Thank you so much for being with us, welcome, and I am Dr. Gentile, I am a chair and professor of psychiatry at Wright State University in Dayton, Ohio, and I will be introducing my fine and smart colleagues who sit beside me here. Just to make sure we're all in the right place, this is Medical Treatment of Adolescents with Substance Use Disorders and Ascertaining Evidence and Strategies. So first I'll start with Dr. Neetha Bhatt. Dr. Bhatt is an associate professor with Wright State University. She's also an attending physician at Twin Valley Behavioral Health Care. This is a regional psychiatric hospital in Columbus, Ohio, and she's also the associate medical student director of the clerkship. And we also have Dr. Carrie Harper. Dr. Harper is also from Wright State University in Dayton, Ohio, and she is the division director for the Child and Adolescent Fellowship in Wright State University Department of Psychiatry, Dayton, Ohio. Next we have Dr. Ricky Steiner, and Dr. Steiner is a rising F2, or second year fellow, in the Wright State Fellowship for Child Adolescent Psychiatry, Dayton, Ohio. And we have Dr. Jesse Cannella, and Dr. Cannella is a recent graduate of the Boonshoft School of Medicine at Wright State University in Dayton, Ohio, and will soon be starting a triple board fellowship in Indianapolis, psychiatry, child adolescent psychiatry, and pediatrics. Thank you again for being here with us. Just by way of disclaimer, before we get started, the presenters have no relevant financial interest and no conflicts related to this presentation. We also just want to make sure that you understand the views that we're sharing today are those of the presenters, and do not necessarily reflect official policy or position of any of the presenters, current or prior universities, employers, or affiliations. And I will now be turning it over to Dr. Bott. Well, hello, everyone. Thanks again for joining us today. Before we get started, it is important to note that a majority of adolescents do not meet criteria for substance use disorders. However, substance use disorders are an issue with this population. So I work for the Ohio Department of Mental Health and Addiction Services, and I treat adults. So looking back at the data, you know, for the folks that I treat and my colleagues treat, a majority, a majority of our patients actually began using substances in adolescence. And so for that reason, I actually approached my colleagues and asked them to do this talk today to help me understand, to help educate me. So MAT, medication-assisted treatment, is now standard of care, right? It's standard of treatment for adults with substance use disorders. But unfortunately, it's far less commonly used for adolescents. I think we can all agree that evidence-based treatments must be established for the adolescent population, but of course for all populations. And the use of psychotrophic medications is certainly a critical piece of treatment. And of course, it should be considered with other modalities, combinations of therapy and community resources, that sort of thing. Due to the lack of large double-blinded placebo-controlled studies in children or in the youth, it's necessary to really extrapolate the gold standard treatments from adult studies and institute those in adolescent patients, of course, when clinically appropriate. So we're going to discuss that today. So the gold of today's talk, we want to identify the diagnostic criteria and, of course, clinical presentations of substance use disorders within the adolescent population. We will specifically touch on opioid use disorders, alcohol, and cannabis for today. We will look at varying evidence, efficacy, risks, and indications for the use of approved and FDA-approved and off-label indications, adverse effects, and the efficacy of MAT. So of course, like we said, management is multidisciplinary. It's complex. Both FDA-approved and off-label uses of MAT show great promise for this demographic and can really help actually reduce stigma, improve quality of life, increase societal integration of these adolescents and young adults. We hope you find this presentation helpful and are really thankful that you're here today. So without further ado, Dr. Carrie Harper, thank you for doing this. »» Thank you, Dr. Bott. Dr. Cannella and I will be presenting the evidence today and Dr. Steiner will be sharing some cases with some unique challenges. These cases are based on his patients and patients of other fellows in our Child and Adolescent Psychiatry Program. We've, of course, changed the details for privacy. Much of the presentation will involve evidence from studies including adolescents and young adults. Many of the studies point to similarities of very young adults with adolescents versus older adults, which in Child and Adolescent Psychiatry means 25 and over. Indicating those similarities include brain development, continued brain development and likely shorter duration of substance use compared with older adults who may have been using substances for decades. Let's first look at the prevalence of substance use disorders and attitudes regarding substances. As you can see from the data from monitoring the future, young adults have the greatest prevalence of substance use disorders. Alcohol use disorder is most prevalent in young adults and adults, while cannabis use disorder is the most prevalent disorder for adolescents. While young adults and adults report more problematic use of alcohol and prescription medications, there are a number of adolescents reporting binge drinking and misuse of prescriptions. Young adults, however, report both a substantial amount of problematic use and the belief that what we would consider problematic use is not really that harmful. As Dr. Bott mentioned, most adolescents do not meet criteria for substance use disorder. However, 90% of adults with a substance use disorder report first use in adolescence. An earlier use corresponds to a higher likelihood of developing a substance use disorder. One of the major concerns of substance use in adolescents is the profound consequences it may have on brain development. For example, we know use of some substances in adolescents puts one at greater risk for developing schizophrenia spectrum disorders. Both coping skills and neurocognitive abilities impact relapse, and adolescence is a time of growth. During periods of abstinence from the substances, cognitive abilities can develop significantly, leading to an important reason for treating substance use disorders quickly. These are the criteria for substance use disorders in the DSM-5-TR. I've replaced the specific disorder with the word substance here and italicized that as the same criteria apply for all substances. A substance use disorder is characterized by a problematic pattern of substance use that is impairing, including at least two of the following 11 criteria within a 12-month period. So the substance is often taken in larger amounts or over a longer period of time than intended. There's a persistent desire or unsuccessful efforts to cut down. A great deal of time is spent in the activities surrounding substance use, craving, recurrent substance use resulting in failure to fulfill major roles, continued substance use despite having persistent problems associated with the substance use, important social, occupational, or recreational activities are given up or reduced, recurrent substance use in situations where it's physically hazardous, substance use continued despite knowledge of having a persistent physical or psychological problem, tolerance, and withdrawal. We then have several specifiers, including early remission in months 3 to 12 and sustained remission after a year of meeting no criteria other than craving. We also specify if the person is in an environment with restricted access to the substance. The severity is categorized based on the number of symptoms, 2 to 3 for mild, 4 to 5 for moderate, or 6 for severe. What are some considerations for treating substance use in adolescents? As with anything in adolescents, peers have a large influence. Relapse is associated with social pressure, withdrawal, and negative affect. Successful outcomes, on the other hand, are associated with protective factors such as social connectedness, being goal-directed, and peer abstinence. Abstinence during the first year is promising for reduced substance abuse and symptoms of other psychiatric illness three years later. Adolescents are less likely than adults to remain abstinent after one treatment episode. There are varying degrees of success for prevention programs. Treatment of substance use disorders in adolescents has historically focused on psychosocial intervention. Even if there are evidence-based programs available, adolescents rarely achieve long-term abstinence, even with the strongest evidence-based treatments. Adoptional treatment is often multidisciplinary and multimodal. It is likely that psychosocial interventions with psychopharmacology improves treatment of adolescents with substance use disorders and helps limit the severity of the disorder and limit polysubstance use. Further studies are really needed urgently. In regards to pharmacotherapy, studies largely suggest FDA-approved pharmacological treatments for adults with SUDs are well-tolerated in adolescents. There is evidence for treatments to be used in opioid, alcohol, cannabis, and tobacco use disorders, including reduced use and cravings, improved retention in treatment, and reduced mortality. However, few adolescents and young adults are given pharmacotherapy for substance use disorders. While they may be few, there are randomized controlled trials indicating pharmacotherapies may be appropriate for the treatment of substance use disorders in adolescents. While treatment guidelines abdicate for early and effective treatment with pharmacotherapy, many treatment barriers exist for physicians and adolescent and young adult patients, including limited availability, stigma, and preference for psychosocial treatment only. This is a table summarizing some of the evidence for reference. You'll notice no treatment has grade A evidence. Medications for tobacco use disorder and specific treatments for cannabis use disorder and opioid use disorder have grade B evidence. So we'll start the specific disorders with opioid use disorder. Rates of opioid misuse among adolescents appears to be dropping. In 2009, there was a high of 9.2% of high school seniors reporting misuse of opioids. Now, well, in 2017, 3.1% of 12 to 17-year-olds reported misuse. However, there are still 99,000 adolescents who meet criteria for opioid use disorder in 2017, and there were more than 4,000 deaths due to opioid overdose in adolescents and young adults. Opioids are not infrequently prescribed to adolescents, with 15% of ED visits and 3% of outpatient visits resulting in a prescription for an opioid, usually for dental disorders or fractures. That may be concerning, as data suggests that prescription of opioids may later lead to a use disorder. Unfortunately, treatment for opioid use disorder is more difficult to attain for adolescents. Out of over 13,000 treatment facilities in the United States, only 26% serve adolescents. A quarter of those offer treatment for opioid use disorder, and only 15% offer opioid agonist treatment. Few offer inpatient or residential treatment. Facilities that offer adolescent treatment for opioid use disorder are more likely to be located in the Northeast. On top of the low availability of facilities, only 2.4% of adolescents compared to 26.3% of adults receive opioid agonist treatment at their first admission for opioid use disorder. There are several treatment barriers for adolescents, including a limited number of providers and treatment centers, high co-pays, and systemic problems leading to lower access by race and ethnicity. There are also local and national regulations of treatments, including regulations for additional training and certification, and documentation of other failed treatments. The stigma of replacing one drug with another in the case of opioid agonist treatment, and the use of medication as a last resort in adolescents, contributes further to these already existing treatment barriers. There are concerns among providers about the diagnosis, dosing, treatment duration, and the medication impact on developing brains. All these barriers point to the need for further research to address concerns and advocacy to address barriers and stigma. There is evidence for using medications to treat adolescents for opioid use disorder. Buprenorphine is a mixed agonist antagonist analgesic, which is FDA approved for the treatment of opioid use disorder in ages 16 and up. Major risks include respiratory depression and sedation, especially when used in combination with other substances. For buprenorphine, there are several studies that stand out. Marsh et al. compared buprenorphine with clonidine in 36 youth and outpatient treatment. Both treatments were tapered down weekly. The trial favored buprenorphine in several ways. Treatment retention, opioid negative urine tests, and initiation of naltrexone after the end of the trial period. Notably, both groups received relief from withdrawal symptoms and fewer risky behaviors. In a trial comparing 12-week treatment versus short-term detox in 152 patients aged 14 to 21, Woody and company found that the 12-week group fared more favorably. In the detox arm, buprenorphine was tapered over two weeks, whereas in the 12-week group, patients received a steady dose, which was tapered over weeks nine to 12. While opioid positive urine tests remained high among all participants after treatment completion, the 12-week group did have a significantly lower number of opioid positive urine tests during the 12-week study period and for the 12-month follow-up period. The 12-week group also had better retention in treatment, with 70% completing the trial versus 20% of the detox group. The 12-week group also reported less injecting and less opioid use overall, pointing to possible harm reduction. On further evaluation of this data, another study shows correlations with attrition and retention in treatment. Being in the detox group was associated with early attrition while the use of sleep medication in the detox group was related to retention, pointing to a possibly important factor in treatment considerations. In the 12-week group, past 30-day hallucinogen use is associated with attrition. On the other hand, early adherence to buprenorphine, early opioid negative urines, use of any medication in the past month, and lifetime non-heroin use was associated with retention in treatment. As we look at further duration of treatment, we see an even longer taper may have even better outcomes. In a study of 53 adolescents and young adults, those who underwent a 56-day buprenorphine taper had more opioid negative urines and better retention in treatment than those receiving a 28-day taper. Retention in treatment is an important outcome to consider. In a review of 103 charts of adolescents in an outpatient facility, Mattson et al found that retention was only 9% after a year. Over half of these patients did not continue treatment past two months. Longer retention was associated with opioid and THC negative urines, buprenorphine, naloxone positive urines, and female sex. Another retrospective case review may suggest that inpatient treatment and initiation of buprenorphine is a way to improve retention. In this study, 112 charts of adolescents using heroin were reviewed. Following the initiation of the treatment in an eight-week inpatient program, there was 24% retention at one year. Methadone is an opioid agonist used for the treatment of opioid use disorder in adults. There are regulations that there must be documentation of two or more failed treatments and assigned parental consent for use in those under 18. In addition, methadone can only be observed at specific regulated facilities, and administration must be observed for specific periods of time. Risks include respiratory depression, sedation, and QT prolongation. There are certainly fatalities, especially if used in combination with other substances. Due to these risks, methadone is reserved for more severe and long-duration opioid use disorder. There have been studies of methadone in adolescents. One compared methadone with buprenorphine in 61 adolescents with OUD. Those receiving methadone missed fewer days in the first month of treatment and were retained in treatment for an average of one year versus only two months. These are also studies in adolescents and young adults using heroin. Kellogg et al found that those in a first treatment episode in a methadone program had 48% retention in the first year. Those remaining in the program had a significant reduction in heroin use and trend toward reduction in cocaine use as well. Smith et al considered adolescents in a methadone treatment program 32% were retained at one year and a further 32% had planned exits from the program, either by dose taper and discontinuation or transfer to another treatment facility. Abstinence from heroin was found to increase over time in the program. And to discuss naltrexone. Naltrexone is a competitive opioid receptor antagonist. It's not FDA approved in minors. Risks include precipitation of opioid withdrawal, as well as increased sensitivity to opioids after discontinuation, leading to the need to warn patients that if they return to opioid use, there's a high risk for overdose if they take the same amount. In adolescents and young adults, there's a retrospective case series of 16 patients treated for opioid use disorder that shows promising results. Retention in treatment at four months was 63%. 69% saw substantial reductions in opioid use and over half had a good outcome, which was defined as substantially decreased opioid use, improvement in at least one psychosocial domain and no new problems due to substance use. In a recent trial, 288 adolescents and young adults in residential treatment were randomized to receive extended release naltrexone or treatment as usual, which could be buprenorphine and no medication after a buprenorphine detox. Most of the participants did not actually adhere to their assigned condition. They often expressed preference for a different one, which was allowed in this trial. Data was therefore analyzed as intention to treat, which was as randomized, as received, which was naltrexone versus non-naltrexone and as medicated, naltrexone versus buprenorphine versus no medication. Despite not being randomized, the demographics were generally the same among groups, with the exception that the group receiving naltrexone and choosing to receive naltrexone had tended to start the use of opioids almost a year younger, 15, about 15 years old versus 16 years old in the other groups. Results did show that those receiving naltrexone reported less opioid use at three months compared with non-naltrexone, buprenorphine and no medication. At six months, the naltrexone group continued to report less opioid use than the non-naltrexone group. Only two of the 82 in the naltrexone group received all the injections in the six-month follow-up period. On average, the naltrexone group received 1.3 injections post-residential treatment. And results did not differ among other substance use. And now I'll turn things over to Dr. Steiner for a case. Good afternoon, everybody. I'm Dr. Steiner, a CAP fellow at Wright State University. And as Dr. Harper said, the cases that I'll be discussing are amalgamations of patient encounters that I and my co-fellows have seen over this academic year. We have, of course, changed details for contact tracing for confidentiality and abbreviated the cases for time. So let's talk case number one. So we have a 16-year-old Caucasian male who presents with his parents for evaluation. He is pending legal charges for possession of narcotics and a lawyer suggested that the patient enter into psychiatric treatment. His parents report that their son was caught buying pills at school from another student. Both have been charged and suspended. The parents report noticing a difference in their son starting about a year and a half ago after his tibia was broken during a soccer game. He has progressively become more and more withdrawn since then, or from them, seemed depressed, and has different friends. As with many teens, the patient is resistant to talk with his parents in the room. Alone with a psychiatrist, the patient reports he was prescribed Vicodin for the pain after his leg was broken. He could not play for the rest of that season and was really disappointed. He also felt disconnected from his friends. He quickly found that taking the pain medication made him feel a little bit better. At follow-up appointments with his physician, he reported continued pain, gaining access to more prescriptions for medication. He often missed school during this time for pain and not feeling well. He ended up getting in trouble for missing assignments and serving detention. He eventually found a group of friends who used marijuana, alcohol, and whatever pills they could find around their houses. The patient also experimented with these substances, but obtained opioids wherever he could. In a review of systems, he met criteria for four, met four criteria for opioid use disorder, and he also expressed some depressive symptoms. What are our initial thoughts on treatment? Maybe we're thinking psychotherapy, maybe psychopharmacologic management, or a combination. His parents don't know the extent of his use. They caught him with alcohol once, with marijuana once, and now know about the recent trouble at school and the legal charges pending. What do you tell them? Let's hear more from the patient. The patient is open to treatment. He reports he misses his old life. He'll be a senior next year and misses playing soccer and his old friends. He wants to go to college. He agrees to tell his parents about his ongoing long-term opioid use while in the office with you. He's upset that they have to be told, but you encourage him that it will likely be better if his parents can see that he's willing to tell the truth. His parents are surprised and upset. You share the diagnosis with all of them. His mom says, why can't we just treat the depression? Then he won't need to use drugs. What would you say to her? With this patient, we next discuss various treatment options. Unfortunately, there are no facilities with inpatient options in the area. About an hour away, there is a treatment center with an outpatient program for adolescents. This family, with significant means, can make this work. The patient receives individual therapy, family therapy, and group therapy, along with buprenorphine naloxone, which is tapered at the end of the program. He does begin to feel much better and agrees to naltrexone extended release. What are the treatment considerations moving forward? There are many things to balance here, and as we heard, the evidence is that after one treatment episode, adolescents often relapse. So we can consider protective factors like family involvement and other relapse prevention strategies at the get-go rather than being reactive later on. Now back to Dr. Cannella. Hi, all. So next we'll be talking about alcohol use disorder, or AUD. So just as an overview, a study found that over a million adolescents 12 to 17 years did require treatment for AUD plus a different SUD in 2018, yet only about 80,000 actually received treatment services. This was based on a national survey on drug use and health. There's much debate over medication-assisted treatment, or MAT, when compared with harm reduction, absence-based recovery services, and psychotherapy alone. This is especially debatable and controversial when it comes to racial and ethnic disparities along with other minority groups, particularly in quality, frequency, and accessibility of mental health services or behavioral health services. Studies have shown that youth of color, and black youth specifically, have lower access to, and again, worse quality of behavioral health services when compared to their white peers. These disparities and the resulting impacts thus greatly necessitate further research into the matter and further efforts into how these can be combated societally. No medications as of 2022 are FDA-approved for alcohol use disorder treatment in children and adolescents. And thus, these slides will be a little bit different than the AUD section, as there are fewer studies and actually no FDA indications for alcohol use disorder in this age group. So we'll begin again by talking about naltrexone. In a study by Diaz et al. in 2005, Diaz studied six weeks open-label of naltrexone, specifically in five adolescents seeking treatment. Naltrexone was dosed between 25 and 50 milligrams per day, and results were assessed with the Adolescent Obsessive-Compulsive Drinking Scale, AOCDS, as well as liver function tests. At six weeks, the average daily drinks had decreased by 7.61 standard drinks compared to baseline, as well as significant reduction in alcohol-related thoughts. In a later study by Miranda et al. 2014, Miranda conducted a double-blind placebo-controlled crossover among 28 heavily drinking adolescents, specifically drinking at least four to five drinks per day on a drinking day in a month, with randomization to naltrexone at 50 milligrams versus placebo for 8 to 10 days, with washout in between. Naltrexone did reduce heavy drinking compared to placebo significantly and changed subjective responses to alcohol significantly. Naltrexone specifically was associated with reduced cravings, reduced amount of drinks per drinking day, and reduced number of drinking days on study days. Naltrexone was found to be well-tolerated with no significant adverse effects in this study. O'Malley et al. in 2015 conducted, at the time, the largest study among non-treatment-seeking youth age 18 to 25 with 125 participants, again reporting drinks of greater than four or five drinks on a day over the past month. This was a randomized controlled study with eight weeks of naltrexone or placebo. Naltrexone did not actually have any reduction in the frequency of drinking on drinking days, or sorry, the frequency of drinking days, but did reduce the drinking intensity on drinking days. Naltrexone significantly reduced drinks per day by about one drink compared to placebo and percent of drinking days where the estimated blood alcohol content was 0.08 by about 10% versus placebo, and this was based on reported number of drinks along with body size and age. There were large reductions in alcohol-related consequences seen in both groups with an insignificant improvement in the naltrexone group. However, a significant limitation in both studies by Miranda and O'Malley was the small effect size with only about one drink per drinking day and the time limitation. A further study, which will be discussed in a moment by DeMartini et al., found that at one-year follow-up, naltrexone treatment had unsustained group differences versus placebo. So again, in this DeMartini study in 2016, a longitudinal study of 118 young adults, 18 to 25, again reporting similar drinking levels over the prior four weeks was conducted with eight weeks of a double-blind randomized control trial of naltrexone versus placebo along with post-treatment behavioral basics follow-up at eight weeks, six months, and 12 months. Outcomes were percent days of heavy drinking, abbreviated as PHDD, percent days abstinent, PDA, and drinks per drinking day, DPDD. Percent of heavy drinking days was maintained as well as percent days abstinent post-treatment, but the actual drinking on drinking days was not, as shown in the next slide. So this graph comes from the study directly and shows the time relevance of the study. So for naltrexone, the drinking per drinking days did increase in the relatively short term from eight weeks to six months, sorry, increased in the short term, but then ultimately decreased by 12 months with no net change post-treatment. In the placebo group, drinking per drinking day did not significantly decrease but still had a significant benefit, sorry, resulting in a significant benefit of naltrexone, again, in the short term, eight weeks, but not at 12 months. There is thus a slower but equivalent effect of both at 12 months, but still positive, likely confounded by the behavioral monitoring and the basics interventions. Combined with in-treatment outcomes, again, from the O'Malley study, this suggests a differential benefit of naltrexone during active treatment with nonspecific improvements from behavioral interventions at one year or further. So next, discussed acamprosate. In its 2003 study, Niederholder et al. studied acramposate, which is an NMDA glutamate antagonist, which is known to reduce cravings through the mesolimbic dopamine effects and is FDA-approved for adults but not adolescents with AUD. In this double-blind placebo-controlled trial, 26 young adults or adolescents, 16 through 19, were studied, again, treated with acamprosate at 1332 milligrams daily versus placebo over a three-month period. Assessments were primarily subjective with interview, self-report and questionnaire, as well as lab screenings. By day 90, there were seven acamprosate participants versus two placebo participants who were found to be continually absent at a very significant confidence. Mean cumulative absence duration was 79.8 days in the study group versus only 32.8 days in the placebo, again, significant. Niederholder et al. in the same year conducted another study with disulfiram rather than acamprosate. So disulfiram inhibits alcohol dehydrogenase, which leads to a rapid increase in acetaldehyde upon alcohol consumption, resulting in non-ideal effects and leading to discouraged alcohol consumption. These effects include hypertension, flushing, tachycardia, palpitations, anxiety, et cetera. So in a double-blind RCT, again, Niederholder studied disulfiram in 49 adolescents, 16 to 19, with a 90-day detox period. The results were very similar to the acamprosate study, and after five days of abstinence, participants were randomized to the disulfiram versus placebo and followed weekly over this 90-day period. With very similar results at day 90, there were seven disulfiram participants versus two placebo participants who were found to be continuously abstinent, again, with very significant statistics. The mean cumulative absence duration was also greater in the disulfiram group, significantly at 68.5 days versus about 30 days in placebo, and disulfiram was well-tolerated in this group. N-acetylcysteine, or NAC, also has some promising, although preclinical, evidence in alcohol use among adolescents. A meta-analysis of seven trials did find that NAC was superior to placebo, specifically in reducing substance use cravings. The clinical findings regarded different substance uses, including alcohol, but also including cannabis, tobacco, and cocaine, again, with effective reduction in cravings among all of these substances, and a study by Navid et al. did find that there was appropriate use in pediatrics for NAC. Again, with less clinical evidence, animal studies do show NAC-associated reductions in chronic alcohol use. In animals, they have been consistently shown, the studies consistently show, that NAC is associated with reduced alcohol seeking, reduced symptoms withdrawal, reduced teratogenic effects, reduced toxicity, and chronic health effects of alcohol. The clinical evidence is variable for alcohol use in adolescents and in humans. A study in 2016 on a secondary analysis of a cannabis-dependent trial studying the effects of NAC on cannabis, but with a secondary analysis focused on concurrent alcohol use, did show that decreased cannabis use was associated with concurrent decreased reduction in alcohol when treated with NAC. But this was not shown in placebo. A study of 35 veterans with PTSD and concurrent SUDs, 82% of whom had diagnosed alcohol use disorder, found that NAC was significantly associated with decreased symptoms of PTSD, alcohol cravings, symptoms of depression as compared to placebo. In a study by Tomko et al., again, a secondary study of 75 adults with bipolar disorder, alcohol use was not significantly associated with NAC. No study has yet been completed studying NAC in AUD in adolescents or youth, although there is currently one underway expected to be completed in 2024. Topramate is most commonly used as an anti-epileptic drug and is a sodium channel and glutamate blocker known to increase GABA activity. While studied in adult alcohol use, it is associated with reductions in heavy drinking and relapse rates. This is a small double-blind placebo study for five weeks of topramate in heavy drinking youth, 14 to 24, again, not completed, but preliminary findings suggesting that topramate is well-tolerated and safe and possibly associated with about two fewer drinks per week in these participants. And back to Dr. Stein. All right. For case number two, we have an 18-year-old female experiencing homelessness who presents to the psychiatrist at the local youth homeless shelter. She presents with a chief complaint of, I need to stop drinking. She describes a history of conflict with her parents at an early age as she felt they never gave her what she needed. She explains that she has been couch hopping for months and has been staying with college-aged or older men she has met on dating apps. She has now been at the shelter for a few weeks. She's been feeling down and often irritable. She's had a hard time getting along with others at the shelter and has gotten into several arguments with friends. She feels very guilty about these encounters, leaving her parents' home on bad terms and her continued use of alcohol in excess of what she plans. In her chart, it is noted that the therapist has had reports from staff that they've had to clean up the shelter bathroom several times after nights of heavy drinking. The patient reports drinking more than intended, failed attempts to abstain from alcohol, craving alcohol, and having difficulty keeping her previous jobs due to showing up late and or hungover the next day after a night of drinking. So what diagnoses are we thinking? Are we thinking depression, alcohol use disorder? Yeah, I'm not trying to trick anybody. But what treatments would we consider? What would we be thinking we want to treat first? Both? There was a discussion with the patient regarding treatment for depression, which she reports began around 11. There was also a discussion about treatment for alcohol use disorder with the patient reporting that she started drinking at around age 14. The patient expresses desire for treatment for depression first without a medication for alcohol use disorder. She states that with treatment for depression, she thinks that she can stop drinking on her own. Resources are given for local AA groups as well, and she says she'll think about it. After discussing risks, benefits, side effects, and alternative options, fluoxetine 20 milligrams is started, and she's encouraged to continue therapy. At follow-up, the patient misses her next appointment, and you find out that she is hospitalized with alcohol-induced pancreatitis several weeks later. After the hospitalization, the patient feels defeated. She ran out of her fluoxetine, wasn't taking it consistently, and didn't feel like it was all that helpful. Given this recent health scare, however, she is willing to try naltrexone. Unfortunately, the patient still has not picked up her prescription for naltrexone and, to the psychiatrist's knowledge, continues to drink heavily. The patient is at risk for disrupting placement at the youth homeless shelter due to not participating in their programming. The psychiatrist enlisted the case manager's help for medication pickup and is waiting to hear about progress. While there hasn't been a follow-up appointment with the patient, the case manager was able to provide some new information. The patient is from Central America. She reportedly had a difficult childhood filled with exposure to abuse, drugs, and violence. In a customs office, she met with an official who documented that she was fleeing gang activity and said that if she returned home, she feared for her life. The case manager gleaned that the patient was not comfortable picking up her medication due to fear of being deported. How does this change how you would care for the patient? Would you do anything differently? This was my patient, and I think about this often. But for now, we're going to switch back to Dr. Cannella. So finally, we will be talking about cannabis use disorder, CUD. So cannabis is the most used illicit drug by adolescents in the United States. About 9% of marijuana users go on to develop cannabis use disorder with increased risk associated with increased earlier start of use. Commonly reported concerns among adolescents for wanting to decrease or stop use include the health consequences, feelings of self-control, impulse control, the costs, legal consequences, employment, and interpersonal conflicts. In a 2021 study in New Zealand specifically, early onset and frequent cannabis use in adolescence was inversely associated with high school graduation rates, levels of degree attainment, income at age 25, employment rates overall, and levels of relationship and life satisfaction, self-reported, even after controlling for confounders. As of 2018, no medications are FDA approved to treat CUD and that is still the case. So again, referring to the same study as early in the presentations by the National Institute on Drug Abuse, cannabis has been shown to be very accessible and used among adolescents. In fact, adolescents in the first category, about 50% reports easy access to obtain marijuana, with young adults reporting 61% positive access. And furthermore, 4% of, or sorry, that was adults, with 74% easy access in young adults. Furthermore, in adults, about 4% of participants in the study report being approached by someone offering the use of cannabis or accessibility of cannabis, versus 13% in young adults and 10% of adolescents under age 18 having been approached in the past month for accessing cannabis. So we'll begin again by discussing N-acetylcysteine, or NAC. This is the most promising drug in cannabis use disorder, with a number of other drugs having been studied at different efficacies. So common adverse effects of NAC are nausea and vomiting, diarrhea and sleepiness, but are typically reported as infrequent or mild. NAC is available over-the-counter, but this comes with risks of variable potency, variable purity, and inconsistencies in the same or different bottles of NAC when prescribed or taken. The half-life is about six and a half hours when taken orally. The mechanism of action is related to the conversion of L-cysteine to cysteine. This leads to glial cell uptake, and resultantly glutamate release with inhibitory glutamate release, ultimately affecting neurotransmission. The clinical effects specifically relate to this glutamate effect within the nucleus accumbens, which is the center for reinforcement reward and which is greatly implicated in addiction. In a 2012 study by Gray et al., a double-blind trial in cannabis dependent adolescents aged 15 to 21, with 116 participants, randomized patients to eight weeks of NAC at 1,200 milligrams twice daily versus placebo, and both groups additionally received contingency management and counseling. The NAC group had an odds ratio two and a half times the placebo of having a negative UDS, with a confidence interval of 1.1 to 5.2 odds greater. Post-treatment absence rates were not significantly different, however. Self-reported days of cannabis use, as well as cravings, favored the NAC group, although again not statistically significant, and cognitive performance was slightly improved in early treatment-related abstinence in both groups. NAC was found to be well-tolerated. In a 2013 study by Roten et al., a double-blind randomized control trial studied NAC in cannabis dependent patients, specifically looking at cravings ages 15 to 21. All participants were given oral NAC, again at 1,200 milligrams twice daily versus placebo, for eight weeks, as well as brief cessation counseling in both groups. The MCQ, or marijuana craving questionnaire, was used to assess cravings and found no differences between either group. However, published separately by the same authors in 2015, further study analyses did show that NAC was associated with cognitive performance effects via cognitive task performance tests, which was also assessed at weeks 0, 4, and 8 in the same study. The study showed significant improvements in verbal memory, as well as psychomotor speed following marijuana cessation in the NAC group. Data found that abstinence rates in NAC participants was also positively correlated with desire for cannabis use disorder treatment, as well as levels of medication adherence, but inversely associated with impulsivity, as well as baseline urine cannabinoid tests, cannabinoid tests, sorry, suggesting it was inversely related with baseline use. In a 2017 study by Gray et al., a multi-site placebo-controlled trial of 302 adolescents, sorry, adults 18 to 50, with cannabis use disorder was studied comparing 12 weeks of contingency management and NAC, 1,200 milligrams twice daily, versus contingency management alone with placebo. There are no group differences in abstinence rates between NAC and placebo. However, underpowered post hoc analyses did find that young adults in this study, age 18 to 21, had significant differences with the NAC group versus placebo having double the abstinence rates with, sorry, statistically significantly. This does contrast, however, with the significant positive results found in Gray's 2012 study. The adult trial showed that 22% of urine tests in the NAC group versus 22% in placebo were cannabis negative. However, in the adolescent trial 2012 showed that 41% versus 27% were negative. This efficacy may be age-dependent with adolescents, but not adults, thus benefiting at the 1,200 milligram twice daily dosing. The factors may include developmental milestones, socioeconomic situations, family situations, ratio-ethnic disparities, as well as simply the physiologic effects of the 1,200 milligram dosing. Cytopremate has also been studied in adolescents with cannabis use. However, the adverse effects associated with topremate, both within these studies and separate from these studies, are vast and significant, including cognitive and language impair, weight loss, mood effects, electrolyte imbalances, including metabolic acidosis, and a number of significant drug interactions. In 2017, Miranda et al. conducted a double-blind randomized controlled trial of topremate in treatments seeking youth, 16 participants aged 15 to 24, with cannabis use over twice per week, as well as at least one symptom of cannabis use disorder. 80% of the participants did actually meet criteria for DSM-IV-TR cannabis abuse or cannabis dependence, but were not required to meet any of these diagnoses for enrollment in the study. Participants were randomized at two-to-one for six weeks of topremate with motivation enhancement therapy versus placebo and motivational enhancement therapy. MET, or motivation enhancement therapy, is similar to motivation interviewing, but is more action-focused. Topremate was titrated over the four weeks to 200 milligrams per day, and then was maintained at that dose for another two weeks. Topremate was associated with reduced use of cannabis per day at week six, but only of modest effect magnitude, and did not have any improvement in absence rates. Only about 50% of the topremate group actually completed the trial versus 77% of the placebo group. Adverse effects were the most frequently associated reason for withdrawal, and specifically reported use of withdrawal specifically in the topremate group. 42% of the dropout participants reported memory difficulty in the topremate group, but 0% reported this in the placebo group. Adverse effects associated with topremate does suggest there may be limited efficacy in treating cannabis use disorder, but not worth the adverse effects in adolescence. Back to Dr. Stein. All right, for case number three. Here we have a 15-year-old male who presents to your clinic with his grandmother, his guardian, who provides the majority of the history. She explains that her grandson is, quote, on the road to following my son and his wife. They got mixed up in drugs and are still stuck in that world. She says that the patient has a history of ODD and ADHD that was never treated. About six months ago, the patient found himself in legal trouble after a physical altercation with a police officer who found him smoking marijuana. He spent a month in juvenile detention. Grandmother explains that he has always had difficulty with behaviors and is not listening. His school performance was always average, but his grades have been worsening. She notes that he has not been doing the activities that he used to enjoy and has been less interested in hanging out with his old friends. The patient readily admits that he has been smoking marijuana for the last two years. He explains that, quote, I just feel normal with it. He says he has easy access from multiple sources to get it anytime he wants. He says he is now smoking daily. He says it used to be fun with a few friends, but now he does not find it fun, but he feels cravings and has tried to slow down before without success. His grandmother is appropriately concerned for the patient and wonders if there's a medication that could treat ADHD and address his cannabis abuse. What would you tell her? So his grandmother felt that that the patient needed treatment for ADHD, and having had a lengthy discussion of many options we use to treat ADHD, she focused in on bupropion as she was aware that it can help individuals with nicotine cessation in addition to ADHD. After discussing risk, benefits, side effects, and alternatives again, the patient was started on bupropion XL 150 milligrams daily. At his follow-up four weeks later, his grandmother reported that the patient had an okay month, but they weren't really sure if there were any changes. The patient said he didn't feel like it was any easier to concentrate in school and denied any difference in his cravings. His grandmother mentioned that he has been suspended again since the last appointment as he was caught with a marijuana cartridge at school. What would you consider next? Probably not doing that as a repeat option. The grandmother and the patient are both frustrated. Grandmother expressed interest in a stimulant to treat both impulsivity and concentration deficits appropriately. Unfortunately, due to a clinic policy, this was not an option as patient continued to have a UDS that was positive for cannabinoids. The grandmother and the patient elected to discontinue bupropion due to minimal efficacy, and the grandmother is interested in using only one medication at a time. They remember that NAC was discussed at the initial evaluation as another possible option to aid in cessation of cannabis use. The patient was started on NAC 1200 milligrams twice a day. At subsequent appointments, the patient had reduced cannabis usage, grades started to improve, and he has not been suspended again since the last time. There are some considerations to think about in general. In this case, the patient mentioned getting his cannabis from multiple sources. Contamination is something to be mindful of. Could the cannabis be contaminated or laced with anything? Our public health office in Dayton has heard anecdotes of cases of fentanyl-laced cannabis, but we have zero verified reports of this. But it is something to keep in mind as we do keep hearing about cannabis being laced with different things. Another consideration, would therapy be helpful, and what type would you consider recommending? Well, obviously this talk is pharmacologically heavy. I do want to make sure that we stress the importance of therapy, and specifically in this case, or in cases of substance abuse, motivational interviewing. My own experience has been that I've had so much more success treating substance use disorders when motivational interviewing has been a factor. So who's heading over to the motivational interviewing seminar with me right now? Just kidding. Okay, closing remarks. So actually, yeah, before we move on to closing remarks and that sort of thing, we actually wanted to turn it around to the audience. Like I mentioned, I'm an adult psychiatrist. I do treat, and also addiction specialist. My experience is with adults, and like I said, with the Ohio Department of Mental Health and Addiction Services, my employer, looking at the data, an overwhelming majority of our patients that we treat began using, like I mentioned, as adolescents. So I really wanted to turn, that was the whole motivation for this talk today, is to help educate me, to help me understand my patients better, and what options that maybe their family members, their children might have. So we really wanted to take this moment to just turn it around to you guys, and we wanted to hear your words of wisdom, or any experiences you might have had treating adolescents with addiction. So I'm a child psychiatrist, and I'm also an adult psychiatry exposure. I'm running the emergency rooms, so basically for children. Children, usually when they get involved in this matter, it's a lot more serious than that, and I educate the parents, and I ask them for a residential program. I ask them inpatient rehabilitation, not a self-sustaining or non-developmental attraction. It's not working. So that's why I admit them inpatient programs and residential programs, long-term, not, okay, 30 days they are going to go home. No, not. Come back home, do it again. And also I recommend change friends, change school, change the environment completely. I was just going to point out that you're speaking to that peer influence and the importance of that. That was mentioned in some of the studies. So a couple of things here. One, as treatment professionals, remembering that we can start smart recovery groups, which can be great for kiddos. A lot of times we direct them to AA or NA, and it's not a good fit. You do not need to be in recovery to start a smart recovery group in your community, so that's a good option, or at least maybe champion some local leader to get one going for the kiddos. Also, these are tough cases. That second vignette, that second case you discussed especially, right? I mean, I could already imagine there's going to be trauma, eating disorder. If we just look, and I think for us, just knowing what to look for, because a lot of times the pediatricians do not, that if we have a substance use disorder, you know, 30% of our female patients will also have an eating disorder. 95 to 99% will have trauma. The majority of that is sexual assault. And so just kind of just going down that diagnostic line. The other one thing I'd like to know is, working with pediatricians in my hospital, I don't understand why we're not just doing drug testing with kids that are 12 and older. Just seeing the statistics and how preventable these things are, we're not treating this like other diseases to say you're at risk for this, I'm going to test you and then treat you if I find this marker, where we could do cotinine testings and find out if somebody's vaping, because the kids aren't telling us the truth in the pediatrician's office. And I'd love to know your thoughts on that, or maybe how to navigate that. Yeah, that's a great point. I think you need to screen more often. I do think talking with children and adolescents alone and developing a relationship with them without their parents in the room is really helpful at times. They might be more honest about that, but I think you make a great point about the drug testing and kind of advocating for that and practicing it in our own practices and kind of reaching out to the community as well. Does anyone work in a setting where that's done? You know, where you are, kind of, kids are coming in, you know, there's a problem and you are doing those sorts of drug testing just off the bat. Is there anyone whose practice model or setting supports that? Yeah, so for those of you that weren't able to hear, so of course in the emergency room setting, right, that's a place where that's pretty common, right? It's pretty standard for us to DEDS and that sort of thing. Hi, thanks so much for the great presentation. I was curious if there was perhaps a little bit outside the scope of the presentation, but is there any data that you're aware of for specific therapy modalities or behavioral techniques such as contingency management for any kind of SUDs discussed? I think contingency management has one of the strongest evidence bases for substance use disorders, which would, I don't know of specific studies about adolescents in particular, but extrapolating from adults, I think that would be kind of the most useful. I would also just point out the need to treat these co-occurring and comorbid disorders that we've kind of been talking about with whatever modalities is supported for those, whether that's trauma or depression or anxiety or ADHD. I have found that a lot of these kids are self-medicating in a way, and I think whether it's therapy or pharmacotherapy for those co-occurring disorders, that's really important as well. So I work in a local county mental health office, but as a fellow, I worked Monday mornings just doing evaluations, not doing treatment, but I'd sit for four hours on a Monday morning with a kid in the detention center, and this was over the course of about six months in the beginning of my training, and a pattern that I noticed was that there was a lot of early substance abuse in kiddos that ended up in detention, exposures to substances as young as age six, and a lot of it coming from just really poor quality home life, and so I feel like the detention system where the juvenile department probably has access to a special population and could be a source of intervention for those kiddos. Do you have a mental health court or a treatment court in your area? So I'm not involved in the juvenile department. That was just my experience in training. We have two clinicians in my clinic who are therapists that actually go and do like safety assessments at the juvenile departments in the detention center. But I don't know to what extent those kids actually get connected to services. The fellows that go make recommendations, and then that, my understanding is there's a release for the attorney to decide what to do with that evaluation and information, and sometimes those kids get into treatment with our local A&E department, but I imagine there are a lot of kids that fall through the cracks. Yeah. Unfortunately, I think the legal system is often the way that kids or adults get in, unfortunately or fortunately, I guess, get into treatment. I think if there's a good mental health court or a treatment court that really advocates for that, that's a really awesome step to get into treatment that way. But it's unfortunate that they have to rack up maybe legal charges before that can happen. Just one more pearl I'll share. Sometimes it can be painful to do the whole schmoozy touring centers things, but these really expensive centers, a lot of them, if you have a good relationship with them, and you have a special case where, again, I'm going back to that 18-year-old, right? They have room for those patients because they need enough people in their programs to run the programming. So even though they might be $50,000 a month, they will often offer free treatment. And if you have a good relationship with the intake coordinator, and you talk to your patient and say, look, you're gonna be on a strict contract, these centers are always just looking for more people to have there so they can run good programming. If they only have a couple of people there, they can't run good programs. And I think that that's not something that's talked about. I don't think that they freely just share this information, but just know that that's done. And another thing that you can do kind of just to outreach as a provider. Yeah, these cases aren't necessarily complicated medically, right? We kind of know what we can use for treatment, and we can find the evidence for that. Child and adolescent psychiatry, we're pretty comfortable with off-label use of things because that's pretty much what we do. It's the other factors, the comorbidities and the psychosocial situations that make them really complicated. So for those of you that might not be using that with your child and adolescent population, do any of you see yourselves using that or being supported by your entities or wherever your practices are? Is this something you'd consider? And if not, why? And what kind of barriers do you think you face? So I'll start us off. I think certainly stigma, right? Even in one of the vignettes, well, can't you just treat them for the depression, right? And I think it's so unique as psychiatrists. Of course we know mental health in general, there's so much stigma. But we're finding these parents saying, well, treat the mental, no, they're mentally ill, or treat that. It's almost like that stigma with addiction is greater. And so I think that's something that we need to be aware of is that stigma with addiction is greater, right? Than the general mental health issue, so. Great, does anyone have any questions? Anything you'd like to discuss further? I'll ask something. I'm an adult psychiatrist and I've been at the VA for almost a decade, so I haven't seen a teenager in a while, but I see a lot of young adults. We've been doing a lot of alcohol pharmacotherapy, but definitely stigma and a lot of the PCPs not wanting to do it and push back. And I mean, that happens. But I was curious in terms of, I know you said a lot of things are off-label in kids and teens, but I know with my adult patients, like if there's not buy-in, we'll do what you all talked about, start an SSRI. And then they come back and like, they're like, maybe I will try naltrexone. But I didn't know how the data is for that in terms. I know when I was in training, sometimes they would say, well, don't even start an SSRI. They need to get sober first, but I think that's kind of fallen out of favor. So I don't know for kids and teens, if you always approach it as just start the SSRI or if you have different opinions about that, if they're heavily using. Yeah, we're not necessarily aware of any data, but I do like you if I will start the treatment that they will buy into. So if they buy into the SSRI for depression, let's start there. And if they buy into both treatments, I may not start them on the same day. I might stagger it a little bit, but let's start the SSRI and naltrexone, you know, a week apart or two weeks apart or something. Because I think treating both is the most important. And I agree, I think it's, I've had training and teaching that says, don't even bother starting the SSRI until you get the substance use treatment going. But I'm like you, I think that's fallen out of favor. Well, thank you for everyone for sharing your experiences and all that, so. Martha? Yeah, thank you so much. And hope you have a good rest of your evening. We're available here if anyone wants to chat further.

adolescents

substance use disorders

evidence-based strategies

medication-assisted treatment

opioids

pharmacotherapy

psychosocial support

buprenorphine

naltrexone

stigma

mental health