Well, hello, everybody. Hello, everybody. My name is Reed Finlayson. I'm an addiction psychiatrist here at Vanderbilt University. I'm delighted to be sharing the screen with Dr. Nasheen Hossain, who is a pharmacist at Vanderbilt. We work closely together. And I'm excited to be speaking to pharmacists. I'm old enough that I remember the days when pharmacists and doctors used to work very closely together. And it seems to me that we've drifted apart. In my view, it's created some problems for us and for the people that we serve. Our presentation today is on the medications that are used for opioid use disorder. We're going to try and go through the slides fairly briefly and give you lots of opportunity to ask us questions. But to begin with, I have to acknowledge that this presentation is sponsored by the Opioid Response Network. STR-TA stands for SAMHSA State Targeted Response Technical Assistance. It's a grant that created an entity called the Opioid Response Network, which is used to educate and train professionals in the country. And the technical assistance is available to support evidence-based prevention, treatment, and recovery from opioid use disorders. The ORN program provides local experienced consultants in the prevention, treatment, and recovery from opioid addiction or opioid use disorder to communities and organizations. They accept requests for training. And each state has a technology transfer specialist, or a TTS, who is expert in fielding calls and organizing programs such as this. This acknowledges the grant from SAMHSA. And the overall mission of the program is to provide training and technical assistance using local experts to enhance the prevention, treatment, and recovery efforts across the country, specifically addressing state and local needs. And today, especially medication-assisted treatment for opioid use disorders, medications like buprenorphine, naltrexone, and methadone. And the approach is to build on existing efforts to enhance, refine, and to fill in gaps when it's needed, at the same time avoiding duplication and not trying to recreate the wheel. So, I want to begin by defining substance use disorders. They're chronic medical conditions characterized by compulsive substance-related behaviors or use and continuing to use in spite of harmful consequences. The disorders involve cycles of remission and recurrence. The disorders disorders have biopsychosocial underpinnings. We know that the genetic contribution, the susceptibility to substance use disorders, involves 40 to 60 percent genetic factors. And there are some environmental factors that are prominent as well, such as trauma, adversity, particularly during childhood, but also in military, and minority stress. People who are subject to discrimination and stigmatization for other reasons are more vulnerable to developing substance use disorders. The statistics are that one in seven people will develop a substance use disorder at some point in their lives. This is not uncommon. And the diagnosis of substance use disorders is a major disorder in DSM-5, the Diagnostic and Statistical Manual of Mental Disorders that is regularly updated by the American Psychiatric Association. There are four main categories of criteria. These are, number one, impaired control, of the use of the substance, taking more substance than was intended. Number two, impairment of social roles, not fulfilling parenting responsibilities, work responsibilities, breaking the laws in public, that sort of thing. Number three is risky use, use that can lead to injury, impairment, or death. And finally, physiological dependence, which I'm sure you're all familiar with the ideas of tolerance and dependence. And of course, withdrawal symptoms when the substance is stopped. We'll talk about that in a moment. So, opioid use disorder can produce changes in the brain. And these are particularly noticeable with severe disorder. The neurocognitive changes include, excuse me, abnormal mood, thought disorder, cognition, and impaired decision making. They can include abnormal reactivity to stressors and environmental cues. They can be associated with cravings which originate in the brain and can be overwhelming. They are characterized by changes in insight and the impaired ability to look after oneself and be healthy or even to be alive. That's how powerful the changes can be in severe opioid disorder. And it is a chronic disorder with the highest mortality of all psychiatric disorders. Now, this graph shows the overdose death rates between 1999 and 2017 that involve opioids by the various types of opioids in the country of the United States of America. There was in 1999, the presence of an increase in opioid prescribing. Many of you will remember the OxyContin crisis that Purdue Pharmacy generated with a lot of consulting about advertising. You'll remember the smiley faces. You'll remember the doctors being criticized for not providing enough opioids for pain and so on. And then the second wave came about really when the states decided that the best way to handle the rise in opioid prescriptions was to shut down the prescribing. And even though that was not medically advised, it happened. And when the supply in the community vanished, there was a rise of an influx of heroin from a variety of sources throughout the country. And then the third wave, of course, was the rise in synthetic opioids, fentanyl and derivatives, now including stimulants and a variety of other agents that are used to cut the fentanyl and and try to make the effect last longer. And what you can see is that the death rate from heroin and prescribed opiates has started to fall, but the alarming rise in deaths from synthetic opioids persists. Now, about 35% of people with opioid use disorders have received some treatment or another, according to Knudsen's work in 2011. 34% of facilities use pharmacotherapy for opioid use disorder, and yet only 10% of patients in the community at large receive any form of pharmacology for opioid treatment. One of the major principles of treating opioid use disorder is that all patients with opioid use disorder should be offered the option of treatment with an FDA-approved and indicated medication. And these medications include buprenorphine, methadone, or long-acting naltrexone. Naltrexone is marketed as Vivitrol and is available in a long-acting injectable form. Evidence-based psychosocial interventions are also used and are very important in combination with the medication to improve outcomes. The goals of using medications for opioid use disorder, number one, to try to reduce mortality. We're, at least in Tennessee, not entirely successful at this point. There's been some minor changes, but we are one of the leading states, probably in the top three or four, in terms of continuing mortality from opioid overdose. We want to, secondly, try to reduce the morbidity associated with opioid use disorder. The intravenous use of drugs transmits viruses. HIV, hepatitis are very common, and other infectious complications from IV drug use, which we see regularly here at our tertiary medical institution at Vanderbilt, where people with blood-borne infections, heart valve problems, septicemia, all kinds of complications from intravenous drug use are managed here. The next goal is to reduce the amount of opioid use in the country. The United States leads the world in terms of opioid consumption. The next is to increase retention in addiction treatment. We're not always successful at once starting medication treatment, in continuing it for a variety of reasons that range from our profit-oriented healthcare system to the availability of drugs and other biopsychosocial supports for patients. We also want to improve the general health and well-being of our country, and to reduce the amount of drug-related crime. And I would remind you that two centuries ago, Dr. Benjamin Rush identified addiction as a problem that doctors should be looking after, not lawyers. And the state that we have now is a terrible epidemic, not only of opioid use disorder, but of gun violence in our country. And the police, although I haven't seen the figures specifically, but the local police tell me that very often the shootings that they look after and investigate have to have as a cause some drug transaction or other. The purpose of the opioid use medications are to reestablish homeostasis in the reward pathways of the brain. These pathways have been disrupted by substance use. Opioid use medications control the symptoms of withdrawal, they suppress cravings, and they restore emotional responsivity and decision-making capability in people who are suffering from severe opioid use disorder. The medications also decrease the reactivity to stress and drug-related cues, they block the reinforcing effects of opioids and prevent relapse, and they promote and facilitate patient engagement in therapy and recovery-oriented activities. So, we're going to turn and look at these drugs in slightly more detail. First of all, methadone is a full-opioid agonist. The advantage of methadone over prescribing regular opioids, such as morphine, to manage addiction, the advantage is that methadone has a longer half-life, and most people can manage with a once-a-day dose. Methadone is cheap, it's available in pill form, dissolved in liquid, and wafer form, and it's usually dosed daily, and it's available under federal regulation through an opioid treatment program. Buprenorphine is a significant advance over using a full agonist, because it's a partial agonist. It is a film base or a pill or tablet that is inserted either under the tongue or inside the cheek. There have been some implants experimented with, they've pretty well fallen out of favor, but there are some injectables that are in early trials and some use, and the law has recently changed so that any prescriber can prescribe a buprenorphine without an appropriate waiver. I've had the waivers for many years, but it is no longer necessary to have the waiver, Dr. Mayfield, to be able to prescribe it. In regards to the waiver, one important piece to note is that the federal regulation has rescinded the data 2000 waivers that providers no longer need that XDEA to prescribe buprenorphine products, but however, dispensing pharmacies, if you are dispensing out of state, you still have to comply with state regulations. If a certain state still requires the waiver, then you have to make sure that that provider has an XDEA. The state of Tennessee does not require the waiver and is in line with federal regulations, but just one key point I wanted to clarify. I want to excuse my bad manners. I meant to introduce my partner in this presentation. Please join in at any time. I can start on the next one. Yeah, that would be perfect. Just a continuation about the pharmacology around the medications for opioid use disorder. They're largely categorized in terms of their agonism or antagonism. You'll look here on the graph depicted. Methadone is our medication that has full agonism. As you increase the drug dose, you will increase intrinsic activity at the mu opioid receptor. Buprenorphine is our partial agonist. You'll get what's called a ceiling effect. As you increase the dose, and its literature cites around 24 milligrams per day, that you will get a ceiling effect. You will have blockade of that receptor, but you will not reach euphoria with a ceiling effect on buprenorphine. Then naltrexone, which is an absolute antagonist, so it binds and it has a larger, a stronger affinity. All of these medications, mind you, have a stronger affinity for the mu receptor than natural opioids and fentanyl and other opioids like oxycodone. That's also important to note. This is a picture graphic of what we're talking about. For methadone, it binds to the receptor completely and has full agonism. It will induce the intrinsic activity of a mu receptor and all of the downstream effects. However, it will have a delayed onset, and so you're not getting that immediate euphoria like you would if a patient were to ingest an opioid. Buprenorphine, this does have agonism, but it's a partial agonism. This depicts what we mentioned about a ceiling effect. Basically, over doses of 24 milligrams per day, you will not reach any additive effects, and you won't be able to reach euphoria. With naltrexone, picture it like a corkscrew. It's complete blockade. It's an antagonist at the mu receptor and stops any downstream effects from that receptor. In terms of efficacy, when we compare the number of patients that remain in treatment versus the control group, you can see that the buprenorphine group largely remains in therapy when compared to controls who have no buprenorphine therapy. And with methadone, similarly, if you compare the methadone group versus the control, the percent of patients that have a positive urine drug screen for opioids is significantly higher in our control group. So for both graphs, it shows you that buprenorphine and methadone are efficacious. And in terms of dosing, this was a question that came up as well. So this is a general guideline, but for less than 40 milligrams of methadone, we're targeting the management of withdrawal symptoms and greater than 40 milligrams per day, we're targeting the cessation of opioid cravings. And in general, doses less than 50 milligrams, you can kind of put in a bucket for pain and greater than will be for opioid use disorder. But I remember when we talked to Dr. Finlayson that you mentioned that you wanted to share that this guideline of 50 was largely arbitrary and can be used as a general guideline in terms of how you're categorizing these prescriptions. And then, so in terms of the limitation of agonist therapy, so in particular methadone and buprenorphine, these require a significant amount of oversight, more so for methadone, you have to be a licensed dispensary in order to provide methadone for opioid use disorder, but not for pain. So a regular pharmacy can dispense methadone if it's not used for opioid use disorder. And then also for side effects, buprenorphine is a bit safer because of its sealing effect and also the combination product of suboxone, which has naloxone combined, that also prevents euphoria if it's misused or diverted in terms of IV usage. There's a risk of misuse and diversion and of course safety issues as well. And then for antagonist therapy, the naltrexone, while it does prevent opioid receptors, it's meant to stabilize the patient's system functioning while it blocks exogenous opioids and the redevelopment of physical cravings. The main limitation here is that a patient has to be completely opioid night free for five to 10 days, depending on the formulation of whether you're doing PO naltrexone or the injectable Vivitrol. And so as you may be aware, this can be difficult for a lot of patients to start naltrexone. However, in head-to-head trials with buprenorphine and naltrexone, they were both equally efficacious in preventing relapse. The limitation is starting naltrexone and having that up to 10 days of opioid-free time is difficult for our patients. And then I'll pass it over to Dr. Finlayson. You know, one of the major blockages in terms of helping people with opioid use disorder is stigma. And stigma originated a century ago with the Confusion and the Harrison Act. I'm not gonna go into a whole lot of historical detail, but for the last century, we've contradicted Dr. Benjamin Rush, who was formerly considered the father of American psychiatry and lauded for his work in addiction, primarily to alcohol in his day. So stigma has developed because physicians were not allowed to treat addiction with medication. And people, many physicians have been prosecuted for trying to help the suffering of their patients over the last century. And the sufferers have, the sufferers or the people who have opioid addiction are largely banished in the criminal justice system and not offered as much help as the people in the community. The pursuit of drug prohibition has generated a parallel economy that criminal networks operate. And the solution to that is to treat opioid use disorder and have the demand go down in our streets instead of continuing to go up as it is today. The criminal networks resort to violence to protect their markets. And I already mentioned that the current stigmatization of addiction leads to a lot of violence, theft, and murder in the streets. And our police and our military and other forces pursue the drug dealers and the drug importers and contribute to the violence and the insecurity in our communities. So stigma has many forms. Stigma, the worst type of stigma, of course, is self-stigma where the addict blames themselves. They feel hopeless. They mostly don't realize that it's an illness. They believe that they made a choice to start using the substance and therefore they blame themselves. And really not everybody who starts alcohol or drugs is susceptible to getting a full-blown addiction. And the stigma also affects the recovery community because there's so much emphasis rather on becoming abstinent as in Alcoholics Anonymous or in drug treatment support groups that insist on abstinence as the end point. Stigma also comes from people in the community who see it not as a disease, but as a moral failing. If you would just pull yourself up by your own bootstraps and stop using it, it would go away. But it doesn't go away. And we know from painful experience that the worst kind of withdrawals do not lead to less use, but to more. And many clinicians are ignorant about the disease of addiction and still believe that treatment is ineffective. The worst comes from the support groups who say, you're just exchanging one drug for another. That is a stigmatization of drug treatment and recovery. It's important to think about the terms that we use when we talk about substance use disorders. The stigmatization can prejudice and produce discrimination. We want to avoid words like addict, abuser, junkie, user, and instead talk about a person who has a problem with substance use disorder. We wanna try and avoid the terms clean or dirty. And we try to use the terms negative, positive, abstinent, substance-free, actively using, or the words like a habit or a drug habit. These terms suggest that it isn't a medical problem. It's just a matter of willpower. And we know that many people with advanced substance use disorder are unable to stop the habitual behavior. And then finally, opioid replacement or methadone maintenance are a subtle language to suggest that they're not quite normal. They're not, you know, we prefer to the terms medical medication-assisted treatment or medication for opioid use disorder instead of replacement or maintenance. Now, stigma erodes confidence that opioid use disorder is a valid and treatable medical condition. It creates barriers to jobs, to housings, to relationships, to parenting. It deters the public from wanting to pay for treatment. And you know, because we exist in a for-profit healthcare system that the insurers want to make sure that they keep most of the money that people pay for healthcare insurance, especially if they can get away with it because the people are too stigmatized to speak up about it. It allows insurers to restrict coverage, which we deal with here at Vanderbilt every single day, trying to find ongoing help and support for the people that we treat here. It stops people from seeking help and it impacts clinical care and treatment decisions. Stigmatization is insidious. It can be a belief, it could be a value, it can be an attitude. It leads to prejudice, it leads to discrimination. And the language itself is a bridge or a barrier in the fight against stigma. So what can you do? Perform a language audit of the existing materials that you use to interact with patients that you're serving. And look out for language that might be stigmatizing and replace it with more inclusive language. Look on your electronic documents, search for the word addict and replace that with person with a substance use disorder or search for abuse and replace it with use or misuse. And make sure to review both internal documents, your mission statements, policies, as well as external ones, the brochures or any forms that you use interacting with patients that you're working with. So in a scoping review of factors that influence opioid overdose prevention in people who are involved with justice, people who are in court, in drug court, in jail or in prison, only one in four or 25% of individuals who are recognized as having an opioid use disorder and are involved with the criminal justice system get any sort of help during the course of a year. People who are leaving prison have fear that they're more likely to get rearrested. Expanded partnerships can help with this. And the suggestion is that we integrate mental health services, addiction services and correction services in the state, in order to overcome the epidemic of opioid overuse deaths. Chirian and his colleagues in New York City this year published this paper showing a lower risk of non-fatal overdose epidemic, sorry, overdose deaths within two weeks of release from jail. The people who were surveyed were 8,860 individuals associated with incarceration. And when they left, they were able to analyze 10,000 similar individuals. And what they found was that within 14 days of jail, there were less overdose deaths. And where they found no difference at all was after that first 14 days. So this emphasizes that treatment has to be continuous and is not an event. The ways that a drug prohibition contributes to overdose deaths is that we're unable to control the adulterants, the other chemicals that are put in unregulated illegal markets. People with substance use disorders are overrepresented in prisons. And the people that most need the care can't afford to get it. There's no specific treatment designed for females, although they have special needs because of behaviors and pregnancy. And we know that defoliant sprays can protect, or sorry, can create health hazards, but we don't prohibit the adulteration of drugs. The Lancet Committee, sorry, the Lancet Journal, a very famous international health journal, has published a public health and international drug policy identifying the paradox that suppression of drug use, prohibition is portrayed and defended vigorously as absolutely necessary to public health and safety, but it is not. The evidence suggests that drug suppression and prohibition actually contributes to lethal violence, to disease transmission, to discrimination, to unnecessary pain, and undermines the rights to health. What is recommended internationally is increased decriminalization of minor nonviolent drug offenses. We need to reduce violence, phase out the military and police tactics, improve access to harm reduction services, reject compulsory detention and abuse. Throwing people in jail doesn't work. Treating people in hospital can, or providing adequate assessment and intervention within the correction service can. We need better care for HIV, HCV, or hepatitis, and tuberculosis, along with venereal diseases, which are rampant among intravenous drug users and spread to the rest of the population. We need better access to drugs for treatment, the very drugs that we're talking about today, and better care for females. If I can go over this slide. So there's a few training opportunities outside of this session that are available to clinicians. The hyperlink here, PCSSnow.org, is a really, really great resource. They have, it's all free. You can even get pharmacist CE credit. They have typically one hour long sessions, and they have a large repository of lectures available to you on various subjects relating to substance use disorders. So this is a great resource to have in your back pocket. And that's the conclusion of our presentation. Yes, at any time you can call, email, or visit theopioidresponsenetwork.org for follow-up. But we have a few minutes now. If anyone has questions that you'd like Dr. Hussain and myself to attempt to answer, we'd be happy to entertain them. All right, thank you so much for your time. I do have a, well, we have one question is, you mentioned during the presentation states that may require an XDEA. We weren't aware of any. Do you know of some off top, or? I don't, I just wanted to make sure, because you mentioned that you mail outside of states. I just wanted to make sure that that distinction was, that although it's a federal ruling that the XDEA is no longer, it's rescinded, you just have to be mindful of state regulations. I know Tennessee doesn't, but I wanted to make that aware. Okay, any other questions? I think also, Jade, one thing we didn't touch on, but I wanted to really quickly in your initial emails was the difference between MAT, MAT, and MOUD. And the short answer is there's really no difference. So MAT, medication-assisted therapy, and MOUD, medications for opioid use disorder, are essentially the same thing and can be used interchangeably. Yeah, so it's all kind of new to us. So we're, I thank you so much for this general overview of everything, and there's no more questions. Okay, thank you guys for putting in the time and effort in presenting this to us. It's really helpful for us to have better knowledge of MAT and MOUD and all the differences in kind of what our country is facing right now. So thank you so much. Thank you guys. And if there's any questions that come up, we're available as well. Absolutely, thanks very much, Jade. Awesome, thank you. Have a great day. Bye-bye.

opioid use disorder

buprenorphine

methadone

naltrexone

stigma

inclusive language

opioid crisis