again, that the first time I used opioids, I felt this overwhelming sense of relief. And understanding that and hearing that information helps me form the beginnings of a functional analysis of use that I can then use to better understand the behavioral work that needs to be done, as well as potentially treating any kind of co-occurring disorders or symptoms psychiatrically. So now this is just an association, I want to caution here, and certainly you can see a wide array of other disorders that can come alongside an opioid use disorder and often do. So I'm really going to focus on medication as far as interventions, which is the mainstay of treatment, even in youth, or at least it should be. So I'll be demonstrating why, unfortunately, that's not always the case in real world. But really, my point today is to hammer home medication for youth. So we know from extensive literature that MOUD, or medication for opioid use disorder, across the board has numerous benefits, including decreased mortality, improved treatment retention, decreased high risk behaviors that result in health complications like hepatitis C, and increased rates of abstinence for those who receive it. Unfortunately, work from a colleague of mine has found in certain populations that less than 5% of adolescents and less than 30% of young adults receive MOUD within three months of an OUD, or opioid use disorder diagnosis. And while that data is based on Medicaid claims, we know that despite having private or commercial insurance, the rates of receiving MOUD for young people are extremely low. So let's take a look at the three FDA approved medications for OUD, which include methadone, buprenorphine, and naltrexone. And really, the data indicates that all patients and hopefully what you get from today's talk is that also youth should be offered maintenance medication for opioid use disorder. But unfortunately, the vast majority of youth entering substance use disorder treatment for OUD are not provided buprenorphine, even though it is FDA approved for ages 16 and older, and has demonstrated to improve outcomes at rates similar to adults when taken adherently. So this table here highlights some of the key early papers that demonstrated improvements in outcomes from MOUD. And you can see here that one of them is the Woody paper, which is the buprenorphine and naloxone second to the bottom, which we will be taking a closer look at that's focused on youth. And you can see across the board that the percentage of opioid abstinence for this study, the Woody paper, which is focused on youth, is very similar to these other studies that were looking at rates of abstinence in older adults after taking MOUD. So let's take a walk through the three FDA approved medications for opioid use disorder in adults, and then the data for those in adolescence. So buprenorphine, just as a reminder, is a partial opioid agonist. It's the only addiction medication that is FDA approved for adolescents for any substance use disorder diagnosis. And that indication, again, is for opioid use disorder in ages 16 and older. So this here, this Woody study, was a Sentinel study in 2008 by Woody et al. that helped gain approval for maintenance use in this population. And so the buprenorphine group versus detox alone had less opioid use, less injection drug use, and higher rates of treatment retention. Now moving on to naltrexone. Naltrexone is an opioid antagonist, and it's FDA approved in adults for opioid and alcohol use disorders, and is off-label in adolescents under the age of 18. I will say that I commonly use this medication under the age of 18, and haven't actually had any issues with Medicaid or private insurance covering it in younger individuals down to the age of 14 or 15, which has surprised me. I'd say we have pretty good safety data for the use of naltrexone in this population. So this here, this Mitchell et al., was a recent larger randomized trial of 288 adolescents and young adults. You can see here the age group spans both 15 to 21. But unfortunately, at six months, only two out of the 82 that were randomized to that naltrexone arm received all of the doses. So adherence to this medication, even though it's a monthly injection, you would hope that the adherence would be higher, is incredibly poor, which is really just demonstrating challenges around treatment retention in this population. I do have a few adolescent patients who are just completely unwilling to receive an injection, and for whatever reasons have either failed or are not agreeable to trying buprenorphine. And I will sometimes just keep them on the oral naltrexone. In this case, given that these patients are residing often with some form of caregiver, I will craft a plan around daily observed dosing. And if that has challenges, we'll then integrate a contingency management plan around adherence to the medication administration protocol that we've all crafted. Again, that's not ideal. If you have anyone with an opioid use disorder, you really should be thinking about pushing them towards once-monthly injectable long-acting naltrexone versus the daily oral. But in youth, again, sometimes there's some workarounds because there's just a refusal to receive injections. And the reason that we're really cautious about sticking with the oral is that it can increase the risk of non-adherence with the oral formulation, and then that there can increase the risk of overdose and death, especially when the individual no longer has a tolerance, which is the case when you've been on an opioid blocker or antagonist, such as naltrexone. So, again, take-home here is if we're going to be using naltrexone, I try to stick with the extended release even in youth, but unfortunately it can be really hard to retain them on that medication. If pushed to using oral, I really try to do some kind of medication administration protocol involving a caregiver and using things like contingency management or incentives or reinforcers for adherence to the medication and the protocol that we've crafted. So, for methadone, which is the third FDA-approved medication for opioid use disorder in adults, it's been used for decades in adolescents, but there are no controlled studies here in the U.S., and adolescent must have failed other treatments first, so it's a fail-first medication. I've really never seen it used in adolescents. I just have not come across it. But, of course, patients would have to go to a federally regulated methadone clinic to receive it, unless that law changes with some of the legislature being currently proposed. So, calling out opioid withdrawal, buprenorphine is also the medication of choice in treating opioid withdrawal versus clonidine or supportive management alone in youth. This study by Marsh et al., the patients were actually, and they were ages 13 to 18, they were tapered off buprenorphine and then switched to naltrexone as an end goal. So, buprenorphine was literally just being used for detox purposes, but the buprenorphine group had a 61% successful conversion rate to naltrexone, while the clonidine group only had 5% of its participants convert to maintenance treatment. So, the use of buprenorphine over clonidine, which is considered supportive management in treating symptoms of opioid withdrawal, actually helps to retain patients in care, even if it's not the intention of keeping that individual on buprenorphine, which I just found fascinating and I really encourage my colleagues in local pediatric hospitals in our area to be switching over to using buprenorphine to manage symptoms versus using things like clonidine. Now, I wanted to give a quick mention about kratom, and I would kind of love to hear from the national audience who is seeing this, because I am seeing it all the time. Kratom is banned in certain states, but I do see a lot of kratom use in my practice, especially in younger patients who can purchase it here in Georgia from gas stations or online. So, for those of you who are not familiar with kratom, kratom is a plant from Southeast Asia, and it's a partial mu agonist and kappa antagonist. So, it's very similar to buprenorphine, and it can be purchased online or for gas stations, because it's not illegal at the federal level. People can develop a physiologic dependence to kratom, like other opioids, as well as symptoms of opioid withdrawal if you abruptly cut back, or you end up tapering down to, you know, a lower amount of kratom over a kind of a rapid period of time. And so some of these side effects that kratom can cause in itself can range from anxiety all the way to seizures. But really the primary reasons that I hear people are using it are for both pain relief, to self-manage symptoms of opioid withdrawal from other substances, and then also to manage anxiety or just get a sense of kind of mild high. The FDA has also published notices about the potential of contamination about kratom, including things like salmonella, nickel, and lead being in some of the products that are being sold. I would like to say that the active metabolite metragenin can be tested for in certain drug screens. And I, here at our clinic, we actually have a send out screen that tests for metragenin so I can see if some of my patients are using it. And that's really important because if you are going to be planning on starting something like naltrexone or an opioid blocker in someone who has a chronic history of using kratom, they could already have, you know, ongoing opioid dependence, physiologic dependence to kratom. And you could cause symptoms of pretty severe opioid withdrawal by giving naltrexone in someone who's regularly been using kratom. And we've seen that in our clinic as well. It is also becoming increasingly accepted practice for individuals who develop opioid withdrawal from kratom who have that physiologic dependence to use things like buprenorphine or MOUD to actually treat the addiction to kratom. So, again, I just wanted to shout out to kratom because I am seeing it all the time in our clinic now. So, for opioid monitoring, a couple points here. It's important to note that there's no evidence suggesting that a specific cadence or frequency of urine drug screens improves patient outcomes. And that holds true for youth. Opioids are really only detected for a short period of time. And something I do call out is that fentanyl is not tested for on point of care cups in CLIA-waivered clinics, which is a real issue because I have a lot of youth who are being unintentionally exposed to opioids, especially fentanyl, and they often don't realize that that's occurring. And then if you're looking for oxycodone or methadone, again, those really need to be spelled out. And once again, mitragynine, which is the active metabolite of kratom, can be tested for in some of the more comprehensive screens, which we do use at my location. I've had a number of questions from families and from other providers about, do you recommend a home urine drug screening for families if the parents are going to be overseeing that practice? And my perspective on that really has shifted over time. I used to be fairly opposed to it because of the negative dynamics that can form between caregiver and adolescent when they're being forced to submit samples of urine drug screens, and there's a loss of autonomy and all of the kind of developmental issues that can arise. With the pandemic, we ended up really switching a lot more to home monitoring and kind of creating practices and norms around that, and we're switching back to more of the in-house testing for adolescents here at our clinic. And I guess with many other things, including telehealth, we're a bit of a hybrid model now. So I have some families who engage in some home urine drug screen monitoring, and I have others that I've really advised that I think we need to be doing this in-house. I have no standardized plan for how often I'm monitoring my youth with opioid use disorder. It is really all individualized, and it's not meant to be punitive. It's not meant to be catching people doing anything, but really just as data to monitor progress. We also use a lot of contingency management in my clinic, and so some of those urine drug screens are often included in those contingency management protocols that we craft for really motivating youth to either engage in treatment, show up to treatment, take their medication, or have negative urine drug screens. So again, everything is very individualized. There's no one size fits all when it comes to the use of urine drug screen in youth. So let's take a look at those who do access medication and how many are retained in care, and I also really want to hit home at why some of our colleagues are hesitant to prescribe to this patient population. I've personally seen families and patients who have been very apprehensive about starting medications. When they do, they quickly drop out of care, and they're hearing mixed messages from either my clinic or previous providers about the utility of things like medication in younger patients. So we know that medication enhances treatment retention in youth, and this study uses Truven Medicaid data in individuals ages 13 to 22, and you can see with all three forms of MOUD, treatment retention was increased. So those who received buprenorphine within three months of an OUD diagnosis were 42% less likely to drop out of care, 46% less likely to drop out with naltrexone, and 68% less likely to drop out with methadone, and so this was again kind of an aggregate group of youth ages 13 to 22, but it's demonstrating that the use of MOUD does improve treatment retention. But I also want to call out, and we saw it before with the naltrexone extended release study, that even with MOUD, treatment retention in youth is lower than in their adult counterparts. So adults typically have rates of treatment retention between 40 to 50% very roughly at one year, and this figure here shows emerging adults, so it's going to be your 18 to 25 year olds, and rates of dropout at 12 months in opioid, in outpatient buprenorphine treatment. And so in this study, young adults had 57% treatment retention at 12 weeks, which is not great, but 17% at 12 months, while older adults had 78% at 12 weeks and 45% at 12 months, so significantly lower rates. And here's a separate study using a retrospective chart review of adolescents and young adults, and the age group here is 14 to 25, and a Kaplan-Meier curve was fit to describe the patient's retention time over 12 months, so treatment retention over a year, which was as low as 9% at that one-year marker. Again, this is ages 14 to 25, and that's incredibly low, with a loss of 25% of patients after that first visit, and only 45% retention at 60 days. MOED is also not only underutilized, I'm painting a really lovely picture here, but buprenorphine prescribing is actually decreasing in use. So this paper was recently published in Pediatrics, and it used IQVIA data to examine buprenorphine dispensing trends among youth 19 years old and younger from 2015 to 2020. And so this data set contains prescription data from retail pharmacies. And overall, the rate of buprenorphine dispensed to youth decreased by 25%, while dispensing during that same time frame for the older adults actually increased by 47%. So you have it going down in youth, and you have it going up in older adults. And what was really interesting was that buprenorphine dispensing to young women and girls declined by over 50% during the study period, compared with 38% among young men and boys of the same age. And we aren't entirely sure why that is happening, but more research is definitely needed in this area. And unfortunately, even when youth get to treatment for opioid use disorder or opioid related problems, MOED is often not used. So it's not even that they're not getting to treatment. We see treatment numbers declining, but those that get there don't even get it. So this is a study that my team published in 2021. And the left panel presents the percent for each age group entering OUD treatment. So you've got your ages 12 to 17, 18 to 24, and then 25 plus. And it's each age group entering OUD treatment over the course of year, divided by the estimated prevalence of opioid use disorder in the community. And so it's a combination of data sets using the TEDS and the NISTA, the National Survey of Drug Use and Health. And the right panel presents the percent for each age group with the planned referral for medication, divided by the number admitted to opioid use disorder treatment. So to put it in kind of a clear explanation, only 3.6% of adolescents with opioid use disorder based on population prevalence presented to treatment, compared to 22% of young adults who had opioid use disorder, and 45% of older adults. Now, once that 3.6% actually gets into specialty addiction treatment, only 2% were considered for MOUD in their treatment plans, compared to 56% of young adults and 93% of older adults. So if that is not an uphill battle, I don't know what is. You can literally see it is going uphill. So who does receive MOUD in this population? That was my question. Who is actually getting this? Well, again, previously, studies have found that younger individuals are less likely to receive MOUD. Females are less likely to receive than males, as well as non-Hispanic Black and Hispanic youth compared with non-Hispanic white youth. And one study found that only one in 54 Medicaid enrolled youth received pharmacotherapy after surviving an overdose when presenting to an ED or an inpatient unit. So even overdoses don't seem to trigger a prescription for medication in this population. So our team ended up doing two follow-up studies looking at this. And this here presents data examining the percentage of adolescents who've had daily opioid use or IV, intravenous opioid use, in the last 30 days and looking really at that group and what percentage received MOUD. And we figured they would at least be the ones to receive medication once admitted to care. So we use the treatment episode data set, which again, we've already kind of mentioned, but it reflects admissions to any level of care, so outpatient through detox. And we looked at adolescents ages 12 to 17 who met that criteria you can see listed there. So DSM diagnosis or ICD diagnosis of OUD, reported heroin, non-prescription methadone, or any opioid use of treatment intake. So that was kind of our broader group. And then we created a smaller subgroup that was that 30-day past history of daily opioid use or IV opioid use. And what did we find? Well, for our main finding, we did see a higher rate of medication for opioid use disorder among adolescents who had either daily opioid use in the past 30 days or current IV opioid use. But while those with daily or IV use had significantly higher rates, only one in eight individuals meeting this criteria, so about 13% received medication. The use of MOUD in this population significantly decreased with education, which we found was interesting. We weren't quite sure what to make of that, but previous research has identified that higher rates of school dropout and injection drug use in adolescents may increase the use of heroin and then could potentially increase the likelihood of MOUD, but we were just completely speculating there. Long story short, we just don't know. And consistent with other findings and previous research in our study, females were less likely to receive MOUD, and there were no further associations between age of first opioid use, the level of care that they had been admitted to, so it didn't matter if it was outpatient versus detox, referral source, treatment history, none of that actually mattered, or at least in this study was associated with receiving MOUD. So my take-home here is that opioid use disorder, from what we see, is likely being underdiagnosed in adolescents, that we are not prescribing as much as we should to use, and that even substance use severity barely serves as a predictor for receiving medication, with only one in eight adolescents who are using daily or injecting opioids receiving evidence-based addiction treatment in addiction treatment settings. So my thought here is that, although it might be a little controversial, if adolescents aren't receiving medication in these circumstances, either because they don't meet criteria for OUD or it hasn't been diagnosed, do we really need to be thinking about lowering that threshold for recommending MOUD, so that more use can be considered for treatment? So food for thought. All right, so I had to reflect. What had we seen in the literature? What was I, you know, kind of experiencing firsthand? Well, it seemed like people struggled to diagnose OUD in youth. Some that did were often opposed to MOUD or didn't work in a clinic that offered it. And there were patients that were coming to me who already had a preconceived notion about medication, having already been through other forms of treatment already. And more often than not, all I could do was convince them to take naltrexone. So buprenorphine was an even option for a lot of the patients that I have been seeing. Parents expressed to me a concern about risk of becoming, in their words, dependent on medication when their goal is really to have their child stop taking pills or using heroin. And so really, my experience is consistent with what we see in the literature, that there's been a lack of training, there are limited providers, there's issues with accessibility, and there are issues with stigma towards the use of medication in this population. So my group wanted to know more about the why, which I believe is important, and about what perceptions people had about medication in youth, specifically MOUD. So we ended up distributing an electronic survey to all of the licensed addiction treatment facilities here in Georgia, and we had 215 respondents from 73 different treatment agencies. And this table here really lists just out the different themes and sub-themes we found from over the 1400 text responses we received. So people were actually really eager to provide their thoughts about medication for opioid use disorder in youth. And you can see here, perspectives were more often negative than positive, and identified barriers to using MOUD, such as family-related issues and a lack of supervision and medication monitoring. There's also unknowns about how medication might impact the developing brain. People have concerns about that. I've also seen that type of concern with medications for other addiction treatment, like alcohol use disorder. So yeah, the findings weren't overly surprising for someone who works in this field, but it really was good to kind of itemize out and put down. And we were very strategic about only asking in youth ages 16 and older, knowing that that is the FDA-approved age for the use of buprenorphine. So all of these questions were specific to youth 16 and older. How do you feel about using medication, including buprenorphine, naltrexone, and methadone? And then we split them out. So overall, though, those who reported in the survey having received formal education about MOUD were more likely to believe in its use, to recommend it for adolescents, and not put on arbitrary requirements like having to fail abstinence-based treatment first. And I wanted to just highlight a few of the quotes that I thought were particularly impactful. So this first one here being, I don't believe suboxone should be the first intervention given to an adolescent due to the typically short-term, less than two years, use of opioids, the severity of their opioid use disorders, and the risk of abuse or long-term dependence on medication. Naltrexone would be a better option for adolescents on a case-by-case basis. And if you're interested, I'm happy to send this paper to anyone who reaches out to me. My email will be at the end. We did actually collect survey, not just kind of free text responses, about the perceptions of naltrexone versus buprenorphine versus methadone. And across the board, people were much more supportive of the use of naltrexone over buprenorphine or methadone. For our second quote here, I think medication should be the last resort after other treatment methods failed with regards to adolescents. So here's a prime example of the support for those fail-first approaches. And then last but not least, they will become dependent on those as well, taking that dependency into adulthood. I believe that adolescents need to learn to live as adults in a medication-free environment so they can carry those lessons later on in life. I believe they should only be used for detoxification in young adults and adolescents. And so really, this also highlights that kind of almost paternalistic approach to care that is not supported by the evidence base. So remember, overdose deaths going up. We really do just need more advocacy and education for people who have the ability to influence referrals to MOUD, not even just prescribers. So I ask myself, what can we do as providers to enhance treatment retention in youth who are receiving MLUD. Again, I've personally seen so many of my own patients dropping out of treatment. And so the next kind of logical step for my mind was turning to those behavioral interventions. So let's just quickly walk through some of the more formal behavioral strategies that have been tried to date. This, again, is specific to youth and the effects of combining therapy and medication. I want to be really, really careful here that I am not suggesting replacing medication with behavioral therapy, but saying that there may be more room to augment medication treatment with behavioral approaches than we've really been taking in this population. Now, I will say how we interpret the impact of therapy on adults receiving medication for OUD is a bit murky, likely because of how well the medication works and whether or not we're actually measuring some of the right outcomes. We have less data on this in adolescence and youth, and it's just been less extensively studied. So there are a few studies looking at both individual treatment as well as group therapies, some of which are listed here, and you all have access to my slides. But it's a bit hit or miss whether or not medication is included in that treatment plan. Pertaining to my own clinic and interests, I do want to highlight two studies here, one in adolescence and the other in young adults involving the adolescent community reinforcement approach, which is a therapy modality that we do use here in my clinic, and I've participated in research alongside Chestnut Health System, which is the certifying agency of ACRA. So in this first one by Dr. Mark Godley, they compared treatment response to a manualized form of therapy of ACRA, so adolescent community reinforcement approach, and the data here was collected from patients at over 50 substance use treatment organizations. It was part of a SAMHSA-funded study, and they looked at adolescents with primary opioid use compared to those who predominantly presented with alcohol or cannabis use who also received ACRA. And they found across the board that there were no significant differences in treatment initiation, engagement, or retention in care between the two groups. And this is really important because, as we just heard, youth with OUD tend to be very difficult to engage and retain even after that first visit, and ACRA has very strong supporting data for the treatment of cannabis use, and so they were looking at, you know, an opioid group and a cannabis group. And we've seen that in multiple studies, including the Cannabis Youth Treatment Study, or CYT study, which was one of the largest studies in adolescents with cannabis use. So showing efficacy in patients with primary opioid use that was similar to the response rates of ACRA with cannabis and alcohol use was really, really positive. And in a study of young adults ages 18 to 25, replicating that same adolescent paper and that same data set, we looked at similar outcomes of treatment initiation, engagement, retention, and again found no differences between primary opioid use group compared to the alcohol and cannabis use group. We also looked at substance use outcomes through 12 months, which I will show you here, and those included the percent days of using alcohol, cannabis, opioids, and other drugs by both the problem use groups. So the primary opioid use group, or OU, you can see the square, or the cannabis alcohol group, or the MAU, and we found no significant differences between the opioid and cannabis alcohol use groups in cannabis or alcohol. Basically, we saw very few differences across the board, but a significant reduction in opioid use in the primary opioid use group, and those declines persisted through the 12 months. Now, there were some individuals that were receiving medication for opioid use disorder, but that documented number in the study was actually too small to appropriately analyze, but again, some potentially promising results, and we have been using ACRA in my clinic, integrated within medication visits, and for example, medication monitoring adherence protocol is one of the protocols of ACRA. And just kind of a quick summary, this is outside of the scope, and we unfortunately don't have time to go into it, but the ACRA is one of the most common manualized form of treatment in this population, and it weaves in a number of different modalities, including CBT, MI, and family work, and it's really focused on increasing pro-social behaviors and decreasing some of the substance use. And some of the procedures I just outlined here, relapse prevention, the drug refusal skills, communication sobriety sample, functional analysis, and then medication adherence and monitoring is another one. So you can see the picture of the actual treatment manual on the right, and certainly feel free to search ACRA. There's plenty of information about it out there. And last but not least, we need to keep our patients alive in order to treat them. When I'm working with some of the trainees, I say my two main goals of this first visit is to get the person to come back and to assess for safety, because I can't treat a person if they don't show up again, and I can't treat a person if they're not alive. So those are the two main goals of an intake, is to just engage and make sure that we're handling any of the safety concerns. So this here is just a kind of a snapshot of a handout I provide to the patients in my clinic on using fentanyl test strips. And if you just Google DanSafe, this is the company that we use. And there's other companies out there. I'm not just endorsing DanSafe, and I don't work for them, but this is the one my clinic happens to use, and you can download it for free. We also have a naloxone and fentanyl test strip vending machine in my clinic, and all of it is completely free. And so we end up, I personally will walk the family to the naloxone vending machine. I'll stand there and stare at it, and I make sure that I'm putting naloxone in the family's hands, and really just engage both the parent or the caregiver and the adolescent in the discussion. And I have found just doing this and being part of it and seeing what it all means really decreases the stigma, the resistance towards accepting naloxone versus just sending with the prescription or saying, get it from your pharmacy. And I also give the feedback, if not for them or their child, it's for their friends, neighbors, or other family members. I also share with families that I've personally had a few adolescent patients overdose by using what they thought was only cannabis, and it had fentanyl sprinkled on top. And so I give naloxone to absolutely anyone who will take it, and then also fentanyl testing strips to absolutely anyone who will take it. But again, this is all legal in my state. I practice in Georgia. So do what's legal in your state. So in summary, MOUD is widely underutilized in youth despite an FDA indication of buprenorphine in ages 16 and older. Behavioral treatments are still very understudied. I only gave a snippet, but we don't have a lot of studies in this area. And in future research, I would really advocate of a lowering for the threshold of prescribing MOUD that may be required to capture those who either have OUD, who haven't been diagnosed, or those at a pivotal point in their use where they are using opioids daily or intravenously, but they have not maybe demonstrated the functional impairment needed for an OUD diagnosis. I personally believe that those individuals are at such high risk of overdose that they should be treated with medication. And importantly, we need more naloxone for everyone and education to improve attitudes and beliefs about medication or MOUD in youth. So thank you. You can see my email is justine.welsh.emory.edu. I welcome any kind of questions, et cetera, outreach. Yeah. Okay, great. Thank you so much for that very enlightening presentation. We do have some questions that have come in over the course of the lecture. So I've kind of grouped these and I'm going to go through by pretty much by medicine because there are some questions about buprenorphine. This dates back to when you were talking about the Woody study and somebody had asked about OUD lower buprenorphine doses, and then asked, do lower doses fill more MOUD receptors than in adults regarding adolescents? Yeah. So I don't know that I can answer, you know, a specific percentage of receptor occupancy for adolescents compared to older adults. I don't know that we've really done that type of research, but what I would say anecdotally and from my own clinical experience is that I do tend to start adolescents on lower doses and that the adolescents I have seen tend to be more sensitive to the sedating side effects of buprenorphine, even if they've been using other forms of opioids, which I found interesting. So I often start at a dose of two milligrams and I have just a wide variety or a variation, I guess you could say, of dosages. I have some 16, 17 year olds who are on a full 16 milligrams of buprenorphine and I have others that really never tolerate above two or even lower dosages. So I personally start low. I go slow. I do a lot of close monitoring. I have done virtual inductions with my older patients that I see, but with my younger ones, I tend to bring them into the office more. I also have seen nausea be a pretty significant side effect from buprenorphine in some of my younger patients. As far as that question was specific to buprenorphine, but as far as naltrexone, I stick with the adult doses of naltrexone. I may start a little bit lower because younger patients tend to be more sensitive to GI side effects. Kids tend to be a little more sensitive to GI side effects, especially those with anxiety and somatic symptoms. So I will sometimes do an oral challenge of 12 and a half before going to 25 before going to 50. But my goal there is still 50 and then still the, the normal adult load dose or not load dose, but just standing maintenance dose of naltrexone extended release. So I, I do some modification there, but the end goal is the same as adults. Whereas the buprenorphine, the end goal may be different depending on how much they tolerate the medication and how well their cravings are managed. That's much more individualized. That was a long answer, probably more than you wanted. I think it was perfect. We did have some questions about buprenorphine extended release products. So Sublicate or Brixani, what are your thoughts on using those in young people? And do you think use of those would help with retention? That's a great question. So we do provide Sublicate in my clinic. I will say that I don't have any adolescent patients who have wanted to, or even asked about transitioning to Sublicate. You know, the, the, the data that we have with extended release naltrexone really reflects a difficulty in switching adolescents to injectables and keeping them on that. And I, I kind of compare it to if you let an adolescent have autonomy in getting their immunizations, would they really stay up to date? So there's this kind of push pull there where I have just such a resistance to injectables in my younger patients. And I hear everything from, I have a needle phobia to, I just don't want the injection. I just don't want that to happen. And there can be again, some issues with privacy around naltrexone extended release and where the injection, you know, blue deal has to go. And, and just, I find that there's some resistance. So I personally don't have any adolescents on Sublicate. I'm not aware of any data specifically looking at adolescents on extended release buprenorphine, but certainly we have that data in extended release naltrexone to look at. So let me know. Sorry, somebody had wondered about like the FDA approval for those extended release products, the Sublicate and the Brixadi. Is it at age 18 or? Yes, I believe those are still at 18. I'm not aware that they've gone down yet. Maybe one day. Somebody wanted to know about what is the youngest age that you used the Suboxone or buprenorphine naloxone for opioid use disorder? What was your youngest patient? Yeah. So right now my clinic has licensure to treat 14 and older. And so 14 is my youngest. Okay. It's not to say that I wouldn't necessarily go lower if I, if they had a true identifiable opioid use disorder, elevated risk of overdose, you know, it's, it's harm reduction. If it's helpful reduces that risk. I probably would still use it, but personally it's 14. Okay. We now have some questions about the naltrexone. One person wanted to know how long somebody needs to be opioid free prior to starting naltrexone. Mm-hmm. So it, it doesn't differ from older adults and there are multiple different strategies for starting naltrexone where some people who are, are a little more, well, not eager, but who are, who are doing kind of more sophisticated lower dose micro induction, almost of the naltrexone and then starting it while someone is still using lower amounts of opioids, you can do that. But then there's the kind of historical seven to 10 days of being opioid free with naltrexone before starting it. And that's usually the, the number that I'm sticking with, including with youth, it's no different than with adults. Right. And somebody wanted to know if it would provoke withdrawal in patients who are still using, if you gave them naltrexone shot. Yes. Yes. If they have a history of physiologic dependence to opioids and a history of opioid withdrawal, giving someone naltrexone in that setting, absolute extended release naltrexone absolutely would, which is one of the reasons that we want to challenge with the oral naltrexone before transitioning to the extended release. Now onto the kratom. Somebody had mentioned that there's kratom seltzers that are being consumed recreationally. They advertise it as the first alcoholic free and cannabis free drink that gives a euphoric effect. What impact do you think this will have on you? Really bad one. I guess I can't see the future, but I think any way that we increase marketing of some of these substances to our youth from the way that, you know, nicotine is packaged and THC and cannabis products that are more easily accessible, more friendly to consume like a seltzer drink. I, I, that just gives me, that makes me concerned. Um, let's see here. What about, um, well, somebody had mentioned that that they treat youth with buprenorphine, but their challenge is that oftentimes they're made to come off of the medication before they can enter residential treatment. And they mentioned that this is a very frustrating, um, thing for them and scary in terms of overdose risk. I don't know if it's that way, you know, where you're practicing or. 100%. It's one of the reasons that my team was doing this study in Georgia. When I have to admit one of my own patients to a higher level of care, it more often than not, if they're on MOUD and it's not naltrexone, there's less resistance to keeping youth on naltrexone. And that's what we found in that study that I was referencing. Um, they get, they get their buprenorphine stopped immediately and, um, oftentimes very abruptly triggering symptoms of withdrawal. Uh, and it, it, yeah, I mean, it, it can be very aversive to someone who's treatment seeking. And then all of a sudden they're made to feel worse than they were. So, um, a hundred percent, it's a challenge where I practice. And one of the reasons I'm giving talks like this so that I can spread the word that, um, we have an evidence base for use. Uh, one question about your thoughts, about people not being retained in treatment. Do you think that the, that the young folks aren't, are stopping treatment because they want to return to drug use or they've returned to drug use, or do you think that they're stopping it to see if they're able to try abstinence? It's a great question. I would say probably mixed. I, I can't speak to any literature that I know about the reasons it, you know, there, there's probably some out there, but just from kind of my own clinical experience, I've seen the patients then come back, you know, six to 12 months later. And, um, oftentimes they've had an episode of return to use. Sometimes they've stopped medication, but they've come back for other reasons. Um, but I would say the majority, it's often a return to use episode, whether or not that preceded the decision to stop medication or not, um, that doesn't always sync up. So it might be they stopped medication and then later on they returned to use. Some have returned to use and then decided to stop medicine. Okay. I just noticed that it's 601. So I wanted to be respectful of your time and everybody else who's on the webinar. So unfortunately when there's a couple extra questions, um, that we're not going to be able to get to. Um, but if, if you do have a burning question, Dr. Welsh has, you know, kindly, uh, put her email here that you can send her the question through email. Um, I'd like to thank you, Dr. Welsh for your time today. Thank you for sharing your expertise and your research and thanks for all the important contributions that you've made to the field. And thanks everybody for attending. Thanks for listening. And tune in next week. We're going to have Dr. Tony Paison talk about methamphetamine toxicity. Thanks everyone.

webinar

Dr. Justine Welsh

opioid use disorder

medication for opioid use disorder

MOUD

adolescents

buprenorphine

behavioral therapies

extended release products

Kratom products