Hello, my name is Dr. Derek Glenn. I'm here to have a conversation with you about medication for opioid use disorder, MAUD. I have no financial relationship with any commercial interests related to the content of this presentation, and I will not be discussing off-label use during this presentation. Medication access and training expansion at MATE requires a one-time eight-hour training and evaluation, treatment, and management of substance use disorder for all new providers applying for a DEA license. This presentation can be applied to that eight-hour content. The objective of this presentation, overview of medications used in MAUD, what we describe the clinical opioid withdrawal scores, CALS, we will describe the treatment for withdrawal symptoms, and we will understand patient flow with buprenorphine. Currently there is a huge treatment gap. Of those that need treatment, it is severely not ordered. Those that received treatment are likely not to get that treatment. As you can see from this particular study, one in four people received treatment, and those that did receive medication were less likely to drop out. To that treatment gap related to the huge opioid overdose, it allows those that need that medication to get the needed medication, the FDA-approved medication, buprenorphine, methadone, and naltrexone. You can see that if you had received that needed medication, you were more likely to stay consistent and persistent on treatment. Addiction and recovery is a continuous process. As you can see, addiction is a chronic condition, but the bridge between addiction and recovery is the needed medication for opioid use disorder. That is a point that can bridge the gap for recovery. The national drug-involved overdose deaths is the epidemic proportion. You can see in this graph that among ages from 1999 to 2019, there was huge tremendous death involving fentanyl primarily, synthetic opioids, followed by psychostimulus, followed by cocaine, prescription opioids, benzodiazepines, and antidepressants. Addressing this overdose death, which is a national problem, with the needed treatment, the treatment gap is those that there's more people that need treatment than the medicine that is available for providers to prescribe them. Mod medication, again, it's approved by the FDA, Food and Drug Administration. They consist of methadone, buprenorphine, and naltrexone. Neurobiologically is the mechanism in which how mod impacts. It relieves the psychological symptoms and withdrawals. It relieves the cravings, and it blocks the urophoric effect of the opioid that is abused. How the medicines work, methadone is a full agonist. Again, it tightly attaches to the opioid receptor. Buprenorphine is a partial agonist, and it activates the receptor to a lesser extent. However, it has a tremendous affinity for the mu receptor. And oftentimes, if opioid is attached to it, it will uncleave the opioid and it'll attach to it. And that's the mechanism of that, how it works. And what happens oftentimes is what's called a precipitous withdrawal. Now, naltrexone is an antagonist, and it completely blocks the effects of opioids. And we'll discuss all these medications further in this presentation. But I think it's important that we understand the neurobiological impact and how these medication help the opioid use disorder patient go on to the road of recovery. Methadone in the early stages, what's interesting is Dr. Dole in his medical treatment for heroin addiction clinical trial with methadone in 1965 found that a group of these medications, this methadone, that for heroin addicts, it caused them to have less craving. It caused them to be stabilized, which was great because it allowed them to work. It allowed them to get reacquainted with their family. And this treatment required you to be supervised. But it was a tremendous gap to help out, to assist patients that had these addictions. Methadone early days continue. Again, a narcotic blockade. Methadone is a way that we can stabilize the patient in a state normal function. It blocks the treatment. A single daily dose of methadone prevents one from feeling symptoms of abstinence, sick, and euphoria. So it stabilized the patient that is addicted to opioids or heroin or fentanyl in a way that allows them to have a stable life or function, work daily, stabilize with their family. And it's a tremendous gap that we can bridge for our patients. Overview of methadone. It's appropriate for patients physiologically dependent and meets federal criteria for opioid treatment programs admissions. It reduces withdrawals and cravings. It blunts or blocks illicit opioid euphoric effect. Doses will start low. Overdose is a risk because it is an abusive drug. But it's a risk during only the first two weeks, especially with polysubstance use such as benzodiazepines or alcohol use. And after stopping methadone, all methadone is taken daily. So when one has opioid use disorder and they decide to go for that treatment bridge of methadone, they usually have to go to an opioid treatment facility early in the morning and they get the medication on a daily basis. Prescribers only SAMHSA certified opioid treatment facilities can administer or prescribe methadone. Restrictions are required. And again, they're only OTPs that are federally certified can dispense methadone for OED. Some exceptions for additional provisions of methadone or buprenorphine are allowed. Recently within the COVID, with over COVID, with methadone, if you were stabilized, it allowed for like a 28-day supply of methadone. As you can see, this is an example of a patient that would go to opioid treatment facility program and get their medication in the morning and then go on to their daily activities or work or whatever function they would be doing that day. And so this would be their routine of how they function. Buprenorphine is the other drug that we'll overview. It's appropriate for patients that are psychological dependent. It reduces withdrawal and craving. It blunts or blocks illicit opioids, euphoric effect. Remember we said that buprenorphine has a partial agonist. So again, it has such a high affinity for the immune receptor, it will block any other opioids from coming at it. It is for patient education. It's for patients that are in opiate withdrawal, is required to receive the first dose. Oftentimes they're required to be in mild to moderate opiate withdrawal. We'll go over the cows in a bit. It's a risk for patients that are on other polysubstances such as benzodiazepines or alcohol or after injection or stopping buprenorphine. How is it administered? It can be given sublingually, if taken daily. It could be actually given extended relief, form of injecting monthly. It can be prescribed by your doctor, your nurse practitioner, your physician assistants, as well as other advanced practice providers. There is no waiver required right now for administering buprenorphine. Again, it is a requirement for eight-hour DEA training on mechanisms and administration for substance use disorder. And again, restrictions and requirements, individuals practice with DEA registration no longer require specific X waivers. OTPs, opioid treatment programs can dispense buprenorphine. Oftentimes they're given at an office base. Pharmacologic, it's the first med FDA approved that allowed office-based treatment for opiate use disorder. It's a Schedule III controlled substance. Again, we talked about it's a partial agonist at the immune receptor. But it has such a high affinity for the medication, for the immune receptor. It has a half-life of 24 to 42 hours. It can be displaced full opiate agonists such as oxycodone, heroin, methadone, and fentanyl. So that's why one would have that precipitous withdrawal if they were addicted to one of these full agonists. It has a sealing effect. And we'll describe that in a bit. But it voids the adenine respiratory depression that is associated with a full agonist. And a lot of times for opioid overdose, which is a huge issue. You can see here how a full agonist heroin, so one that was on methadone and heroin, and it has a full agonist, it does not have a sealing. And so that's where we have the tremendous abuse and respiratory depression, opioid death that can occur with these full agonists. Again, with the partial agonist, buprenorphine, which is considered the gold standard for treatment, it has a sealing effect. So there's a limited respiratory depression. There's a safety profile. It's a limited euphoric effect. And patients can limit intake. So buprenorphine profile really allows for safety, it allows for persistence of treatment, it allows for less respiratory depression because that's a huge factor in which has caused an opioid overdose is people take the medication and they overdose because of the respiratory depression effect. Mortality risk during and after opioid substitute treatment, systematic review, and meta-analysis of cohort studies. So in here, this study by Serto talked about 19 cohorts that were on methadone and buprenorphine. The objective was to compare the risk of all causes of overdose mortality and patients who overdose on MOD in and out of treatment. The MOD included methadone and buprenorphine. It concluded that over 1,000 persons years in treatment burst out of treatment. And we can see that the overdose for all causes was 11.3 versus 36.1. The overdose was 26 verse 12.7. So in treatment, again, the people that are in treatment that are able to sustain really reduces mortality of overdose. Again, the retention in methadone and buprenorphine treatment is associated with substantial reduction and the risk of all cause of overdose mortality. So being on these medications for somebody that is addicted to opioids, addicted to fentanyl, addicted to heroin is crucial because it allows them to have to reduce their risk of overdose and reduce the risk of mortality. So that's the big picture here. And buprenorphine comes in a variety of different forms. Comes in sublingual tablets, generic names, subazole, and this is buprenorphine and naloxone. And what's interesting with these combined medications, the naloxone is pretty much irreverent unless it's injected the wrong way and that it will, again, prevent them from going and getting high. So the naloxone, it creates an additional safety profile for buprenorphine that prevents abuse. Again, these tablets are sublingual. Buprenorphine comes as a subtext, it's buprenorphine by itself, but the film, the buckle film has the combined naloxone, which increases the safety profile of buprenorphine because a lot of times with these medications or methadone, there's an abuse, there's a situation where they go ahead and administer this medication to others or they sell it on the market. So this kind of prevents with naloxone, it prevents them from the misuse of the needed medication. It also comes in the buckle films, the subdermal implants. The transdomal buprenorphine is used for pain management, chronic pain, and again it comes in injectable formulas. So this these are the different types of buprenorphine that help out with not only pain management but people that are addicted to opioids. Now for anesthesia providers this is a clinical pearl take-home point. Recommended for post-operative management. Oftentimes the continuum for elective, urgent, or emergent cases. The anesthesia provider needs to know how to manage a patient that might be on buprenorphine. Again if it's buprenorphine management and they're mild to moderate pain, they could take a home buprenorphine dose can be split into two per day. Those doses prevent an analgesic effect. So splitting those doses. Severe pain, one must consider home buprenorphine can be split into three times per day. Consider increasing dose of buprenorphine to 24 to 32 given divided doses. Consider close monitoring if increased or adding opioid for pain. In a situation where you have acute pain with other opioids, you want to maximize the non-opioid strategies. You want to treat the acute pain and the high affinity additional opioids as indicated in patients with opiate use disorder. You want to avoid opiates that the past might have misused. So if they misuse fentanyl in the past, we might want to avoid that. So any fentanyl derivative hydromorphone likely will be the best, the most effective due to high receptor affinity. Consider close monitoring increasing the added opiate for pain. And we have to think about, we have to consider a multimodal approach. Multimodal meaning using regional, neuraxial, these are our other gabapentin, opramib. These are mechanisms that will create a multimodal approach to attacking those receptors. That non-opioid pharmacology a lot of times using the ERAS protocol, opioid sparing, regional anesthesia, epidural catheters, TAP blocks, peripheral nerve blocks, again with and without catheters. We want to do local infiltrates by surgeon. If they're, you know, if they're having surgery and they're on buprenorphine, these are ways that we can consider. Dexamethatomidine, Presidex for sedation, topical agents such as ice, lidocaine, NSAIDs, catorolac, opramib, antineuropathic agents when indicated, relaxants. These are, these are medications that we have in our arsenal as anesthesia providers that can help in multi, the multimodal attack. Non-pharmacological management such as ice, surgical site position changes, using peer recovery support, understanding that 12-step utilizing narcotic anonymous. These are other peer support or behavior support that can be very beneficial for the recovery. And post-op disposition in the PACU. These patients, you know, if somebody's in pain and say they had a knee arthroscopy or knee arthroplasty, then they're in severe pain. That's going to limit their mobility. It's going to limit their recovery and their length of stay is going to be increased. So optimizing these patients and having a strategic plan to attack in their PAM before they have surgery is the key. Again, we want to discharge them home in good pain control. We want to anticipate any kind of social determinants of health factors, any, if they have steps or they have any transportation issues to make sure they get to their medication. Naltrexone. Naltrexone is, again we talked about, it's a complete opioid agonist. Appropriate patients, patients must be abstained from short-acting opiates for at least 7 to 10 days or longer. Acting opiates for 10 to 14 days. It's blocks illicit opiates completely from UFO effect. So it, patients that are on naloxone, naltrexone, it, if somebody is taking this medication, it's going to completely block the effect. So it's a, it's a great mechanism for somebody that has been committed to say they're not going to do this drug. Patient education needs to be opioid free for 7-10 days. So they have to understand that this is not a medication that you can continually use. Overdose is a risk after stopping. Again, once one knows that they're on this, they know that if they take any medication, they're going to have, it's going to, it's not going to give them that urethoric effect. So it's a, so somebody that's committed to recovery. It can be prescribed by MDs, MPs or PAs and can be administered or prescribed by extended release to qualify healthcare professionals. Restrictions are required. No specific regulation are required. Narcan. Narcan is now available over the counter. So it's a tremendous safety mechanism. So somebody that might have overdosed, Narcan is something that any family member, any healthcare provider, if they see somebody that's overdosed or know somebody that has a history of overdose, they can administer this and get them the needed treatment and help that they need. Vivitol. Again, this is naloxone, naltrexone. Now the clinical opiate withdrawal score, CALS, it is how one assesses someone to get on buprenorphine, somebody that is a withdrawal, somebody that was witnessed or somebody that caused EMS and they noticed that a person has overdosed on the medication. And so what this does, it assesses the withdrawal symptoms, assesses the pulse rate, it assesses sweating, it assesses where you're restless, your pupil size, whether your bones or joints are aching, where you're running nose or tearing, you have GI upset, tremors, vomiting. And the score ranges from 0 to 47. So withdrawals are mild to moderate. I think I talked earlier, most of the time people will dose buprenorphine with a mild or moderate withdrawals. If you're severe withdrawals, it's 25 to 36. So that when you're in severe withdrawals, you might get also other adjunct medications to help out with the symptoms, withdrawal symptoms. And again, severe is greater than 36. This right here is a diagram and it shows someone that comes in withdrawal symptoms to the emergency room and their screen. Positive screening for drug overdose, that might be a urinalysis or a blood test. Oftentimes the withdrawal assessment is a subjective or using the clinical opiate withdrawal score to see what is the withdrawal severity. Again, the active withdrawals, they can go into treatment, treatment referrals such as methadone or buprenorphine. And so being patient-centered, listening to the patient, giving the patient options is a way that we can attack and help the patient move from addiction to recovery. Again, that slide that we are bridging the gap, that's exactly what we're doing. Withdrawal symptoms management. Again, when we have withdrawals, we're gonna have high blood pressure, we're gonna have GI, we're gonna have pain. Those instances that we talked about on the cows, what's going on, we want to have medications that are treating those symptoms. If it's high, if it's an increased heart rate or increased blood pressure, clonidine is a great drug. GIs, we want to, if they're having diarrhea, we want to, or having vomiting, adenositron or reglan, pain, you know gabapentin, Tylenol, NSAIDs. So these are medicines that we can use multimodally to help out that patient, mitigate and navigate through the withdrawal symptoms while we're getting them the needed mod treatment such as methadone or buprenorphine. Now let me take you through a patient flow with buprenorphine. The initiation, patient presents to the treatment self or provide a referral. So in the scenario where oftentimes the patient comes to the ER, they are given, say they might be prescribed buprenorphine, but then they refer them to the to the opioid treatment program. And so they're they're going to this facility and they are getting referred. They're given the resources. They're again screened, more likely by cows. Assess whether buprenorphine is appropriate for them. Again, they're given a decision point. That decision point is saying, hey, would you like methadone, a medicine that you have to come here every day, or would you have like buprenorphine, which gives you a little bit more flexibility. You want to intake the assessment. So they're gonna do a thorough assessment. They're gonna assess what exactly substance use are you taking? Is it a poly substance? How frequently used? How often have you had withdrawals? Whether review any kind of medical or mental history. Maybe they have might have schizophrenia or other mental disorder that we also have to address. We want to conduct a toxicology. We want to find out, you know, not only from their urine, but we also might want to do blood tests to kind of see if what they're telling us matches is everything. Because we have to, it had to be a truth enlightening period that everyone is on the same page. They want to conduct a thorough physical exam. We will review the prescriptions. What are they on? What medications are you on? Do you take, not only take these substances, but do you, are you on any routine medications? Do you have any comorbid conditions? Do you have diabetes? Do you have high blood pressure? What is your family history? You want to give them access to these resources. Again, we want to obtain the patient consent. This is decision point. This is, if you want buprenorphine, this is what you want. We want to really get patient-centered. Everyone's different. So we want to individualize that treatment plan. We want to review expectation. Let's make sure that we're all on the same page so we can each, everyone can go to the road of recovery. And that's key, to be transparent and to understand these are the goals that I have for you. These, what are your goals? And so we want to make sure that we're transparent. We're interviewing them in a motivated intervention way. And we want to get that prescription to them by pharmacy so they can start on that treatment. We also want to, you know, stabilize. The goal is to get them stabilized on the medication and to get them off that medicine that they're abused. So weekly visits with the patient and to target dose achieved for buprenorphine. Write prescriptions for maximum one week at a time. So it's giving them small segments of time to build stabilization. Engage and motivation approaches, you know, continue to encourage them. We want to stabilize. We want to stabilize in about two to seven days. Again, adjusting doses, you know, eliminating cravings and withdrawals from minimal side effects. And we want to continue to monitor the patient. Again, when they're coming in for office visits, we're giving them urinalysis and we're checking with them and giving them a subject of a, hey, have you abused any drugs, other polysubstance that you might be taking? Again, patients takes first dose under supervision, either at home or in the office. Subsequent doses are directed, regularly monitored over 24 hours. Patient discontinued opiates, that's the key. Understand that they must stop taking the medication. So from right to left, patient must stop taking medication. Induction day, we want to get them stabilized in two to seven days. And then once they're stabilized, they're getting weekly visits. They are, we're writing the prescription once a week until we understand that, making sure that they are stabilized on the medication. Maintenance, we want to, you know, once they've been stabilized on this medication. Again, what literature says, if one can stay on persistent for three months, there's an increased chance that they will stay stabilized and that's going to increase their, decrease their risk of overdose and maintain that they will be able to function at a high level. Adjust visits as clinic indicated. You might go from weekly to bi-weekly to monthly based on the stabilization. The prescription refills are consistent with the visits. You might want to conduct toxicologies, assess medication status, recovery, and medical psychiatry or social issues. Again, what are the resources? What can we do to help you? Refer to resources. Oftentimes, 12-step behavior groups, those peer support groups, can really continue to aid in the recovery process. But we also understand that opiate use disorder is a recurrent, it's a chronic condition. And if left untreated, it can lead to overdose, it can lead to death. So we must continue on that road to recovery by understanding that MAUD is the way that we can have access to this needed medication and go to recovery. Again, recovery from recovering from addiction, bridging the gap to recovery, it's a process. These are the references. Thank you.

opioid use disorder

medication-assisted treatment

buprenorphine

methadone

naltrexone

overdose prevention

patient-centered care