Welcome to the provider clinical support system waiver training. This is Module 5 and my name is Dr. Stephen Wyatt. I'm an addiction psychiatrist with atrium health and I welcome you. So the objectives of this particular module are to review some of the specialty areas in which you might find yourself confronted within in treating patients. I said in an earlier module that one of the objectives of office-based opiate treatment was that we would bring people into the house of medicine. We would start to get them in a place where we can start to address physical and mental health problems they may be experiencing along with some social problems. This has been shown to be highly effective. There's retention of treatment with buprenorphine and methadone and naltrexone in a way that it brings people back, allows us to continue to work with them as you would with any patient with a chronic illness. So the first section that we're going to go over, is diagnosis and appropriate management of co-occurring substitutes and mental health problems. I showed this slide once before, but I would reiterate that there's a significant overlap between mental health problems and substance use problems. So approximately 20 million people might be, slight under estimate at this point, but in that range and, a third will have mental health problems associated with that. Now, many patients will come in with depression and anxiety is secondary to the recurrent problems associated with alcohol and drug use. But much of that would resolved with abstinence. So these are really patients that with or without the substance use problem, they would be identified as having a diagnosable mental health problem, whereas in the mental health area, in the range of 44 million patients, will have mental health problems in the United States. Approximately a fifth of those patients, a little close to that will have a concurrent substance use problem. Again, I would point out that this is a diagnosable substance use problem, not that they're risky drinkers or they're using alcohol or other drugs in a less than diagnosable pattern, which is even a larger population. But again, I would just have you recognize that if you do make the diagnosis of the substance problem to be aware of this overlaps so that you have a higher index of suspicion that there could be an underlying untreated mental health problem or treated problem that needs to be addressed. So anxiety and depression are the symptoms most commonly seen at the time of treatment entry and many times these symptoms will resolve within just a few days of treatment. So if you can imagine and really think back on the DSM diagnosis of an opiate use problem and that it includes that there's been significant problems developed in a person's life. There's every reason to believe that they'd have depression with loss of job or family or financial problems in general, or legal problems that they're facing, or just the very fact that they've been living alive that they then trying to maintain their opiate use in the face of recognizing that they do things that put them at risk and create a lot of anxiety in their life. So we typically will give people some time of abstinence before we would make a diagnosis if they hadn't formally had a diagnosis of a mental health problem. I will very frequently tell people again, those that had not been diagnosed previously with a problem, sometimes even those that had done because there hadn't been attention paid to the substance use problem at the time the mental health diagnosis was made, that they typically are going to have even if they have depression or anxiety, you're going to have 10, 20, 30, 40 percent reduction in symptoms. But sometimes you'll see a 40-60 percent reduction or a 60-80 and on occasion it'll clear up entirely that after a few weeks, patients began to say, "I don't feel depressed anymore. I feel pretty good." What medications they may have been on could be discontinued. So these are referred to as both substance-induced disorder, mental health disorders, or those secondary to a substance use problem or primary mental health problems. They can really be determined as to the patient's presentation and an interview where you begin to recognize that these problems had started, that is mood instability or anxiety or even psychotic symptoms prior to the onset of their drug use. So when you do then get a person into a state of recovery and you see that the symptoms persist beyond that acute intoxication or withdrawal point of using these drugs. Then you may go ahead and consider serotonin reuptake inhibitor or other medications, mood stabilizers to help them with their symptoms. Again, we do try to avoid benzodiazepines. The patients treated with medications assisted treatment or medications to treat addiction will respond to medications like a serotonin and reuptake inhibitor very well and appropriately as well as they were not on these medications. So the ability to treat them is not impaired with also treating their opiate use problem with either buprenorphine, naltrexone or methadone. We do want to avoid benzodiazepines. So you've heard this a few times already, but there's definitely a risk at misusing and there can be potential interactions with buprenorphine. So the first-line treatments for anxiety and depression in this population would be a serotonin and reuptake inhibitor combined with psychotherapy. So there have been multiple studies identifying that medication works quite effectively. Psychotherapy works quite effectively, but the combination of the two is most effective. In terms of those patients that would come in stating that they had attention deficit disorder. This can be particularly as a psychiatrist and addiction psychiatrist, this is sometimes my notices in that so many people come in saying that they can't focus and they either at some point during their drug use, we're diagnosed with attention deficit disorder. Or certainly there it is one of the indicators, particularly untreated attention deficit disorder as a child that can lead to the development of a drug use disorder. If there is a concern that there's ADHD, then one should consider definitely trying to use a self-reported scale and we really may very well need to be referred to a psychiatrist instead of starting a psychostimulant too quickly. If they are on it and it's been prescribed by psychiatry or primary care provider, I think it's appropriate to continue them on it. It's certainly not contra indicated and using a stimulant with this medications for opiate treatment. But I will tell you my general feeling on this is there's a whole lot of reasons why people don't focus well and certainly drug use, just the cognitive impairment that can come with drug use, poor sleep and sleep habits, along with the fact that as I said before, there can be some depression and anxiety and just self-doubt that comes with recurrent drug use. All of these things can make a person feel as if they're unable to focus. So to not have either family history or early childhood evidence of an attention deficit disorder, really be very careful in making the diagnosis. Now obviously, there's a lot of young people that are not well evaluated to determine, do they have attention deficit disorder. But if the history that you get is that as a child, they were highly erratic, that they had a lot of mood instability, that they got in fights or arguments easily or they even cried easily and they were very super sensitive, this can often be identified as attention deficit because not infrequently, they're not able to stay focused. They're too worried about things. They're depressed, their moods are all over the place and they can understand what's happening to them. Consequently they're not interested in looking at the blackboard. They're not engaged and so to get some of this is what we would do in psychiatry and it's very important. This population certainly is at risk of abusing stimulants and so we're very careful in those that we might prescribe to. All right. So we just touched on adolescents a bit, but let's talk about what we do when an adolescent is determined to have a drug use disorder. So this is one of the highest populations of individuals. That is, the 18 to 35-year-olds are a big population in terms of those that have a opioid use disorder. Obviously, not obviously maybe, but not infrequently, you will see that it starts as a young person. So unfortunately, it is associated with early any drug use and it escalates in that population. So a substance use disorder sets people up for abusing their opioids or misusing them, and this consequently is a population of where we see first use. Now, an interesting point that was brought up in an earlier module is that there had been significant number of these young people, their first use was pharmaceuticals, and it still is the highest first use. But first use of heroin has been growing steadily in the last three or four years. So it's dropping down into that teenage population where there's availability of heroin, and unfortunately fentanyl that we're starting to see an uptake in that direction. So the proportion of youth actually receiving treatment, however, is quite poor. About 40 percent will have had some ability to get treatment. Actually, as you see here, less than 40 percent and it's for this reason that there's been a lot of interest in the pediatric community, pediatricians, to better understand what are the precursors to the development of an opioid use disorder, which includes quite honestly a genetic predisposition to their response to an opioid. So that's something that it's under development now. But we clearly know that there are young people that get excited when they take Robitussin codeine as a child as opposed to sedated and nauseated. That is a genetic predisposition to their response to an opioid that has the potential for setting them up for a problem when they might be prescribed an opioid for athletic injury or some other injury. For those reasons, that population we would want us watch more closely. It's certainly would include those young people that have had adverse childhood defense or had early onset of use of alcohol or marijuana. These all are just things that pediatricians are getting greater awareness of in terms of their own use of opioids and exposure to opioids. But then if that happens, that they're better prepared for, and this includes primary care that takes care of a huge portion of our population, the adolescent population, that they're better prepared to actually treat opioid use disorders. So the DATA 2000 does authorize that we can treat individuals 16 years or older with buprenorphine. Methadone, you can treat at 18 years old. However, there are waivers to that. It's clearly identified that there's an unsuccessful attempt to treat with withdrawal management, and this is variable within the states. But for the most part, if a young person were going to be treated with methadone and there's clear indication, we can typically do that. These days, it would be more common that they would be treated with buprenorphine and then in some form of adolescent program. If they're pregnant as an adolescent, they have priority to actually starting buprenorphine and other treatment modalities, and we will be reviewing pregnancy in a moment. So the American Academy of Pediatrics recommends that pediatricians consider offering medication-assisted treatment to adolescents and young adults with severe opioid use problems and/or discuss the referral to other providers. As much as anything these days for all providers to know that these treatments are available and make sure that that option is made available to the patients. So when there are multiple evidence-based treatments for a disease, we want to review what are the options the patient would have, and to not include that medication could be helpful and actually statistically shows greater improvement would be a poor practice of medicine. The FDA approved medications options are buprenorphine as already stated, 16 years or above, and is typically considered the first line choice. A significantly decreased use of opioids and cocaine have been noted with the use of buprenorphine. The cocaine part is primarily that we get people back in treatment. This has been reiterated numerous times throughout these modules that if we can see people again, we can continue to address where they're at. In some ways, it's a harm reduction model that we may accept certain things, maybe some limited or some use of marijuana, but you continue to monitor that and continue to talk to them about coming down the dose and the risks that it puts them in or other problems. Not infrequently. People, if they're engaged in treatment, they will make these changes in their lives over a long period of time, which hopefully these adolescents have an opportunity to travel, they will have significant changes in their lives. Methadone is available as described at 18 years old as is extended release naltrexone. Psychosocial treatment options would include family interventions, vocational support, and other behavioral interventions, highly effective in this population, but you got to get them stabilized. Sometimes that would include the use of a medication. All right. So pregnancy. About 21,000 pregnant women between the ages of 15 and 44 have misused opioids in the last month. The prevalence of opioid use among women who gave birth in the United States between 2000 and 2009 was in the range of 1 to 5.5 Per 1,000 births. This is only grown since then. We're hearing this frequently, and it's become very clear that we need to be paying closer attention. We need to be screening for these problems during pregnancy. Try to pick it up in a way that then would result in both a healthier pregnancy, but a healthier woman and child going into motherhood. So it is a real opportunity, and I say that in part it's an opportunity because no matter what, typically there's strong evidence that women are going to reduce their drug and tobacco use during pregnancy across the board without treatment. There's going to be some wild reduction. This has been identified many times. Now obviously, there are exceptions to that. But for the most part, they want to have a healthy birth. So if you can actually get them engaged in treatment and decrease their cravings significantly, then they are going to have a greater potential to look at these other factors that could impair a healthy birth. So that's one of the real strong points of this work and of trying to get women stabilized. The American College of Obstetrics and Gynecology and American Society of Addiction Medicine recommend that screening that I talk about, a comprehensive screening at the first prenatal visit, and then using Screening Brief Intervention, that's this acronym SBIRT, and other screening tools. So the 4P's are what's the family history and what history can you get from the family. So history of drug use disorders and what can they tell you about the past. Does the partner use? What's the woman's continued exposure to alcohol and other drugs? What's the patient's past use of nicotine products or tobacco products and other drug use? What's the present use? It's typically stated in the month prior to you learning that you were pregnant what was your use. That's a strong indicator of would they be struggling during their pregnancy, but not damning them in some way where they feel very uncomfortable saying, "I used yesterday and/or I have continued use." But these things, these are screening tools. So these are ways in which you can pick up there may be a problem and I may want to dig a little deeper. The CRAFFT has to do, it's an adolescent screening tool, and the C is for: Have you driven in a car with someone that's been using drugs? Have you used drugs to potentially relax or allow yourself to fit in? Have you ever used alcohol or other drugs alone? Do you ever forget things that you did while using alcohol or other drugs? Have family or friends ever told you that you should cut back or stop your drinking? Have you been in trouble associated with alcohol or other drugs? Again, it's a screening tool, but it's a very effective screening tool and picking up things that could be more of an indicator of a true drug use disorder. In the adolescent population, that's where it's used. So buprenorphine and methadone in pregnant patients with an opioid use disorder has been used very extensively in the method on population in the past. It has been thought of as the treatment of choice because we had so much more information, and not infrequently OTPs will have a pregnancy programs, a mother's program that will allow them to get some prenatal education and that sort of thing, and it is more structured and there's consequently less risk of diversion of the drug and more long-term data on outcomes just because we've been doing it a lot longer. At the same time, buprenorphine has been shown to be equally effective as methadone in maintaining women and recovery during their pregnancy. The rates of adverse events during pregnancy, not delivery, but during pregnancy are about the same. There's a lower risk of overdose. As we reviewed in previous modules, buprenorphine as a partial agonist used alone has little in the way of potential for overdose in the pregnant mother. There are fewer drug-drug interactions, there's less frequent neonatal abstinence and milder symptoms. Now that is reportable. At the same time, when we look very closely at these populations, like what I'll show you in a moment, the MOTHER Study results. There's similar evidence of mild symptoms so that we would say there's a similar identification of neonatal abstinence in these two populations, but the severity of the symptoms is less in the buprenorphine population and less a shorter period of time. So there's a decreased need from working with the infant and often shorter hospital stay and duration of treatment. So methadone again has been the first-line drug, it's still commonly used in pregnant women, it's not wrong by any means to be using. It is used high enough doses, sometimes because of the increased metabolism, the dose will increase some during pregnancy. The changes that take place typically are going to take place both buprenorphine and methadone in the second trimester. But at the same time, because of increased metabolism and increased circulating blood volume, there may be a need to increase the dose. So if you're going to make changes, we typically do it during the second and third trimester, either increasing or decreasing, and methadone not infrequently would we be increasing the dose. They also may need a split dose and that turnover is greater in a 24-hour period. With advancing gestational age: Plasma levels of buprenorphine progressively decrease and clearance increases, so the half-life methadone falls on average and compared to the non-pregnant women, about eight hours. Along with increasing doses, splitting the dose can be helpful. Something to keep in mind is that it is the on-again, off-again effect, the erraticness of drug use during pregnancy that is highly associated with some of the problems that we see during pregnancy with opioid use. Now opioids, interestingly all these modules, I mean we're talking about a medication, a drug that our bodies are able to tolerate quite well. It's not like alcohol, where excessive use results in really toxic effects to multiple organs. Opioids, we have natural opioids. It is the behaviors associated with it, it's the profound addiction that can take place with the opioids that results in high-risk behaviors that put the infinite risk, and they put it at infinite risk because of these potential, obviously for infection and other problems that would take place with the mother, but also her behavior during pregnancy or eating habits, or sleeping habits, or just the erraticness of her life. The more that we can have a very stable dose of an opioid in the system, the more the system will adapt really very nicely, and as the system adapts nicely, so with the infant, and that erraticness increases the potential for neonatal abstinence. So the erraticness of an uncontrolled opioid use problem during pregnancy or the up and down, even with methadone can result in increased neonatal abstinence. So there has been some indication that using a split dose would be better. We don't typically need to do that with buprenorphine, and I'll go over that now. So this was the MOTHER Study, Hendrée Jones was a lead author and it was the New England Journal in 2010. Here, what you're seeing in the first graph is that the mean total dose of morphine was significantly less. So one-tenth the amount needed to treat neonatal abstinence in buprenorphine exposed infants compared to methadone. The mean hospital stay was cut in half. We typically still are adjusting, these children should be observed 4-5 days, the shortest would be three days, because it takes more time for people to start to have withdrawal symptoms from buprenorphine. So we couldn't necessarily say that if they don't have any problem within the first 24 hours, they're not going to have a problem, and so they do need to be observed. But there is less time typically needed to treat their problems in the hospital if they've been on buprenorphine compared to methadone, and that's shown in the last graph here. The use of buprenorphine with or without naloxone has been something that has recently been discussed, and there's literature identifying that there is little in the way of problems associated with using the combination product in pregnant women. So initially, the idea was two-fold, one that we don't want to give a woman any medication that they don't need during pregnancy. But at the same time, as I've already described, if the product is used appropriately, they get very little in the way of naloxone anyway and so in the sublingual use of naloxone, there's no more indication that it's a problem with the pregnancy compared to buprenorphine. So very comparable if used together. At the same time, one other reason that we didn't give it is that a huge problem with the opioid use patient as I've described, is that erratic use and the potential that they would go into withdraw. So if they were going to divert the problem, just divert the medication to injection drug use and they inject the combination product, they're going to potentially put themselves into moderate withdrawal, which is contraindicated during pregnancy in an acute precipitated withdrawal. So that had been the ruling, and as I also stated in an earlier module, if there are eight milligrams of the combination product at the time of pregnancy, then we switch the [inaudible] take eight milligrams of the monoproduct, when pregnancy is over, we switch them back. I've done this numerous times and other than potential side effects, there's no feeling of withdrawal. They do not get enough of the naloxone to really change the treatment at all. So this is a one-to-one conversion. So what's been found more recently, and some of this work has been done also by Hendree E. Jones, is that there's no significant dose increase needed. So during that third trimester, we don't typically increase the dose. In postpartum, there's gradual transition to the original buprenorphine, as I've already described. So if you're taking the monoproduct and switching them back. We've identified that the combination is a category C, that there's no clear teratogenic effects in animals and also in humans. We do have some evidence that there's no significant difference, but that's been the problem. So now it's very difficult to do studies on pregnant women. But there's been various significant increased evidence that the combination product is safe in pregnancy. I do think that you are going to be seeing this more and more, and I think that the control places, people that do a lot of this including myself, you're going to see more and more use of the combination product and less and less use of the monoproduct. I do believe that over time it will be the recommendation. I'm not saying at this point in time that switching into monoproducts is inappropriate, but you would have good evidence backing you up if you decided to use the combination product. There has been some evidence of women coming in to a provider saying they're pregnant, getting the monoproduct and they're not pregnant, but they just wanted the monoproduct because there's higher street value or they could use it by injection more easily. These are the things that we know and really increase our awareness of the problems with the monoproduct. I wanted to be clear about that. So either way, you would keep them on the same dose at the time of pregnancy of buprenorphine. Right now to use the combination product, there is good literature. The monoproduct is certainly the way in which it's been written and used for many years and so to use the monoproduct would also be certainly appropriate. Because of more deep dive into neonatal abstinence, there is evidence of growing neonatal abstinence in infants being born around the country. Many of them, if they're looked at very closely, they're going to have some mild symptoms, but there is a threshold. We use a Finnegan scale. The threshold in which the identification of symptoms is severe enough that we would start treatment is in the range of 50 percent. Those symptoms include increased irritability, fever, diarrhea, hyperreflexia, seizure, and this can be associated with poor feeding. So these are the reasons. So we want to be very careful and treat it appropriately. We'll typically see it within those first 72 hours. It peaks within three or four days and can continue for up to a week. If they get started on medication, that taper then can extend their treatment beyond a week. So complications include the untreated opioid use disorder patient, it's clearly worse, and increased risk of placental abruption, preterm labor, maternal obstetric complications, and fetal death. This is untreated opioid use disorder. So these are the potential problems to the pregnancy and a poor outcome. So medications, the opioid therapy is the preferred first-line intervention for the treatment of neonatal abstinence, typically with either morphine or methadone. There are some groups around the country that are using buprenorphine to treat that also, which, again, has a very soft landing. Because it's tapered off, feathered off, there's reason to believe that it could be a very effective, and it's been shown to be effective in treating neonatal abstinence. Or clonidine, it helps to agonist to reduce the effects of the excessive norepinephrine that the infant's experiencing withdrawing from opioids. There are also some great, great programs around the country that are using non-pharmacologic approaches, which include rooming in and getting the baby with mom early, during the Finnegan evaluation with the baby with mom and reducing significantly neonatal intensive care unit stays. Because if we start morphine or methadone, then they're locked into a taper of those medicines. So if we can help the infant stay more calm and use non-pharmacologic techniques, then typically infant gets to go home with mom hopefully more quickly, and potentially like rooming in, the infant's with mom and there's more bonding early on, right from the beginning. Buprenorphine is not contraindicated nor is methadone, but buprenorphine in particular is not contraindicated with medications as treatment. There is a small amount of methadone transferred to the infant. Just to be clear, there have some evidence that it actually can reduce neonatal symptoms. So we know that they're getting some, but we don't see that with buprenorphine and I think it's interesting in part because the level in human milk is low and so the calculating infant exposure and maternal weight adjusted dose is very low. The other piece about buprenorphine is that the gastric absorption is also extremely low. So not only is there a low dose being transferred, but the absorption in the gut is low. I often pointing out these infants are not holding the breast milk in their mouth trying to get absorption of buprenorphine. So women can remain on the medicine, stay very stable, and have healthy babies that are not getting significant exposure any longer to the opioid. All right. So let's talk about pain. We're going to review the management of acute postoperative and chronic pain while the patients are taking buprenorphine. So acute pain management of buprenorphine maintained patients, it can be approached in a variety of ways or can be approached in a variety of ways. First of all, all the non-opioid analgesics are very effective. So for many problems, we can add a non-opioid analgesics to their current dose of buprenorphine and they can do very well. They typically are maintained on the same dose of buprenorphine. You don't have to bump the dose up but if the pain is not managed well with a non-opioid medication buprenorphine has for acute pain, a 30-to-1 morphine equivalent. It is a very effective pain medicine. So you can increase the dose somewhat and/or split the dose. Now, I say, and/or really you need to split the dose. I can tell you that many times if they just split the dose. So if they're on eight milligrams, they may take 2,2 and 4 or they're on 12, they may take 4,4 and 4 throughout the day. That's four milligrams three times a day. The splitting of the dose increases the analgesic aspects of buprenorphine significantly. So it maintains them out of a problem in terms of their cravings for good 24-36 hours. But the analgesia properties of it do not last that long and that's why we split the dose. Again, it can be very effective. Rarely, quite honestly do people need to go up on the dose and I'll talk a little bit about what other things you can do in terms of other medicines. We have been in this situation certainly where the problem is acute enough that you would stop the buprenorphine and start full opioid agonist. During that period there is severe pain, like a major motor vehicle accidents or compound fracture, stabilize them and then transfer them back on to buprenorphine at the time that the severity of the pain has been reduced. I will tell you, and it's important to recognize that many of these patients are very fearful that they will be mistreated, that they're not going to get a proper pain medication. So it is important to just first of all, listen, help them understand that your goal is to help them with the pain. But at the same time, you don't want to get back into that problem. I want to see you stay healthy. Let's work closely together so that we can control this pain but not reblossom your old opiate use problem. This often includes working closely with whoever the surgeon or the other provider is, that's going to be involved in the management of their pain. So frequently, really the good standard of care would be to talk to the surgeon and talk to anyone else that's involved in the management of their pain, in the opposite way. We will go ahead, let me finish this. The Post Op options for patients then includes continued full opioid agonist and then eventual transition back to an antagonist. So you consider certainly using initially a short acting and then moving into an intermediate or longer acting medication if need be as per the degree of pain that they're experiencing. Be very clear about the potential risks of relapse if they startup full opioid agonist and the need to keep security around the medications and sometimes that security that others in the household may have exposure to the medicine or that, you want to call in a partner to help monitor that the patient is not overusing or misusing their opioid. People that are strong in their recovery will be often very receptive to these ideas. I'm telling you that if you stabilize someone and you really get them engaged in treatment, they do not want to fall back into it. If you talk to them in that way, it can be very helpful to building a partnership of what are the things that we could do to help you stay more safe. You can continue the partial agonist at the same time, but you need increased dosing. You may consider increasing the dose but you still need to have it as split dose. Then, you have clear detailed discussion with the patient about returning to baseline dosing and what your anticipation is of the timeline of that taking place. So if a person's on naltrexone for mild pain, again, we would use a non-opioid. So they are going to respond to all the non-steroidals or regional blocks or other ways in which we might treat mild-to-moderate pain but if they're having an elective surgery, then you'd want to time it for when you're going to stop the antagonist and the patient be in a state where the opioid receptors are now receptive to a full opioid agonist. This may be 72 hours for oral dosing or four weeks after their last injection. For major pain or emergent pain, certainly regional anesthetics, conscious sedation can be very helpful. But if they go on a general anesthetic, the anesthesiologists can override it with these high potency fentanyl analogs that can be very effective in the treatment of the patients pain. So they're not without potential for getting good care and pain relief. This brings me to a point and that is, on the PCSS website, there are multiple modules and webinars about all the subjects that I'm describing and in further detail than what I'm describing in this waiver training and I would encourage you to go there if you have interest in pregnancy or in pain or adolescents or whatever it might be. There are a number of detailed modules and I bring that up and that there is a specific module to the control of pain with patients taking naltrexone or one form or another naltrexone. So acute pain management where the person currently on methadone, you may want to consult a pain specialist, it may require higher doses of methadone or higher doses of an additional full agonists. So it's a little easier with methadone because we can just use a full agonist on top of it, whereas there may be some greater difficulty moving back and forth with buprenorphine because of the pharmacology of buprenorphine. But you would want to potentially consult a pain medicine specialist and you're then able to think about, or understand, or consult around other modalities, multi-disciplinary approach to the treatment of pain, and either non-pharmacologic or non-opioid therapies that could be very helpful. Let me say one last thing about chronic pain patients. So I've, in the last couple of years, been working with patients with sickle cell disease. We've been able to stabilize their opiate use significantly, but I will tell you that there's then much more clear evidence that you can use a full opiate agonist on top of buprenorphine. I know that that seems contrary to what we talked about in earlier modules about the pharmacology of buprenorphine. But if you think about if they're on eight milligrams of buprenorphine a day, maybe in a split dose, they're not occupying all the opioid receptors. So there's still room for using a full opiate agonist on top of their buprenorphine to reduce an acute pain episode. So these sickle cell patients maybe taking two milligrams three or four times a day, chronic control of their pain, and then if they have crisis, they're typically hydrated in the emergency department and potentially given an injection of hydromorphone or something like that, higher potency opioid to help them with that crisis, and then they typically have been able to go home, and we've been able to reduce not only those emergent visits, but also we've been able to reduce significantly the repeat visits or stay hospital admissions. This is also coupled with red cell exchanges and some of the great things that are available now for patients with sickle cell disease. Older patients being treated with medication-assisted treatment. So the general population is older individuals is rising, it's significant, and the number of people with substance use problems is also going up in this segment of the population. So this is the baby boomers aging and it's a group that had had a low tolerance for drug use back in their teens and 20s, and then maybe some reduction. But now they're retiring and they're starting to use alcohol and other drugs. So it is one of the fastest growing populations. So they're not one of the highest, but fastest growing populations of people that are at risk for this. For a variety of reasons, using opioids, and particularly using opioids and benzodiazepines in this population, puts them at particular risk. That's because there is some decreased metabolism of these medications, increased elimination times that they hang around longer, not infrequently these folks are on a variety of medications at the same times. There can be polypharmacy going on which is altering the metabolism even further, multiple comorbidities including cognitive decline so that they're not, in some incidence, even remembering when they took their last medication. So it just becomes more and more of a problem, and pain is highly prevalent in this population. So a person would have 24 hours of pain within the last month increases dramatically in this population. But certainly, the population of chronic, those with chronic pain, artery disease, and various other pain problems increases dramatically with age. So the potential for them having unintentional overdose increases significantly. But the other thing to keep in mind is that this also, particularly elderly males, there's a higher incidence of potential suicide. So thinking about these things, thinking about depression, how they're dealing with pain, what other social supports could be put in place, those sorts of things is extremely important to consider. So you want to do a good evaluation as you would with anyone, but at the time, really do a good screening. I've had a number of times where I've done an evaluation, and I come out, and I talk to family, and they will say, "Did you ask them about their cocaine use?" Well, in the old days, I had been a former emergency physician in the '80s and I may not have because I didn't consider that this 70-year-old male is using cocaine. But this drug use is ubiquitous and it can happen at any age group, at any social economic position or status. So it is important to do a full screening, and that same assessment that we described in the previous module is important. So assist patients with the cognitive impairments and assess for suicidality as I've described. Medication recommendations, which include buprenorphine, that's really first line, it can be a very good choice because there's increased susceptibility in the elderly to respiratory compromise. So we've talked about this before. Buprenorphine slows respirations, but it doesn't bring it down to zero and then no response to CO2 rising. You do want to start at a low dose and titrate up. We do that with pretty much everyone. But you want to be particularly careful in the elderly because of the slower metabolism, and hepatic metabolism can affect this. So you just need to be careful. Methadone, there's certainly more drug-drug interactions and we need to be more careful about QT prolongation because the elderly are more susceptible to that or taking polypharmacy in a way that there could be other drugs that they're using that would also complicates QT interval conduction, and methadone has a potential for higher risk for overdose. All right. So we've talked a little bit about the other core morbid physical problems. But in looking at HIV in particular, again methadone and buprenorphine are metabolized by the cytochrome P450 3A4 enzyme. Many of the antivirals will affect these buprenorphine and methadone levels, and in some cases, buprenorphine methadone levels will affect the antivirals. This was more of a problem with some of the earlier antivirals and methadone. Consequently, there were some significant problems, and one of the reasons that we often would try to get people onto to buprenorphine, so that's something that we watched very closely. Providers should consider referral to a specialized HIV treatment clinic when it's available, so both methadone and buprenorphine. Methadone treatment centers can have specialized clinics treating people with HIV, have HIV clinics that are now using buprenorphine. So I was involved in the first use of buprenorphine in the Nathan Smith Clinic in New Haven back in the late '90s, and did show some increased compliance with their medication, their antivirals. What we've also seen, and I've said this numerous times, is that they're retained and treatment in a way that you get to talk to them about any other drug use. So we also saw a reduction in poly drug use, other drugs that they may be using, cocaine, stimulants, marijuana, alcohol while getting treated for their HIV. Liver and kidney impairments, and is there change in the dosing? Buprenorphine is certainly suitable for treatment with patients with renal difficulties. There's no significant difference in the kinetics of buprenorphine in patients with renal failure versus relative controls, and there's no significant side effects in patients with renal failure. Buprenorphine and methadone can be prescribed to patients undergoing hemodialysis. They are metabolized in the liver, and there's a limited amount that's excreted in the kidney, so it's not changing things dramatically. On the other hand, buprenorphine does have undergo hepatic metabolism. Again, the 3A system. So patients with significantly compromised hepatic function could have slower metabolism of buprenorphine resulting to higher blood levels. At the same time, there's no specific hepatotoxicity that's been demonstrated for either methadone or buprenorphine. So even though we watch these levels, there's very limited evidence that it actually can cause problems. People that have hepatic dysfunction already all should be monitored more closely at blood levels and just see that because they could be on multiple medications that are metabolized in the liver along with either methadone and buprenorphine. We want to be careful about that, and we would potentially then follow their transaminases more closely. If they have current hepatitis with impairment and hepatic function, then it would be contraindicated, and we need to get those problems under control. If there's just mild elevation of their enzymes and they are hep C positive or hep B positive, they can still be treated. I say that in that I've had a number of patients we determined that they are hepatitis C positive, I sent them to hepatologist, they always want them to be continued on their medication because, obviously, we're controlling the problem that most likely, most frequently results in them being hep C positive in first place. So typically, injection drug use, and this is highly prevalent, it's really endemic in this population. It's not a contraindication to starting people on medication [inaudible] treatment. So in summary, approximately 40 percent of adults with substance-use disorders have co-current psychiatric problem, although buprenorphine is approved in individuals for 16 years of age and methadone and proved for individuals 18 years of age along with Naltrexone. We don't see a big uptake in using medications. Again, it is highly effective if the patient has tried to come off the medication, they're off these drugs not off [inaudible] and continued to use. So we typically, particularly if it's a short period of time that they've been using opioids illicitly, then we will try to taper them off. The idea that we do in acute withdrawal, that can be three to five days or it can be three to five weeks. So some programs we will start them on buprenorphine, get them stabilized, taper them off over just a few weeks with strong cognitive behavioral treatments and see if they can remain abstinent and do well. If there's recurrent relapses then to have them on maintenance dose for a longer period of time can be very effective. Again, I've had many patients where a couple in particular where I started down at 18-19 years old, the family is like, "We don't want them on it forever." But then the patient gets on them, gets back to work, finishes school, high school in this regard, in this case. At the time that they're going to start college, the family comes back and says, "Well, do you think you could keep them on it for the next year, at least six months until they get stable in college." So people around these folks that see significance changes, significance improvements in our lives, where they may have been resistant, why do they need the medicine? Once they get on the medicine, they see that stabilization, and that their old family member, a friend comes back, a partner and they want them to stay on it. Methadone has historically been considered a first-line drug for opioid use by pregnant women. However, increasing evidence demonstrates that buprenorphine and noloxone is well-tolerated, efficacious, and potential benefits for the newborn. That is, reduce symptoms associated with opioid withdrawal. Peri-operative pain practices for patients with opioid use disorder are variable and require close coordination with the surgical team, so you should be in touch with them. Typically, they come off 24 hours before an elective surgery and they'll do fine, but they need to talk to the surgeon. Buprenorphine is a front line treatment for older adults with opioid use disorder, particularly those where there's high potential for interactions. There are markedly fewer drug-drug interactions with buprenorphine and antivirals compared to methadone. Buprenorphine is suitable to use in patients with renal failure, so no problem really unless the patient has an acute stage of their hepatitis, then pharmacotherapy with methadone and buprenorphine is not contraindicated. We may still watch their transaminases over time, but typically, they're going to stabilize. They're not going to get worse, they're going to get better. That completes Module 5. So here are the references for this module. There's a few here, and you can review those as you'd like. We also have an appendix that gives you more indication about some of the interactions of antiviral agents with methadone and buprenorphine. So those are also made available to you in terms of information if you are treating patients with HIV. With that, I thank you for completing this module, and I, again, encourage you to take a look at the PCSS website for more information, particularly on these areas of really specialty care, special populations that we are often confronted with or that we see in this population. Thank you very much.
