Hello again. This is Dr. Steve Wyatt and we're now going to review Module Six of the PCSS Waiver training. This module is to review the Medication Assisted Treatment, like actually how do you do this, and then we'll spend a little time talking about urine drug testing, drug testing in general. So we're going to start with the induction. We talk about it as induction, but it's initiation of buprenorphine, and then we'll be reviewing the indications, the steps for how do you adjust dosing after you've started it. We will spend a little time talking about naltrexone, another form of medication for addiction treatment, and then end with some information around drug testing. So to review, the overall goal of buprenorphine induction is to assist the patients in switching from an illicit opioid or non-prescribed opioids to prescribed buprenorphine. In many ways, the goal really is to stabilize these in a way that then they can start to move forward in other areas of their life, and at the same time as health care providers, we will be helping them with either of their mental health or physical problems that they may be troubled by or affecting their health. So specific goals are really to identify the dose at which the patient can reduce, hopefully stop entirely, their use of opioids. Decrease any kind of withdrawal symptoms that they might have, and we'll talk a little bit about using buprenorphine as a withdrawal management medication. But again, we want to be able to make this transition most smooth for the patients so that they stay engaged. They shouldn't have much in the way of side effects, typically. We've talked a little bit about that in previous modules, and certainly, a major goal is that their cravings go down significantly, and so that they, again, can get on with their lives in a more healthy way. So there's a variety of things that you do need to establish with the patient before initiating the medication. Certainly, to know how they're going to pay for this. You want to confirm what pharmacy they're using, and typically we like to establish one pharmacy that they're going to be going to, and so that there can be that sort of relationship maintained between the pharmacy, yourself, and the patient, and then where and how will they be getting typically urine drug testing. But some form of drug testing will be important. Now, the induction can be done in a couple of different ways. Typically, and what I would highly encourage is that you would start off doing some in-office inductions, and we'll talk about the reasons for that in a moment. But in that scenario, you would be providing them with a prescription. They would go to the pharmacy. They would have instructions on how to, that we're going to go through, on how to be prepared to start the medicine, and they would come in the office and take their first dose. Alternatively, it can be done at home, and it is being done very frequently around the country at home, and this has potential other complications but at the same time it's very straightforward, and can be done very effectively. So one of the things that you need to think about is how is this going to fit into your office, and many providers will only do inductions early in the week so that if the patient has a problem, that they would be able to then be available for questions or problems the patient might have. So very frequently this inductions are done Monday, Tuesday, potentially Wednesday, and so that the patient's not going through their first day of being on the medication on a Saturday. I will tell you that I typically will do inductions first thing in the morning. That allows for them to have a period of time since they took their last opioid, and typically overnight. So a fair amount of the time they're asleep anyway, and then I would typically see them early in the morning, typically around eight o'clock, and so that then, again, you'll be able to have time to follow them a little bit in the office, and be able to be available if there's problems later in the day. You want to clearly establish, and this is a real key to this module and to effective induction, is that patients need to be in moderate withdrawal. If they're in moderate withdrawal, and you're not asking them to get real sick, you're saying six or so hours beyond the time in which they would normally take another dose of medication or any opioid. If you get to that moderate withdrawal, and then you start with a low dose of buprenorphine, two to four milligrams, patients will very typically, do well. I know that a lot of interest and some concern at around the idea that patients are going get sick but I can tell you having done this probably well over a thousand times, I've only seen one patient that really had any kind of problem, and it was a little uncertain after actually what happened in that particular case. If you've started at a low enough dose, if you think about that graph that we showed you where buprenorphine has about 40 percent intrinsic activity, and you want to have patients down below that 40 percent or around that 40 percent place, you give buprenorphine and they feel fine. If they're a little above that and you give a low enough dose, it's not going to drop them down significantly down below that 40 percent, because there will still be some opioid interaction with the receptor, and if you give a low enough dose. So again, really important that you establish this mild to moderate state of withdrawal before initiating the medication. These are the things that you would be looking for, and they're part of this Clinical Opiate Withdrawal Scale. So they have been increasing their pulse. I typically will just touch their hand. The idea that there's sweaty palms. They can talk about restlessness, but sometimes you can observe it. They can talk about nausea, but on occasion, they're so far into withdrawal, they may actually be sick to their stomach, but I've never had anyone vomit in the office. Tremor is easily identified early on. It can be they feel tremulous, but certainly as time goes on you can see mild tremor. Pupillary size is one that I also always look for. It's pretty easily identified and these would be more objective signs; so increased pulse, maybe some sweaty palm, dilated pupils. Hard to say that they are actually having joint aches. These are more subjective. You may see yawning, they may appear to be anxious, but they could be anxious for other reasons. So this is, again, somewhat subjective. Gooseflesh is something that you can pick up frequently, and runny nose or watery eyes. It's a little later in withdrawal and so not typically seen at the state that they need to be in. If they're having those sorts of symptoms, clearly they're ready to initiate the medication. When we give instructions, and it's real important that you give instructions on how to properly administer the medicine, it is typically sublingual. There is one product that actually sticks to the side of their cheek, that's a product called Bunavail. But the common products, generic and some tablets are held under the tongue. We typically then advise people that you need to allow it to completely dissolve. So if you don't feel any further film or tablet particles under the tongue and then leave it typically three or 4-5 minutes after it's dissolved before they would either swallow it or spit it out, because they're really not going to get any more medication if they swallow it. Once it leaves the mouth, the bioavailability is reduced significantly. So again, people will sometimes spit it out. There is some evidence that if you spit it out, there may be less nausea and I've had some patients say that it helps with any side effect like a headache that they might experience. So again, it can be either way. I would say the majority of patients will go ahead and swallow it. They can take a drink of water, moisten their mouth. They don't want a pool of water under their tongue or anything like that and you want to have them avoid acidic juices, anything that's going to cause vasoconstriction within the mouth and the buccal mucosa, you would want to have patients avoid, so coffee and juices. I typically tell people not to smoke a cigarette or use any kind of nicotine product for at least 15 minutes before administration of the medication. I know some will say a half hour to an hour, you can say a lifetime, but it is important to let them know that nicotine will also cause that vasoconstriction and reduce absorption of the medication. Once the medicine is in there, take a few minutes to just allow it to dissolve. Don't talk, don't drink anything else. In some ways, tell people to just put their head down and allow that saliva buildup to just pool in the front of their mouths, under the tongue can be helpful for some patients so I at least suggest that to them. I think another very interesting suggestion that I've heard from a few different providers is this could be a time where you do or read a daily affirmation or just consider one's recovery and what am I working on today? How will today be different and that sort of thing? I say today and most of the time, the medication is delivered or people want to administer it in the morning, though it's not a problem if they feel more comfortable taking it at night. Most of the time, people get a little bit of activation from it and like taking it in the morning. But at the same time, some patients, like I say, will elect to take it at night and it doesn't matter. Typically, they do take it once a day, not in a split dose but there's not a problem taking in a split dose. It's just that if they take one today, then they just get on with their life and not thinking about, gee, its four o'clock, I get to take another half of my dose. All right. So all the products are roughly a four to one formulation. So these are the generic tablets, it's the same for the Suboxone product, the Zubsolv, Bunavail. These products have different bioavailability so they're different amounts of the medicine, but they're still pretty much in the four to one formulation. That is four times the amount of buprenorphine to the amount of naloxone. This is the formulation that we know. There's not much of any interference with the naloxone and the primary product obviously is buprenorphine. So if the patient arrives on day one and they are not in the degree of withdrawal that you feel that you're ready to start the medicine, like they're not in the mild to moderate state of withdrawal, then you would want to confirm when did they last take an opioid, whether the instructions are complete. I read about people saying, well, you told me not to use heroin after midnight or not midnight, typically around six to eight o'clock at night. So there's a good 12-14 hours before they would start the medicine. But you didn't tell me not to take an oxycodone or something like that. So you want to talk to them about when did they take it. If they are very clear that they took it 12 hours ago, then you may then have them either wait in the office or if you have availability that you can see them in an hour or two, let them go for a walk or do something to sit in the waiting room until the withdrawal symptoms increase and you can start the medication. The other would be if they didn't follow the instructions at all then they may need to be assigned to starting on a different day. I will say that the or here is if you give a low enough dose, there's very little risk in terms of precipitating withdrawal. So I say that, and I mentioned that earlier, that if they're just above the 40 percent intrinsic activity that buprenorphine is going to be providing and you give a low dose, it's not going to drop them down precipitously. That's the importance of not starting with an eight milligram tablet or film or other product and instead start at a low dose, give them some relief and then titrate it during that first day to their point of comfort. If you give too much to almost anyone, it's going to drop no matter what state of withdrawal they're in, it's going to drop them and they're going to feel uncomfortable. So again, you want to start low and go slow. It's not always and in fact I've done probably hundreds of inductions utilizing an eight milligram tablet, break it in half, then put four milligrams in their mouth. So certainly four milligrams is very easily tolerated. But if there is any question at all about their state of withdrawal, I would start at two milligrams. More frequently now, I actually do start at two milligrams just to avoid any problems that they might experience. So again, your instructions when they're going home with the prescription, they go to the pharmacy, they get their prescription, that night they don't take any buprenorphine. I tell them, "Come in with a bag stapled closed," and then they take the last of whatever, their opioid as at the six o'clock. That is what I tell them, at night, and then they return to the office the following morning. If it's a short acting, 12 to 16 hours after that short acting. If it's a long acting opioid that they've been on, then you obviously want a longer period of time, and typically for sustained release opioid it's about 24 hours. Methadone is variable and it's a little more difficult. So we typically will say at least 36 hours after their last dose. I will often say 48 hours that is on if they're getting methadone treatment program, they would get it typically dosed in the morning and then wait two days before then starting the induction, and they are not in severe withdrawal by then. They typically tolerate that very nicely. It should be noted that because of the availability now and how often we're seeing fentanyl, you may want to have them in a little further withdrawal, so that you can see that the very powerful opioid is more out of their system before you start buprenorphine so that they don't have an adverse response, and again, I'm not talking severe response. If you start at a low dose then go slow. That's important in a variety of areas of medicine, but certainly in this case. They're going to get comfortable even with two milligrams starting it if they're in a mild-to-moderate state of withdrawal, and then we will obviously be titrating up from there according to their needs. So patient on short acting that's heroin or oxycodone, hydrocodone, stop the medicine 12 to 24 hours prior to induction. They arrive in mild-to-moderate withdrawal, and then you want to see the COWS, clinical opioid withdrawal scale greater than an eight. I will tell you that because you can reach an age just by a patient subjectively telling you that got signs of withdrawal, I typically will even try to see that they're around in 11, allowing you to see some objective signs, before you actually start the medication, and then you want to document what level of withdrawal they're in by the COWS and then track their response that first day. Just giving you some sense of the severity of their opioid use problem and the response to their medication. If they have been on methadone, we want them to be down to at least 30 milligrams a day. There has been some consideration that for a day or two prior to stopping that they actually be on 15 milligrams, but I've done a lot of inductions going from 30 milligrams, and it's hard sometimes to coordinate this with an opiate treatment program. Again, I would encourage that you go about 36 hours to 48 hours. So here they're saying no method on the day after dosing and then the following day. Typically they're going to be on a candidate to start low and go slow and inducing them to buprenorphine, and literally everyone that you're doing is you're looking for mild-to-moderate withdrawal. So in review, the first dose is two to four milligrams, and again, many people are going to do just fine starting at four milligrams. I sometimes find it easier just to write for two milligram tabs, so that there's some ability for titration and they're not breaking tablets in half. There is a four milligram film that you could write for. Sometimes it's a little harder to get because it's not as commonly used. So many pharmacies don't stock it. But again, I certainly write for it, and once you establish as certain pharmacies, it can be used very effectively. After you started in the office, you would watch them for an hour or two. Usually within an hour and a half, you'd have a good sense of, you're moving in the right direction, you could then redo the COWS, see what level of withdraw they're in, and typically redose at that point with another two milligrams sometimes four, however, often if I start with four, I will see how they're doing. They're typically really doing quite well. They feel much more comfortable, and I'll tell them, why don't you wait awhile then you can redose again in a few hours at home. So they would take the last half of that eight milligrams at home. Then you're going to want to titrate as per typically craving. I will tell you that the majority of the time now I'm typically starting at either eight or 12 milligrams, and I would like to tell you, if they're using, a bundle which is 10 bags of heroin a day, and a bag is typically a 100 milligrams, that they would take eight milligrams, and if they're using a bundle and a half, they take 12. It's so individualized, there's no specific, if you're taking this amount you need this amount of buprenorphine. It's really working out with the patients, but I can tell you that the majority of people are going to stabilize in terms of withdrawal symptoms on eight to 12 milligrams. So people that are using high amounts, I might go ahead and have them expect to be on 12 milligrams a day, where it's people that maybe are caught out on their opioids and never were an injection drug user, there's reason to believe that they could do well on a lower dose, I would start with eight. You reach a steady state within five days. So we typically then hold them at whatever dose you got them started with, and they may call and say "Two, three days into it, I'm having some withdrawal symptoms late in a day. Can I go up in the dose?" I will tell them or ask them, "How is it today compared to yesterday?" Often they'll say, "Well, it's a little better today, but it's still there," and I'll say, "Your body is reaching a steady state. It's going to get better tomorrow and the day after that." People will stabilize on eight to 12 milligram dose. They will stabilize. The reason we go up on the dose, and I repeat this, the reason that we go up on the dose is to reduce cravings, to stop their use of illicit opioids, to gain control over their opioid use disorder. That's why we're giving it. They will stabilize on any of these doses. I mean, stabilized in terms of withdrawal symptoms. The question is do they still have tremendous yearning to use an opioid? That's why we go up on the dose. We want to satiate their thirst. It's just like a drink of water. If you don't drink much then in a short time, you're going to still be thirsty. You want to satiate that thirst so your brain no longer goes to that place of I need a drink of water, and that's what we're trying to control with treatment to reduce that thought of I need an opioid. Again, the majority of patients are going to have that significant reduction, almost complete elimination of any cravings dosing between eight to 16 milligrams. If they do have withdrawal, significant after the first dose, I will tell you that it's typically only seen in the first couple of hours, then obviously the natural spontaneous withdrawal that was taking place before giving buprenorphine, will happen because there are obviously getting further and further away from the time in which they took and that lifted opioids, and they will stop at a certain level because now you've started buprenorphine. So in many ways it's just reassuring the patient, your experience is going to subside. At the same time, then if it stops getting any worse and they're still in mild withdrawal, that would be the time that you would give a follow-up dose and try to stop them from experiencing any further withdrawal and stabilize their symptoms. Again, if you give too much too quick then it's taking whatever opioids are still on, opiate receptors within the body and dropping it to their buprenorphine level, and in many people, even if they're in mild withdrawal, are going to experience some withdrawal symptoms. So again, I've said it a few times, start low and go slow. If you precipitate significant withdrawal, you can try to stop it from getting any worse by giving buprenorphine. But again, I would give it some time. If it's too severe, potentially they could go home, but I can tell you that this really doesn't happen. They are going to reach that place of stabilization, and once buprenorphine is onboard, they have buprenorphine onboard. They're not going to go to zero. They're not going to get in severe profound withdrawal like they would be three to five days after stopping an opioid. So again, we can stabilize patients with this treatment and it's extremely important. If you send them home, their potential for using that day is profound. This is some of the reasoning behind, some of the work that's being done now in emergency rooms around the country. Patient comes in overdosed or insignificant withdrawal, and we treat them symptomatically and send them out the door. We're not really treating them. We need to try to stabilize the disease. Home inductions, very similar to what I just described to you. But you're essentially teaching the patient about these principles so that they can do it at home. I will also point out that there's many of you have probably experienced in your communities, people are using medication on the street typically to control their symptoms for a period of time while they are either trying to go to work or trying to do other things, or they're looking for treatment, they're looking to get into treatment. So most of those patients we can treat very effectively with buprenorphine because they initiated at home, because they have a modicum of understanding. However, we know a lot more about the medicine and I've heard all sorts of lives tales from patients. So to go through these instructions very clearly with them is important. Then they really know more about the medications that they're taking and how to take in most appropriately. So again, you teach them about how it works, and how it's absorbed, and how to take it appropriately. Talk to them about establishing this mild-to-moderate withdrawal, and typically administering two milligram tablets at home. So again, they have less tendency to take a bunch of it at once and make themselves sick or go into a worsening withdrawal. Again, the typical dose is 8-12 milligrams the first day. Day 2, encourage the patient to preferably take the dose that they established on Day 1, the morning of Day 2. I typically will either call myself or have someone in the office call to just see that things are okay, and that they don't have any complaints or problems or questions. Then typically, if they've felt pretty good, again, except and even preface with them that they could have some mild withdrawal as they're reaching a steady state, and this is only going to get better. So encouraged them and we do a little motivational work and help them really think about getting in to a state of recovery and living their lives. This is a place where they're motivated. So they have some motivation to decrease their opioid use. So they're willing to tolerate just a little discomfort because most of them have been in a lot more discomfort at periods of time when they couldn't get drug in the past. So they tolerate this quite well. So you're talking to them either in person if you're doing an in-office induction, and I would encourage many of you to do this. That is, as the patient come back the next day, talk to them about what went on. See what level of symptoms or withdrawal they really are experiencing so that then when you do start doing more home inductions, you've seen it, you've talked to them, you have a good sense of what kind of problems they might be experiencing and how to help them. If they are having significant craving or they use an opioid on top of that and that sort of thing, I would go ahead and start increasing the dose. But again, most of the time I try to hold them to that first day. Encouraging them to recognize withdrawal symptoms are going to settle down so that then I have more option to go up if there's more craving after that five-day period. You want to stabilize for the most part between eight and 16 milligrams. There are some that encourage going higher on the dose, but I typically do not see that particularly if you're helping them think about moving forward in their lives and changing people, places, and things associated with cognitive behavioral treatments that we use to reduce cravings. So what are they doing along with the medication and typically I find that patients rarely need to go out above 16 milligrams. For the most part, the only patients I have on greater than 16 milligrams are patients that are having a combination of opiate use disorder and pain, and they split the dose as we've talked about to increase the potential analgesia that one would gain from settling on buprenorphine. Part of the reason for that is to reduce diversion, which we've talked about. So if you talk to patients that have taken it on the street, most of the time they're taking one eight-milligram tablet or strip a day with the other product, but one, they're not spending a lot of money on keeping themselves stabilized and they know they can't. So just keep in mind many times patients if they're on higher doses, they're going to recognize relatively soon. They don't need 24 milligrams to keep themselves out of withdrawal, so they have one or two of these medications that potentially could be diverted to the street. All right, so when we look at dosing and adjusting dose, I've mentioned some of these, but we'll go into a little more detail. So you want to continue to assure the patient about the value of making some changes in their lives while they're taking their medication. Then if there are problems with the medicine, go over again. How are they taking it? What time of day? Are they holding it under their tongue or keeping it in their mouth long enough to absorb all the medicine? There's no problem with taking it twice a day, or just splitting the dose. I just encourage patients to recognize this dose [inaudible] long half-life and it has slow dissociation from the opiate receptor in a way that they shouldn't have to take it more than once a day. But it's not a problem if they choose to. If they are going to be taking more than two strips or two pills a day, then it should be done in this split dose. So you don't put three tablets in your mouth at the same time. Then if there are problems, we typically then are going up by two to four milligrams and the famous two when we start to taper down. So we typically come down by two milligrams at a time. Patients typically tolerate that very well. Typically, if you're going up by two milligrams, there's not going to be significant sedation or other side effects by titrating it up. So how long? What we know is that patients taking this medication on a regular basis, increases retention and treatment. Retention and treatment is a primary outcome that it's really one of the mainstays of identifying that a particular treatment works. If people stay in treatment and that is, continue to take their medication, in this example, they are going to do better. Typically 16 weeks has not been highly effective in terms of people really turning their lives around, helping to change those people, places and things. Maybe getting control of various physical problems, social problems, and mental health problems. So to really establish a significant change in the brain in terms of this disease, we're looking at periods of time greater than 16 weeks. I will tell you that many patients will come in saying, "I don't want to be on this a long time." I've had parents come in with young people, then we want them off this medicine. I had one young man that I took care of that, was graduating high school, and they wanted him off before he went to college. By the end of the summer, they were like, "Dr. Wyatt, if he comes home during this first semester, would that be possible? Because they just saw such dramatic changes in him, and he wanted to stay on it and they were much more comfortable with it at that time." So patients will get to that place where they know it's helping them stabilize and move their lives forward in very positive ways. So the idea that somehow they're going to stop this prematurely for no good reason. Quite honestly, there's no good evidence, but stopping it prematurely is of any value in terms of helping them in their recovery. So as long as it's benefiting them, I would encourage them to stay on the medication now, as their cravings come down, as they stabilize various triggers to their disease to start talking to them about potentially coming down on the dose, it's fine. That's typically what I tell patients. They're not going to feel much different coming down on the dose, and it will maintain their cravings. [inaudible] But when they stop it is up to them. So here's one study really identifying that at one to three months, the recovery rate is not good. Three to five months, better but still not as good as continuous use. Patients if they stay in treatment, they get further and further along in stabilizing their disease and stabilizing other areas in their lives, important biopsychosocial areas of their lives. Here this was a study by David Fiellin, it's similar to a study done in the early 2000s by Kakko, where we see a significant difference in terms of retention and treatment by continuing medication as opposed to papering over a shorter period of time. Again to keep in mind that this is a lethal disease. So in the Kakko study, four of the patients that tapered off the medication, died over the one-year period that the study was going on. Died of an overdose. So again, we were helping to keep people alive and at the same time, helping them to have a down-regulation of any desire to use drug. So consequently, they are starting to do other things. They start to take care of themselves in other ways. Sometimes it's baby steps. Sometimes you see just profoundly wonderful changes in people. This is a highly rewarding opportunity to help patients. So then if in fact you are going to do medically supervised withdrawal, so withdrawal management using buprenorphine, you can do it very effectively. I again would only be doing this if you were looking at starting them on other forms of medication for addiction like naltrexone. But you can taper them down in any fashion. I worked at a substitute treatment program in Connecticut for a number of years, and when buprenorphine first became available, we did a five-day detox. So we would start them on 8-12 milligrams the first day, 12 to 16 the second day, and then taper down by four milligrams a day so they were on. There's protocols to go to just six milligrams and then four and two. There's all different ways. If they're not on buprenorphine for a long time, there's lots of that prolonged withdrawal that people can experience after they've been on buprenorphine for months or years. So it does work quite effectively in grabbing the receptors and then tapering them off rather effectively. So again, it can be short periods of time or much longer periods of time. If you are going to be starting on Naltrexone, it could be a little different and that's where to be thinking about nonopioid withdrawal programs like Clonidine that was just pointed out in the last slide maybe important, and we're going to go through that. So the long-acting injectable Naltrexone is now covered by many insurance companies. It does need to be ordered through a specialty pharmacy, and then it's typically shipped to the physician, and needs to be kept refrigerated until about 45 minutes or so before it's injected. So these are logistics that you would need to work out with the patient, but there's some nice programs for the patient and the physician to coordinate this, that through the company that provides this medication. You do clearly want to have the patient be opioid free prior to the injection and we're going to go through that protocol. You may want to do a Naloxone challenge to be very clear that there's no evidence withdrawal or that there's not still some opioid on board, and because Naltrexone will block at all. So anything that's there, any level above zero, they're going to potentially have some withdrawal symptoms. If you do challenge, then you can go ahead and give the injection after the Naloxone challenge. To be clear, if there have other pain problems, this would preclude down from getting much effect from most or all opioids. We can override it with various means but typically under medical supervision. People will sometimes report some headache though usually it's short-lived. It usually has to do with this change over from being on a lagginess to an antagonist, nausea, obviously and flu-like symptoms associated with the potential withdraw. But sometimes they will experience a prolonged absence feel that can cause some nausea over the first month or so of their injection. I haven't had too much difficulty in that way but I have added and again, very mild and typically left with subsequent injections. Probably, the most important thing that a lot of patients now is that you can get some soreness over the injection site. Once whoever's administering the medication, nursing typically really learned how to do it most effectively, there's less and less with this problem. That is it needs to be given in the upper outer quadrant of the buttock and the gluteal muscle, and it needs to be given deep IM. If it's administered within the fat, there's much greater chance of in duration and there have been some reports of actual observation and that thing. But typically, if it's given appropriately, they may have 12-24 hours of soreness but then typically it goes away. A number of patients really don't report much in the way of soreness at all. The Naloxone challenge, this is giving a short acting opioid antagonist that's often used most frequently to reverse overdose and most of you know the various ways in which we're trying to get this out into the field and be more available with first responders. Independent individuals, Naloxone will precipitate withdrawal. So if someone just took opioids for the first time and then got Naloxone, it would just block the effect of the opioids. They wouldn't go into withdrawal because the body had these transformations to chronic use of an opioid. But the withdrawal happens quite rapidly and then typically dissipates over 30-40 minutes, and that's part of the reason why we need to monitor patients after an overdose because once the Naloxone is gone, if there's still opioid in system, they can go back into an overdose state. So again, you can potentially measure the degree of withdrawal that they may have had. Usually you're really just trying to establish whether there's any withdrawal at all. We want them to not experience withdrawal because then that clearly shows that there's been a long enough time without an opioid, that they're clear of that. So by then initiating Naltrexone, we either orally or by injection, they're not going to have withdrawal symptoms because that's not short acting. It's not going to go away in 30 minutes, it's going to be there for awhile and it's very uncomfortable. So initiating the medication. So Naloxone isn't an opioid receptor antagonist that we've reviewed earlier in the modules and can be started in individuals who are completely free of opioids. So more rapid Naltrexone initiation methods using low dose Naltrexone can be affected. We sometimes will give small doses of oral Naltrexone to try to push more of the opioid receptors out of the system and then titrate up on that prior to starting the medication. So we want to have at least seven to 10 days with the patient being free of opioids and that is since their last dose. In this way, and I'm going to go through this in a moment, but you may want to consider not using buprenorphine or methadone as the withdrawal technique because it would be seven to 10 days after those medicines were administered before you could start Naltrexone. So to use a non-opioid type withdrawal is commonly done. So when patients are given Naltrexone and are still physically dependent, it would displace them all and you would precipitate withdrawal. So that's what we're trying to establish a state of stability following full withdrawal from opioids before we would start Naltrexone. So there's a variety of ways in which we would attempt to help patients with this withdraw. One is symptomatic treatment, and that's really what I'm suggesting and that is using non-opioid medications. So from the day you start this treatment, it starts the seven to 10 day period prior to giving Naltrexone or you can do more math rapidly, supervised withdrawal and that sometimes is starting to add Naltrexone along with symptomatic relief to just push this a little faster and getting people into a full withdrawal state more quickly. So I will say that I will sometimes have patients that maybe did taper off their buprenorphine. They want to have this as interim period following being on buprenorphine or any other opioids. So they paper down and now they are using Clonidine for three, four days potentially and then I start to have them use Naltrexone. We have them take a 50 milligram tablet, break it in half, and then break one of the halfs in half and take 12.5 milligrams for two days and then 25 milligrams per day and then they can take a 50 milligram tablet. If they have no withdrawal symptoms on 50 milligrams, then they can continue the 50 milligrams or you can feel comfortable going ahead and initiating the first dose of long-acting injectable Naltrexone. They'll have then these ultra rapid withdrawal protocols in the past under anesthesia. I don't know of any places till using this in a country any longer, there were a couple of deaths from anesthesia. It's just that there's no reason to put patients at risk in that way. So the symptomatic relief that you're giving is for anxiety and that is using an alpha-2 agonist. So it decreases the release of Norepinephrine within the synapse and that's typically clonidine and then you can help them with sleep with either Trazadone or really anti-cholinergics. I'm not a big fan of using Seroquel or quetiapine. It is an anti-psychotic medication. Very powerful. I've actually had some young people abuse quetiapine but I'm not a fan of that and I wouldn't encourage you. That's very expensive. There's typically not a reason to go to that degree of helping people with insomnia. Any musculoskeletal pain typically it's helped significantly with ibuprofen and is what I more frequently use. Then whether they are having GI distress, you can give them some hydration with just increasing their fluids and then potentially ondansetron to help with nausea and loperamide for antidiarrheal affects. If they're coming off slowly on and you're helping them, particularly with clonidine, we don't typically see this too severely. Again, they've tapered down on what other opioid that they were on and so the severity of their withdrawal is reduced significantly. So anti-cholinergics, excuse me, alpha-2 agonists. One thing is certainly, this is a blood pressure medicine also. So you want to be careful about instructing them that they could have some reduction in their blood pressure potentially orthostatic hypotension on standing too quickly. So I'll tell patients when you're getting up from lying down, sit on the side of the bed for a moment, just make sure that you're feeling okay. They typically, I don't hear too much in the way of these sorts of side effects. We start with 0.1 milligrams every six hours to 0.2 milligrams. I often will say 0.1 three times a day and then 0.2 milligrams at bedtime. Quite honestly, it can be sedating enough that it actually helps people fall asleep and so they're more comfortable than in the evening when they're up and around and doing some thing, doing things, their mind is off this more and they typically do well on just at 0.1 milligram tablet. Again, I really encourage hydration, try to stay well-hydrated during this period of time and then just symptomatically helping them with any other symptoms that they might be experiencing. People can have a flu-like experience. Mostly it's withdrawal experience, but it can be this low level, what's referred to as an Naltrexone flu typically on during the first month, though not extremely common but can happen. Just tell people about it. Tell them that this typically is not going to last into the second or third dose of the medicine and it's not severe. But if you just don't feel great on a daily basis, that can be certainly upsetting. But the more that people understand that this is getting the opioids out of their system, their system is adjusting to a non-opioid state and it may take some time. So you can alleviate some of those symptoms with medications that I just reviewed symptomatically with particular patients and most of the time these symptoms are going to remit over the first few weeks that the patient started on the medication and not typically in the second and subsequent dosing. Some predictors of withdrawal severity have to do with how much a patient was actually using in terms of opiate dosing prior to starting the medicine, how rapidly they withdrew from it. So they are still going to have some capturing of the receptor and just changes and not allowing the body to sort of compensate for the reduction in opioids over time. So the body starts to stabilize more that it can be the type of opioid that was being used, how much and what pattern it was being done. Also again, inconsistent use actually creates more of a problem. So many times heroin dependent patients that are injecting drug users, they're using different doses, different time sequences, that sort of thing, can actually upset the system in a way that it can take a little longer for the system to settle down to then be stabilized in a way that when starting Naltrexone they're more comfortable. Some patients will have more difficulty maintaining that opioid free period and that's the thing that we see most frequently and really separates this treatment from agonist treatment with either buprenorphine or methadone. You start those medicines people typically will initially have pretty decent retention and treatment compared to the first week to 10 days trying to get people to stop entirely so that they can start on the Naltrexone is the problem period. What separates it and has separated in some recent studies from the efficacy of buprenorphine and methadone. So in summary, effective suppression of withdrawal is important, and really, essential to the success because if you started too soon and they get sick and they just don't like it, they made afraid something like that's going to happen again and that sort of thing and it can be a real problem. You want to balance the degree of discomfort and the duration of treatment. Again, use symptomatic medications to help balance that and help them with any difficulties that they might experience. So it's the ability of the team to expect and response to these emerging complications and really be enthusiastic about the fact that it's not going to get terrible and it's also going to dissipate over time. So you just help the patients get through it more reasonably. Then anticipatory guidance, in that way, can be motivating for the patient to recognize and don't have greater insight. So what will happen if they maintain on the medication over a long period of time and really move their lives forward in a much more positive way. Let's now turn to drug testing and what things that you want to be aware of. This is a cursory exposure to drug testing, but it opens the door to your exploring a variety of things around how you would do drug testing in your own office and what testing you would want to do or feel comfortable doing. So it is important that you use drug testing. It can help you have a much better idea as to where the patient's at, what other drugs they might be using, and just gives you more clinical insight. What this is pointing out is this is not to catch patients. We're not police officers. I tell patients that this helps them and I have this place of honesty in some way. I'm not typically going to kick people out of program. I don't have to kick people out of program. I may eventually refer them to a higher level of care because of the difficulties that they're experiencing in terms of maintaining the goal, moving towards the goal that they establish when we started treatments. So if they're not able to stop other drugs, then we may need to look at a higher level of care. But again, this is to help them move towards their goal. That's not our goal, it's their goal. If they're not getting there, then we, in some ways, failed them or this level of care just isn't working for them in a way that they're going to meet their goal. So we talk to patients about that. At that point, there can be this place where, all of a sudden, they no longer have any cocaine or even more frequently marijuana in their system, and at the point of them saying, wow, yeah, I did it. I finally got that out of my system. So you can share in that place where people are really moving their lives forward in terms of less reliance on drugs for any form of comfort that they might have formally been experiencing. So laboratory testing, you need to establish with patients and the initial assessment that you're going to be doing this, that it's part of the treatment plan that you're screening for non-prescribed substances, you're monitoring adherence to what you are giving them. So we get buprenorphine levels and norbuprenorphine levels and evaluating them the efficacy of the treatment that you're providing now either done randomly or at the point that they come into program. I typically will always get drug screens when patients come to see me. I'm doing them once a week, that is radioimmunoassay testing, point-of-care testing, to see what they might be using or not using. Then as that stabilizes, I might spread that out. On the other hand, if they continue to have problems, I may add to that some random drug testing to just really establish more of a check for them. So they have it in their mind that I might be calling them and they might need to be come in tomorrow to get a drug screen. Then that way, you're using the drug screening to help them which reminder this feeling that they might have to come in. So again, you're using it therapeutically. Most effective or observed, although they can be difficult to do and so many places do not do observe urines. But clearly, it does allow for the greatest potential that patients are going to do well or give you an honest sample. You want to make it somewhat convenient for patients which can be very difficult to get them to come in for randoms, when there's work, and then transportation issues and things like that. You wanted a high-quality where it's trustable so that you can feel confident about the results that you're getting. There are various ways in which we do drug testing, so there's breathalyzers for alcohol. We can get blood levels. Not typically do we use this because the clearance is significant. Oral fluids, the clearance is also pretty fast, but saliva methods are being used in many settings, often more random than routine because, again, it doesn't pick up medications or other drugs for any long period of time. Urine, on the other hand, can be sustained depending on what drug it is, but at least, typically a few days at least. Sweat, again, doesn't get into the system very quickly but stays for a longer period of time. Here, also, it doesn't get into the hair in quantities that are easily detected for awhile but then stay in the hair follicle for as long as it hasn't been cut during the period of time that patients using drugs. So these are often used by courts and other entities to see what might have been in the system over a longer period of time. We have screening tests, and I mentioned this in radioimmunoassays that we're looking at. These are typically you're cops and point-of-care testing. Then they're not confirmatory tests. So we don't know what opioid it might be. There's less specificity to it. So that's when you go ahead and get confirmatory tests. Most places we would get confirmatory tests early to just get a general screening of what a patient might have been taking because they're going to pick up more drugs. Then just randomly after that, unless we continue to get opioids that we can identify, or there's concern about benzodiazepines that we want to clarify that we're not seeing a benzodiazepine, or amphetamine, or opioid that's not going to be well identified by the radioimmunoassay. We'll do something similar with buprenorphine. So you can get buprenorphine levels. There's not a radioimmunoassay or norbuprenorphine which would really show you that they actually took the medicine. They didn't just put medicine into their tox screen. We can tell some by the levels of buprenorphine within the system. So you'd test for a panel, typically in the office screening task, and then send confirmatories for any positive results to really find out what it is that they were taking. But these are expensive and so we do not do them in every time we get a tox screen. Point-of-care testing is way less expensive and not necessary. The common ways, the common things that we look for opioids, you can have cops that will have buprenorphine but buprenorphine, fentanyl, oxycodone, methadone are not going to be picked up as an opiate. You need to be aware of that. So if you're looking for those so you have concern about those, you would need to get confirmatory tests. There are tests now for fentanyl, essay tests along with buprenorphine, benzodiazepines, there's a fair amount of variability of what you're going to be establishing looking at benzodiazepine. Cannabinoids, again, need to be aware of the fact that if a patient has been free of cannabinoids for a period of time, if they then have a positive cannabinoid, it will typically only last a few days. It's after a person has been using cannabinoids for a long period of time that then it takes a long time for it to get out of the system. So you need to understand some of these things as you're working with patients. Cocaine, not much in the way of cross-reactivity. If they've got cocaine in their system, they typically have had the exposure to cocaine. So these are things that you'll learn. There's an appendices that's going to be available to you. It's at the end. I'll show you those, but we're not going to review them today. Testing for buprenorphine is really very important and I really encourage you to taste for buprenorphine. They can't hurt hard. Just rub their fingers inside a film strip and put it in their urine and it will test positive for buprenorphine. Then that way getting norbuprenorphine levels can be very helpful. It doesn't necessarily show you if you get a confirmatory test. It doesn't matter on the quantity that is they're taking eight or 16. It's not hugely different, but it's typically consistent between patients. So if you're seeing consistent ratios of buprenorphine, they'll axon with a specific patient over time and it changes dramatically, now, there's a high level buprenorphine and very little norbuprenorphine. You can rest assured that they hadn't taken it for a couple of days and now they just took it yesterday or even the day of the tox screen. So it's those sorts of variability that you can see in working with drug testing over a period of time that can help you clinically start being able to talk to patients more effectively. So in terms of authenticity of the urine, people can add substances to try to adulterate the urine, diluting with water and provide a sample for someone else. These, again, if you're open with a patient that you're not going to just kick them out if they have a problem, and what is their goal? And are you watching their biopsychosocial lives move forward, you don't have to be terribly worried that everyone's going to have a clandestine urine. We do test for creatinine levels, you test for temperature. These actually can come on the cups that you use. So you can just see that right away. Certainly it can be picked, these products can be picked up as abnormalities if you send them for confirmatory testing. So just to be aware of the fact that temperature, specific gravity can give you some good evidence that this is not the patient's natural urine. Then in some way it's been tampered with. Inconsistent results. You should establish what the plan will be if they continue to have positive tox screens before you start, what's our goal? Where are we going to go with this? So that then you can fall back on that and say we're not reaching the goal. I've said that a few times now, but I find it extremely important to help them understand we're not moving in the right direction. There's continued problems when you're not getting what you wanted out of this treatment. Then think about other ways in which you could be helpful. Maybe continuing them on buprenorphine, but referring them to other services that could help them move forward and that sort of thing. But it is important to establish this at the time that you're initiating treatment. Then when you get the results you're discussing with the patient. So rationale behind it to certainly review these results, show them the results, and then think about other things that can happen. I mean, there is truth to the fact that they either, even a poppy seed bagel, they could have a positive opioid. But you can find that out through confirmatory testing and just discussing it with patients and the importance of not eating obviously bagels. Then reestablishing what are the goals with the patient. Where are we moving with this? How can you get other illicit drugs out of your system? Typically, if people are using something else during the time that they're taking buprenorphine, they all are thinking they're going to be off. That's pretty much all of them someday, and if they continued to be using other drugs, they're setting themselves up for having a potential relapse on their drug of choice, which is typically opioids at the point that they would stop treatment. So again, we want to really be thinking about how are we really moving patients forward. Frequency really has to do with how the patient is stabilizing. So again, I keep people typically on one week prescription. So it's somewhat of a contingency management, there one week scripts they're getting weekly tox screens that leads and until that's clear and we've started to move forward, then I will move them into less frequent of both prescriptions and drug-testing. So it really depends on the stability of the patient, to a degree the half-life of the medication or the drug that they're exposed to. But we're most concerned about daily use of drugs, and so if it's a pathetic use, and they're moving forward and you're not picking it up, we're not police officers. We just want to see people getting healthier. So it may depend partly on what the treatment center setting you're in and how you're doing this. But for the most part for office-based, that'll be a treatment you're doing urine tox screens. Randoms can be helpful, but again can be very difficult for patients, can be somewhat difficult for us. Creates some confrontation at times. But people living in smaller communities, a community which I had formerly lived in, most people live there and so it was easier to call them in compared to living in a larger city where it's more difficult to get patients in and randomly. Typically, we're doing this with a local laboratory. So you want to fully understand what methods the laboratory is using, liquid chromatography, gas chromatography, what are you getting out of their form? A lot of these companies will give you a lot of great information. They'll grab things over time. They want to be helpful in that way. You want to know what they're screening for and the sensitivity of those tests, what are the cut-off levels and have a good idea about the personnel that you're working with and so I don't always do this, but I have certainly over time had reason to talk to the lab and introduce yourself and then they get a sense that you're really interested in what's going on. It can be very insightful. They can give you some really good information. So in summary, in total, induction is best initiated with a patient is in mild-to-moderate withdrawal that's 8-10, 11 greater than 10 and there's a chance that you would precipitate withdrawal if they're not already in the spontaneous level of withdrawal. But at the same time, if you start at a low dose and go up slowly, you're not going to get into too much trouble. There are therapeutic dose of Buprenorphine is that dose that manages cravings most effectively. It's not typically withdrawal, typically withdrawal symptoms are going to stabilize. That's not a reason to go up on the dose, it is if they continued to have a strong desire to use drug or continue to use drug and that would be a reason to go back. Extended release Naltrexone provide a non-opiate alternatives to medication-assisted treatment and it's clearly identified efficacy and tolerability with patients over time. Drug testing is a very important part of office-based opioid treatment. So you need to know about it. You need to know what your tests are identifying both in the office and then whatever the lab you might be using for confirmatory testing and then how long certain drugs will stay in the system and those sorts of things so that you can interpret the test most effectively. You have a variety of references as you've seen in the other modules and these are dependencies. You have access to these but the explanation around amino acid and chromatography spectometry. How long the these different drugs stay in the system. Things that you can look at in terms of identifying the authenticity of a specific urine specimen. In terms of looking at what are the agreements with the patient around drug testing and how you're going to potentially approach problems that might arise with various drug testing and then as the amount of drug testing as per the stage of treatment that the patient's in. So the stage of recovery that they might find themselves in and then looking at what happens with various false positives. Why did they show up? There's a whole host of tables available, some of which are available on the PCSS website. Looking at these cross-reactivity that you could at least look at if the patient is insistent that they have not used any illicit drugs. Again, cocaine is really quite specific and so you're pretty hard-pressed to let that one go. Here's some of the example of some of the other false positives. Again, poppy seeds can show up as opioids. So you want to review that before you start and then if they do come up as these, we talked about this, you need to stay away from ingestion of poppy seeds or it will constitute tox screen to be positive and then we have to go through with this and here's just an outline in terms of the breakdown metabolism of heroin and how it can show up in various ways and then just the idea that oxycodone it's not going to be picked up by a standard opioid Immunoassay testing and more breakdown of opioids and how you might see a certain product come up as per the breakdown like codeine. At the same time, the synthetics, you need to be looking for specific synthetics over time. Then similar with Benzodiazepines, most of the benzodiazepine screening tools are looking at diazepam breakdown and so strangely enough, a couple of medications that are most frequently prescribed like Alprazolam and Lorazepam are not typically going to be picked up because they don't break down to oxazepam and so strange because again, Clonazepam, Alprazolam and Lorazepam are probably the most frequently proper prescribed Benzodiazepines and they're not easily picked up on radio-immunoassay testing or immunoassay testing. All right, that concludes this module. Again, I encourage you to take a look at the PCSS website, there is a lot of educational materials there. There's other training opportunities and mentoring available to you and with that, I can say goodbye.
