Hello, my name is Melissa Wymer, and I will be talking to you today about opioid risk assessment, mitigation, and management. This is a lecture part of the PCFSO core curriculum for pain. This is a lecture co-written by Dr. Dan Alford, Dr. Philip Coffin, and myself. Our objectives today are to describe universal precautions and their role in opioid therapy, review monitoring and documentation strategies for opioid therapy, explain the fundamental principles of urine drug testing and interpretation, list the differential diagnosis for aberrant drug-related behavior, and describe when naloxone co-prescription should be considered. Let's start off with a case. So you're seeing a 45-year-old man with hypertension, heart failure, and tobacco use who's been prescribed high-dose opioids for chronic, nonspecific testicular pain after a vasectomy 15 years ago. He also has mechanical low back pain. You're seeing him for the first time after his previous PCP retired. His current total morphine equivalent dose prescribed is 390 mg per day. He's also prescribed Valium 5 mg BID for muscle spasms. Prior medical records are sparse. Review of the prescription drug monitoring program shows several early prescriptions over the last three months from his cardiologist who has agreed to prescribe for him while he found a new primary care provider. And tells you that he has a history, a family history of alcoholism, and a personal history of gambling use disorder or gambling addiction. We'll come back to this case as we review our slides. So when we're thinking about how to approach risk management and mitigation, we really need to think about it in terms of universal precautions. And the reason we need to think of this as universal precautions, like we would for washing our hands or doing other things in healthcare, is because predicting opioid misuse is imprecise. We don't have specific ways that we can say, this person will absolutely develop a problem with their opioids. And in this way, we're protecting all patients, we're protecting the public and community health. Also, if we apply these precautions universally, we're taking the pressure off the provider. And we're reducing stigmatization of individual patients, and we're really standardizing a system of care. This is resonant with many of the guidelines that are out, the new CDC guideline, previous American Pain Society, American Academy of Pain Medicine, and others listed there. And this is really all part of an office-controlled substance policy that you might have in your clinical practice. And again, the reason we need to apply this universally is because, really, we now are beginning to know more about opioid use and how it may really lie on this continuum. We know that there are patients who have pain and are prescribed opioids, and we also know that there are patients who may use opioids for non-medical purposes, meaning other than for the reason that it's prescribed. And at any given time, a patient who has pain may be adherent, may, from time to time, do what we call chemically cope, which means they're taking the medication in relation to a feeling or an unpleasant feeling, anxiety, need to sleep. They may develop abuse type of behaviors, and they may actually develop an opioid use disorder or addiction at a certain point in time. And this can exist on a continuum where, at one point in time, they may be adherent, another point in time, they may have other behaviors. Same goes for patients who are using opioids for non-medical purposes, that they can exist on this continuum where, at one point in time, they might be treating or self-treating, and then their self-treatment may worsen and they may develop an opioid use disorder. Opioid misuse in primary care is likely under-recognized. I think we're starting to recognize this more with all of the attention that this topic has been getting, but when we first started thinking about this in the early 2000s, it was probably quite under-recognized. And at that time and since, really published rates of prescription opioid misuse have ranged in a primary care population anywhere from 4 to 26%, meaning that for all of the patient population who are prescribed opioids, we don't exactly know how many might be misusing. However, we think that there could be up to 26% of patients misusing opioids. And in one study that was done, a qualitative study that involved two-hour interviews with 801 patients who were prescribed opioids for pain in a primary care practice, they found that 26% admitted that they were, at times, using for sedation purposes, so to help them sleep or to help calm them down. 39% were increasing their dose of their opioids without their physician or provider allowing them to. 8% were obtaining from other providers. 18% were using for purposes other than pain, so that non-medical use. 20% were drinking alcohol to relieve pain in addition to their use of opioids. And 12% were hoarding their pain medications, potentially for fear of losing or being without their medication. So we know that patients can do multiple different things with their medication, and again, we can't look at someone and be able to say, this person might develop a problem due to their opioids. So again, we need to apply these precautions and how we prescribe across the board universally and make this part of a comprehensive pain assessment. And in so doing, we're saying that in order to fully treat someone's pain with an opioid, we need to have a comprehensive plan, and that plan needs to include an opioid risk assessment. Do we think this patient may develop a problem with opioids? Knowing that any patient who's prescribed opioids is at risk, but some patients may be at more risk. And part of this plan includes making sure we know what we're treating. So what is the painful condition that we are treating? We should also consider opioid prescriptions, a test, or a trial. We know that some patients will not benefit from these medications and could be at risk for severe consequences. So we really need to continually, part of our universal precautions, assess risk and benefits over time. And we need to make a decision of whether opioids should be continued or discontinued regularly with the patient actively involved to say, I think this medication could be harming you or I'm concerned that this medication is no longer safe. So when we're starting opioids, we're not saying this is a medication that you'll be taking lifelong. Instead, we're saying this is a test or a trial to see if you'll be benefited from this medicine. This involves regular face-to-face visits and clear documentation of what we're treating, why we're treating, and that the benefit outweighs the risk. Part of our universal precautions is also having, when we initiate treatment with opioids, a patient-prescriber agreement. This is also known as an informed consent where we're discussing goals and risks and a plan of care. So these two things are part of that patient-prescriber agreement. It's a document that's signed by both the patient and the prescriber, and I think it's really an opportunity to do really specific patient counseling. Its efficacy is not well established, but there's no evidence to suggest that it has a negative impact on patient outcomes. Part of what you're doing when you're going over this informed consent of plan of care is you're helping the patient understand what monitoring strategies you will put in place. So for instance, you are going to regularly monitor opiate adherence, you're going to regularly monitor for serious harm such as opiate use disorder or diversion, and you might perform urine drug testing, pill counts, and checking a prescription drug monitoring program. Part of the informed consent is also to establish goals and help the patient understand risks. So part of the goals that you're setting are to help the patient understand what is really realistic to expect from opioid treatment. We know that we can reduce pain in some patients with opioid medications, but it's quite unlikely we're going to eliminate pain. Additionally, we need to help the patient understand that ultimately the goal is really that we're improving functional status, and we need to know how to measure that. This is generally best measured with individualized, what we're calling SMART goals. SMART goals are specific, measurable, action-oriented, realistic, and time-sensitive goals. So an example of this might be a patient who is quite sedentary. Maybe their goal would be, I will walk around my block once a day for the next two weeks. Or I might walk to the mailbox twice a day for the next week. So it's something that's very specific, a specific activity, not something like, I will walk. Well, how are you going to walk, where are you going to walk, how are we going to measure that? So you really need to be very specific. You need to be able to measure it. It needs to be action-oriented, so something the patient will actually do. It needs to be realistic for the patient. If the patient has been quite sedentary, walking a mile is probably not a realistic goal. And then something that's time-sensitive, such as once a day. We talk about risks a lot in many of the other lectures, and I would encourage you to listen to those lectures, but patients need to be aware that there are several risks with opioids, including potential physical dependence, several drug interactions are potential that can have over sedation, there may be impairment with driving, the development of opioid use disorder or opioid overdose. Women who are pregnant need to know about the significant risk of neonatal abstinence syndrome. They need to know that potentially their pain could worsen over time, they could develop opioid-induced hyperalgesia, and that there could be potentially victimization by others who are seeking opioids, potentially if they're quite vulnerable, or living with someone who might have an opioid use disorder. The plan of care, and I would also encourage you to look at the ACP Quality Connect video listed here, so the plan of care, which is part of the agreement, will help engage the patient or start a conversation about what sort of engagement is needed with other recommended treatments such as physical therapy or other types of therapy. Patient needs to know what your policies are for monitoring their adherence for opioids, your refill policy, potentially obtaining permission to communicate with other people in their life if you're concerned about the use of opioids, really setting an expectation that there should be no illegal drug use and there should be avoidance of any sedatives such as benzodiazepines, letting them know that you may notify other providers of their medications or drug use if they're pregnant or at risk, or they should be on birth control and there might be periodic monitoring for pregnancy, letting the patient know that they need to use the medication as directed, there should be no alteration of the pills, patches, the schedule, let the patient know what they should do if they miss doses, things like that. Safe storage is a really important point to help patients understand that they need to keep the medication safe, typically in a lockbox somewhere away from family, visitors, pets, or children because there can be serious consequences if someone who's not used to these medicines take them. Safe disposal, if they no longer take the medicine and let the patient know that under no circumstances should they be sharing, selling their medicines and even for somebody in their family or a friend. When you're discussing monitoring, it's important that you review the personal and public health risks of opioid medications and so why we need to be very careful about how we prescribe. Your responsibility to look for early signs of harm, discuss the agreement, pill counts, drug testing, prescription drug monitoring as ways that you're going to help protect the patient from being harmed by opioid medications. You can use an analogy such as periodically checking renal function in a patient prescribed an ACE inhibitor or liver function tests in a patient prescribed a statin. And again, you're really going to use the very consistent approach for doing this across any of your patients who are prescribed opioids, but you're going to set your level of monitoring to match the patient's risk of being harmed either by an opioid use disorder or another harm. And we'll talk about how you determine that. Your role is not to be a police officer or a judge, rather you need to remain a provider and use a health-oriented risk-benefit framework. So you're not asking is the patient good or bad, does the patient deserve opioids, should this patient be punished or rewarded, should I trust the patient, rather you're asking the question, do the benefits of opioid treatment outweigh the untoward effects and risks for this patient or society? So you're judging the opioid treatment, not the patient. This is something we do throughout medicine all the time as far as judging whether it's safe for a patient to be on aspirin, safe for a patient to be on a statin medication, many other medicines and therapies that we utilize. So let's talk about how we might put universal precautions in practice. How do we determine the level of monitoring? I said that you're going to use a consistent approach and set the level of monitoring to match the risk for a harm. So really what we're talking about is for patients who are at higher risk, you're going to do more frequent monitoring, moderate risk, slightly less monitoring, and then for lower risk you're going to do less frequent monitoring. But what does that actually mean and what are some timeframes and how are you going to discuss this with your patient? So if you're thinking about risk and how you determine risk and how should it be used, well really we're using it to discuss our level of concern with the patient. If you have a patient who has very high risk, say in recovery from alcohol, you might say despite being in recovery from your alcoholism, you're at higher risk for developing problems with the opioid medication. So you need to let them know that you're aware there's higher risk, you're concerned that there may be higher risk, and it's something that you will need to monitor actively. You need to let the patient know to what level will you monitor and how should that be implemented. So you'll want to talk about the frequency of visits that you might ask them for, your drug testing frequency, all of those things. You may ask this patient to come back or agree to random callbacks. You may need to really strictly monitor pill counts and things like that and you may need to let the patient know that they might be asked to come into your office with 24 hours or 48 hour notice to come in for a pill count. You should be open with them that if you determine that there is a level that you're concerned about relapse or them developing a risk such as opioid use disorder that you may need the help of a pain or addiction consultant and ultimately if a patient has say an active substance use disorder or another type of a very serious risk, that patient may be too risky for an opioid analgesic and this is somebody that you need to let them know the risks outweigh the benefit. What are some different tools that you might use to determine risk for opioid misuse? Those are listed here. I can tell you that there's no gold standard and many of these tests lack rigorous testing but there are a few that we tend to find are a little bit more feasible in primary care and tend to have slightly better validation. The one that many people are using is the Opioid Risk Tool which was developed by Lynn Webster in 2006 in this publication listed here. If we think about this for the case that I presented, again reminding you this is a 45 year old man on high dose opioids, reports a family history of alcoholism and a personal history of gambling use disorder. For this patient, he would have a total score of 5 based on his family history of alcohol use disorder, his young age and his history of depression. He did receive a moderate risk score here you can see for somewhere because he's 5 which scores between 4 and 7. What the Opioid Risk Tool does not take into account and which is why I was saying that our risk tools are imprecise and potentially not always completely accurate is because we're not taking into account that he reports a personal history of a gambling problem which could signify that he potentially would have compulsive use of his medication or that he may be in a situation where he would need to divert his medications for income, does not take into account that he has had early refill requests, does not take into account that he's on a high dose of opioids, that he's prescribed a benzodiazepine concomitantly and that he appears to have apparent poor benefit of opioids because he's reporting very severe pain and he appears to have poor pain coping. So altogether, based on your risk tool assessment as well as the history that you've obtained, you can say that his risk is actually assessed to be quite high. So how would that change your management? Well, this would be a person you would say I think that he is at risk for developing severe consequences of his prescription potentially and so because of that I need to monitor him more closely. So I'm actually going to do 14 day prescriptions for this patient as opposed to a full one month at a time. I'm going to utilize urine drug testing more frequently, every one to two months. I'm periodically going to do random pill counts and I'm going to closely monitor the prescription drug monitoring program for his refills because he's had history of obtaining opioids from other providers and he has also had early refills. So here's a table that kind of shows you how you would approach monitoring for a low, medium or high risk patient. And I also want to refer you to the ACP Quality Connect chronic pain minimizing the risk of abuse video which goes through this in more depth. If you look here, sort of putting our patients into these different categories, low, medium and high risk, you'll see that as risk increases so does the frequency of your monitoring such that a patient who is low risk, if we're looking at say urine drug testing, is getting a random urine drug testing every 6 to 12 months as opposed to a patient with high risk which is getting this test done every few weeks to every month potentially. And you can see that all of the different measures here such as an agreement, the pain visit with a functional goal, the pill counts and the prescription refill allowance are getting much more strict as the risk increases. And again, this is an example of a monitoring approach. This does not mean that you have to follow this to a tee, but it's an example of how you might approach a patient with different risk categories. Okay, so let's talk about these monitoring strategies in more depth and we're really going to go into more depth about urine drug testing in this next section. I would also encourage you to look at the ACP Quality Connect chronic pain minimizing the risk of abuse video, which also talks about this topic. So for the office visits that you're doing for your patient, what are you actually monitoring? Well, an easy way to remember this is to think about the six A's. So you're going to monitor analgesia, activities or functional gain, adverse effects, aberrant behavior, adherence, and affect. So those are the six A's. Also, you want to review with the patient how they're using their opioids. Are they actually taking the medication as prescribed? You can describe this as a 24-hour inventory. Some patients may say, well, I actually end up taking eight of my tablets for the first 14 days and then I end up taking six a day because I don't want to run out. So you might find that your patients are altering their prescription differently than you had intended. You want to use objective information or obtain objective information. Are there any signs of medication misuse? Most severe sign would be does your patient have track marks or other stigmata of potentially opioid use disorder? You want to check the prescription drug monitoring program, which can provide really important data. Performing urine drug testing. If you have access to point of care urine drug testing, that might be less expensive and give you more rapid information. Pill counts if indicated. And then revising your treatment as indicated based on these results. Alright, let's spend the next few minutes talking about urine drug testing, which can be quite an involved process and actually there's quite a lot to know about urine drug testing. So we're going to go into this more in depth. So why are we doing this? Well, we're doing it because it can provide objective information about therapeutic adherence and evidence of use or non-use of illicit drugs. When you are ordering a urine drug test, it's important that you discuss with the patient that you are ordering it. I also many times will ask my patient if I have concerns. If I send your urine right now, what will I find in it? Many times they'll tell you, you know, I smoked marijuana or I drank last night or something like that. So many times they will tell you what you might find in the urine. It's important that you document the time of their last medication use. If they last used their prescribed opioid five days ago, it's possible that the test will be completely negative. If there's an unexpected result, you may need to do more of a random urine drug test. If the patient knows that they come in for a pain visit and they're going to have a urine drug test, they can know exactly how to either stop illicit use or take their medication. It is important to remember though that this is just one medical data point. It's not meant to be the only piece of information you're using. Really you need to integrate this with all of the other information that you're obtaining. It cannot discriminate between elective use, addictive use, or diversion many times unfortunately. There are risks of doing urine drug testing. Potentially the sample could be mislabeled. There could be adulteration of the sample. There could be other errors. If you're not sure how to interpret a result, it's important that you have a relationship with the toxicologist or clinical pathologist. They can help you with interpreting the results. If the patient wants to deceive you or beat the system, they will be able to beat the system if they're super dedicated to wanting to do that. It has its limitations and it does have its risks. Why we're doing it? We're doing it because self-reported drug use among patients with pain is unreliable unfortunately. Behavioral observations detect only some problems. We think that it may improve adherence such as decreasing illicit drug use. It really is an evolving standard of care part of opioid pain management monitoring. Some of the ways you might introduce this to a patient is you might say, as part of treating pain with opioids, I order urine drug tests to help me understand how safe they are for patients. The test measures a number of medications and drugs that could interfere with your treatment. This is something I do with all patients on these medications and it doesn't mean that I don't trust you. Again, part of the universal precautions. If I find something unexpected, we'll talk about it and work together to address it. I think that's an important message to give the patient that this is really about making sure you're safe with this medication and if this medication is harming you, we need to work together to find a better solution. Some nuts and bolts about urine drug testing. Urine drug screens. There are two parts of urine drug testing. There's screening and there's confirmation. The first part of a urine drug test is the screen. This is usually an immunoassay, an ELISA immunoassay. It can be done as a point of care test or it can also be done in a lab. It's a relatively quick and inexpensive test, particularly if done in the office. You really need to know what's included in the testing panel and some diagnostics of the testing because many of these tests are different. There can be risk of false negatives due to different cutoffs that a particular urine drug test has and then you actually can have a relatively high risk of false positives due to cross reactions from other medications. The main point is because this is a screen, really if there are unexpected findings we need to get the confirmation test, which is the gas chromatography mass spectroscopy test done to really help us determine what we're seeing on that screen. That is the most important point of really being able to determine what we're seeing on the screen, particularly if it's unexpected. The gas chromatography mass spectroscopy confirmation is going to identify the specific molecules that you're seeing on the screen. It's more sensitive and specific. It is definitely more expensive. You have to actually be aware of opioid metabolism in order to interpret it. We're going to go over that a little bit. It is important to note that many times with this confirmation, confirmatory testing, you are getting a urine drug level. This is not actually a valid method of determining the amount of opioid ingested. You might see a quite high level on your urine drug test, but this really can't tell us that the patient has overtaken their medication or it's just really not valid in that way. You can see here some of the metabolism for say heroin. We're going to go over this in the next few slides. Here's one graphic of the different opioid metabolic pathways. As you can see listed here, poppy seeds going to codeine and morphine, heroin going from the direct metabolite 6-acetylmorphine, which is only really active in the urine for 20 to 30 minutes, then going to morphine. Then you can see that there are lots of different metabolites of morphine and codeine. You can also see that aparidine, fentanyl, and methadone really are sitting out on the other side because they are synthetic and they are not typically picked up on our opiate screens. Here's another graphic to explain this differently showing that we have natural opiates and we have semi-synthetic opioids and all of these may be picked up on a urine drug test as an opiate. The caveat here being that oxycodone and oxymorphone is typically not picked up as an opiate on a urine drug screen. Our other, our synthetic opioids such as methadone, as I was saying, aparidine, and fentanyl are not picked up as opiates on a urine drug screen because they do not have the same, they're not made of the same derived of morphine and codeine. We do talk about this a little bit more in one of the other lectures that you may refer to. The typical detection time in the urine are listed here. We do have an appendix to this lecture that I would refer you to. Talking about this in general terms or just to highlight a few of the points on this slide is that marijuana, which can be a pretty hot topic when we're talking about opioids, can exist in the urine for several days. However, the length of time that it exists in the urine actually is dependent upon how much of a user the person is. So somebody with a single use, we think that marijuana is typically cleared in the urine after three days. However, somebody using on daily use, marijuana might be in the system for 10 to 15 days. If they're a chronic, heavy, long-term user, it may be that marijuana is existing in their body for, or their urine for greater than 30 days. Another slide about some of the potential harms of urine drug testing. We are potentially harming patients if we are incorrectly interpreting the urine drug test. This could result in adverse consequences such as unwarranted discontinuation of opioids. You could damage the provider-patient relationship in the process. There's the potential for false reassurance, meaning that if the patient was tampering the urine or altering because they're anticipating their urine drug testing coming up, this could give us false assurance that the patient is using their medication as prescribed when they actually are not. Really, we need more evidence to understand the effects of urine drug testing on patient outcomes, to understand how frequently it should be done, and how it should be done. So a lot of opportunity here to better understand this use in practice. A few other pearls to mention. I was mentioning that oxycodone and synthetic opioids do not show up as opiates on the urine drug test. This is an important point to know and remember so that you understand that if your patient is prescribed oxycodone and the opiate screen is not positive that that's actually an expected result. Methadone typically needs a specific methadone test in order to detect it. Oxycodone and oxymorphone need a specific test as well. Fentanyl needs a specific test. The new type of fentanyl that we're seeing come on the market. Carfentanil actually is not picked up on most urine drug screens. Certain drugs may cause false positives on screening, but not gas chromatography confirmation. If you have a positive amphetamine screen on your urine drug test and there's a question of effects or something such as that causing that false positive, when you do the gas chromatography confirmation, your amphetamine urine result would be negative. So that's why it's important that you're doing that extra confirmatory testing if there is an unexpected result. Benzodiazepines can be difficult to detect on certain urine drug screens and so you might actually get a false negative. If you're prescribed a benzo, it's not picked up on the urine drug screen. This would actually be an instance where you may perform a gas chromatography test on a negative result. When you do the gas chromatography test on that result, it would actually give you more information. So a lot to know here about urine drug testing. Again, another reason why it's important that if you get an unexpected result, you know who to call your toxicologist to get some more information. Even more depth here, just to sort of help walk you through the steps of how you're going to do this testing. Number one, you're going to anticipate what results do you expect from your test. You need to obviously identify which medications your patient is taking and then really think about what results you might find based on the test that you have. You need to know when the patient last took his or her medication and you need to document this information in your note. Step two is to select the appropriate test. The screening again is going to be the immunoassay. Are you going to look for an entire panel? Are you going to just look for individual drugs? Are you going to do point of care testing or laboratory testing? I know in my clinic I will sometimes get more false positives for my point of care testing and so I will sometimes need to send it to the lab to get a more accurate result. Confirmation, again that more expensive test. Are you going to automatically confirm all positive results? Are you going to confirm potentially negative results? How are you going to do this? It's important to work with your lab to kind of create some protocols to understand how to best do this for your population. Step three, you need to assess the specimen validity. Assess the color, the temperature. If the urine is cold, it's probably not a fresh sample. I know the MAs in my office are quite savvy at understanding when it's a cold urine or if it just looks funny, looks more like water. Patients may attempt to tamper by adding water or bleach or other types of agents. The pH range of the urine will help you determine if it's a valid sample. The range should be between 4.5 to 8.5. The creatinine concentration can be another way to determine if it's a valid sample. The creatinine concentration should be greater than 20 mg per deciliter. If it's less than that, it may be dilute. If it's less than 5, it may actually not be a human sample. It could potentially be from an animal or some other source. Then looking at the specific gravity as well. Step four is to compare to the expected results. Based on the medication that's prescribed, looking at what you expect to see on the immunoassay versus the confirmation. This is a helpful table to have access to that you can look at more in depth after the lecture. For the differential diagnosis, there is a differential diagnosis to know about for a urine test result. If it's positive and it was, say, unexpected, does that mean the patient is using non-prescribed medications? Are they using illicit drugs? Are they using previously prescribed medications due to hoarding? Is there some sort of cross-reaction, contamination, or laboratory error? If it's an unexpected negative result, does this mean that the patient could be diverting? They didn't take their medication within the time frame to make a positive test? Is the person potentially a fast metabolizer? Is there some sort of processing error? If the urine is very dilute, this could cause a false negative test, malabsorption, hoarding, or binging. Again, these false positive or negative results should only be occurring on the screen and not on the confirmatory test, with the exception of poppy seeds, which can come out with a confirmation positive for codeine. Talking about the patient that we were discussing earlier, this is a patient prescribed morphine, long-acting morphine, and diazepam. We would expect that he would have a urine screen result positive for opiates, because the morphine creates that positive opiate screen, and then potentially benzodiazepines, if our screen was able to pick that up. The confirmatory results you would expect would be positive morphine, potentially codeine, which is a metabolite of morphine, and then diazepam. This would be an expected result based on those prescribed medications. As you can see, codeine is not prescribed, but it's a potential metabolite of morphine, so this result actually means the patient is taking their medication as prescribed. They are not taking extra codeine. We're just seeing that metabolite in the urine. If your patient were prescribed oxycodone, what you would expect to see, again, if you have a urine drug test that is able to detect oxycodone, would be oxycodone and then positive benzodiazepine, if they're prescribed the benzo as well. You're not going to get a positive opiate screen for this patient, because oxycodone does not typically cause the opiate test to be positive. For the confirmatory testing, you would expect to see oxycodone, oxymorphone, and diazepam. The reason you're seeing oxymorphone is that that is a metabolite of oxycodone. Again, this doesn't mean the patient is taking oxymorphone that you did not prescribe. It means that they're taking oxycodone that you prescribed and the metabolite you're picking up on the confirmatory test is oxymorphone. Let's talk a little bit about pill counts. Pill counts can be objective information that can confirm medication adherence and potentially minimize diversion. Ways that you can do this or you can promote being able to track patient's prescription more easily is to do a 28-day supply rather than a 30-day supply. If you do a 28-day supply, that means that the medication will always be due on the same day. If you prescribe on a Tuesday, the patient will always be due on a Tuesday. It also helps make sure the patient's not ever going to be out on a weekend or need a prescription that way. You also may prescribe so that patients have some residual medication at the appointment so you can actually count the medication. This may be something that you do as part of your monitoring. Ask the patient to bring the medications at each visit. Really this helps to identify risks or concerns, but if you're really concerned you may need to ask the patient to come in for a random callback for immediate counts. Typically this is most effective if the patient is asked to come in within 24 hours. Prescription drug monitoring programs are an important way of monitoring risk. This is a statewide electronic database that typically tracks controlled substances. All states are slightly different, but by and large this is what's generally tracked. The prescription data is available to prescribers and pharmacists usually for the past year with information about the date dispense, the patient, prescriber, pharmacy, medicine, etc. We are finding in some states or some areas it's a substantially underutilized resource. I would encourage you to use it if you are prescribing opioids. Some states do have a mandate that you have to use it prior to writing a controlled substance. I know in my state does not. Several studies suggest that there could be an association between monitoring use and positive outcomes related to improving prescribing and reducing prescription drug abuse. There is some data emerging to show that these could be protective for patients. Again when you are discussing monitoring and you are thinking about how to do it, we are reviewing the personal and public health risks for opioid medications, discussing your responsibility to look for and manage early signs of harm, discussing agreements, pill counts, drug testing, all of these things as ways that you are helping to protect the patient from being harmed by medications and again we really want to use a consistent approach to this, use universal precautions but apply it individually to each patient to match the level of risk. This monitoring can be a lot of work so it's important to engage your office staff, help educate your staff on the protocols and policies. If your staff is not on board with this or is not able to help you, this can be quite time consuming so make sure you have some clinical policies among your clinic staff and your other providers of how and when prescriptions will be dispensed, appointment expectations, program expectations, thinking about how you might manage poorly controlled pain or if opioid use disorder is detected how you might manage that. Be consistent, sending the same message from staff and other providers is important. Really engaging the entire team to help educate patients, monitor patients, reminding patients of the policies and treatment agreements, managing the refills in a safe way and monitoring adherence. Okay, so let's talk a little bit now about if you detect in barren drug related behaviors how might you manage that. So let's think back to this case. The patient calls to request a refill 8 days early stating that his daughter is in the hospital in another state. He had actually been in the hospital for 3 days during his current prescription. So if you go back and you calculate, again based on this close monitoring you're doing you can see that the refill would actually be 11 days early. So an early refill request and you're not sure what to do. So what do you do? We're going to talk about what you're going to do after we talk a little bit about why this may have happened. So opioids and unrealistic expectations. Patients often have unrealistic expectations that could lead to the belief that opioids will always relieve their pain therefore more opioids are equal to more pain relief. This could lead to unsanctioned dose escalation or continued requests for higher doses and really this is an opportunity and a time for you to re-educate the patient about realistic goals for pain management and potential opioid risks. There are some different ways that you can monitor if your patient may have developed opioid misuse during the course of treatment. One questionnaire available is the current opioid misuse measure. It's self-administered, 17 items. It is, you know, the patient could falsely self-report so it is not, you know, not going to be completely foolproof. Other strategies you can use, pill counts, scheduled versus random as we talked about, urine drug testing and PDMP monitoring. Another important thing that you can do if you're concerned about misuse is get a history of reliable family members, wife, other loved ones who might be concerned about the patient. You should be aware that certain family members may have secondary gain issues and may give inaccurate information so it's important information to gather but may not always be reliable. These behaviors, though, have a differential diagnosis so there are three things that could be going on. You could have pain relief seeking, pain relief and drug seeking or you could have only drug seeking. So if you have pain relief seeking, are we seeing just disease progression, poorly responsive pain or basically therapeutic failure, withdrawal mediated pain, opioid analgesic tolerance, opioid induced hyperalgesia. The pure drug seeking would be, you know, we're maybe detecting an opioid use disorder, other psychiatric diagnosis or potentially criminal intent or diversion. However, most times it's actually more of a combination of the two. You can have a patient with chronic pain with comorbid addiction potentially who's taking the medication some for pain or potentially diverting some. So there is a differential here and we need to kind of get to the bottom of what might be happening. This can be a complex task and we do talk about this in some of the other lectures. We're going to talk about it a little bit here. So if it's pain relief seeking, basically the patient is no longer getting really good tolerance, excuse me, really good therapeutic benefit from the opioid, this could mean that there's been a right shift of the dose response curve so, you know, that over time we know that analgesic tolerance can occur and it has been demonstrated in animal models. Human studies do tend to find that opioid doses stabilize long term so, you know, we assume opioid analgesic tolerance is not common but it may happen. So it could happen in a patient. I think it probably happens less than we have been touting that it happens but it can happen and the way to overcome this is to increase the dose, however, we, dose of opioid, however we now know that just doing that for years and years can get us into a pretty dangerous situation. So this may not always be the right response. On the other hand, we could actually be seeing a harm of opioids where we're seeing opioid anesthesia so that we're seeing enhanced pain sensitivity to the same opioid dose over time and paradoxically more opioid in this situation would actually worsen pain and how this happens is basically central and peripheral sensitization that occurs that is pro-nocioceptive in its mechanism and so your increased dose of opioids may only improve analgesia for a short period of time and ultimately may actually worsen it. On the other hand, if we're seeing drug seeking behavior, so we're actually seeing some of the manifestations of opioid use disorder or addiction, some of the things that we would see would be potentially using the medication in larger amounts of duration than intended, a persistent desire to cut down and being unable to, giving up other interests in order to use opioids, spending a great deal of time obtaining opioids or recovering from them, leaving them, no longer fulfilling major role obligations, using in hazardous situations, continued use despite social or interpersonal problems, and continued use despite physical or psychological problems. So this is also known as the DSM-5 criteria for opioid use disorder and these are some of the things you might see. It is important to note that the tolerance and withdrawal, we actually do not count as criterion for opioid use disorder in a patient prescribed opioids because these occur with prescription use over time, so we actually do not count those, but if we're seeing the other behaviors or consequences listed here, then we would count those and that would potentially indicate that the patient has developed an opioid use disorder. In clinical practice, the clinical syndrome that you might see, if you can't remember that DSM-5, which is a lot of different factors to remember, is think of the three Cs, so is there loss of control, compulsive use, continued use despite harm, these are some of the behaviors that you might see. Your pattern and severity may indicate that an opioid use disorder has developed, but really it's important to remember that developing these symptoms is not the same as developing opioid withdrawal or having physical dependence, so that is a different process that's going on and is a consequence of just prescribed use of opioids over time. Some of the concerning behavior for opioid use disorder that you would see, sort of from the spectrum of yellow to red flags, a yellow flag would be requests for increased opioid dose, requests for a specific opioid by name, these are sort of soft signs, if you will, of maybe developing a disorder, which are going to be lesser than non-adherence with monitoring, lost or stolen prescription, or other illegal activities that you might see. So here's some of the spectrum that you may see, kind of listed from lesser to more concerning. Going back to that case, again, a patient on very high dose opioids, depression, high risk, asking for early refill, how are you going to manage it? He's asking to go out of town, he's asking for that prescription 11 days earlier. This is a patient that you actually want to see at an office visit, and you want to see him pretty urgently. At that visit, I would recommend that you're performing a urine drug test, performing a fill count, and if possible, confirming his story with a family member. This might require getting a letter from a physician who's caring for his daughter in the hospital, if you're really concerned that he may not be truthful with you. And your goals of that visit and that monitoring is really to reestablish the goals and expectations of treatment, and reassess the risks and the benefits of the treatment. If the risks start to outweigh the benefits, then it may be that you need to have a conversation about discontinuing the medication. There are certain medications that you want to avoid with opioids, so we're going to talk about that risk mitigation strategy. The high risk medications to avoid if your patient is prescribed prescription opioids include alcohol. We do advise against any use of alcohol during the treatment. And the reason is that alcohol can actually cause rapid release of opioids, also called dose dumping, particularly with certain extended release or long-acting opioids. So this can be a real risk and something that you need to counsel patients about. Even periodic use of alcohol can lead to this risk. Benzodiazepines and other sedative hypnotics are definitely a risk when concomitantly prescribed with opioids. The concomitant prescription has the highest risk for unintentional overdose. There are definitely potentiating effects of sedation and respiratory depression when these medications are co-prescribed. Certain muscle relaxers such as carisoprodol can have the same risks as benzodiazepines and sedative hypnotics, mainly because this particular medication, the metabolite, is a sedative hypnotic and can have the same risks. Marijuana may have risks when used concomitantly with opioids. This is a moving target, but in general some of its sedating effects may impair function and driving and other important factors which could increase risk. Medications that interact with methadone are important to avoid and there's a huge list of medications that can interact with methadone if it's prescribed for chronic pain and this is an important list of medications I want to refer to. Many different medications can interact with the tramadol and tepentadol which are partial mu-SSRI or SNRI medications, so you'd want to be concerned about avoiding those medications because they can increase serotonin syndrome risk or seizure risk. Let's talk a minute about abuse deterrent formulations. What I mean by that is that there are newly being developed abuse deterrent opioid formulations that were approved by the FDA that are undergoing approval currently. These are designed to be tamper resistant or co-formulated with medications that reverse opiate effects or produce noxious side effects when tampered. These are some of the new formulations we're seeing. Their effectiveness for reducing misuse and improving clinical outcomes is really yet to be established. They may be helpful particularly if patients are crushing or injecting opioids and they may seek patients to prescribe other prescription or illicit opioids. Here are some of the ways that they're being developed and used, so either physical barriers, agonist, antagonist combinations, certain aversive components, produgs, different routes of administration, and reducing drug rewards, but currently there's no proven abuse deterrent resistant opioid formulation. Finally we're going to talk about naloxone co-prescription, which is an important thing to be able to talk to your patient about, and some of the risks of overdose. We're talking about unintentional opioid overdose. Some of the risk factors we know are the highest risk is really prior overdose, so if your patient's had an overdose in any one year, that predicts a six-fold increased likelihood of an overdose in the next year. Any history of opioid overdose predicts a four-fold increased risk of mortality, so very high risk of repeat overdose if you've had one in the past. Certainly like we were talking about, the concomitant use of other substances can lead to increased risk, sedatives, alcohol, cocaine, and if the patient has been abstinent from opioids for a period of time and then resumes opioid at the higher dose, that can lead to opioid overdose unintentionally. Ways that we can reduce opioid overdose risk in times that we need to think about it more clearly, consider it when high-dose opioids are prescribed. This would be doses over 50 milligrams of morphine equivalents. If the patient has a history of an opioid overdose, intentional or unintentional, if the patient's prescribed benzodiazepines or other sedative hypnotics, if the patient has opioid use disorder or there's heroin use, these are all times that we want to be particularly careful about talking to the patient about opioid overdose risk. What we're talking about is really educating the patient of how to potentially reverse an overdose. This is the concept of prescribing naloxone or Narcan for opioid overdose. The reason that we need to give it to lay people is that overdoses are usually witnessed. Death takes a while. People don't always routinely access emergency medical services. We know that naloxone is safe and effective. It may decrease the need for advanced respiratory support, which can lead to severe consequences potentially. It may also lead to possible behavior change. Narcan or naloxone is not a controlled substance. There's no different from prescribing other routine medications to your patients. Some states have added legal protections to protect bystanders if they're administering naloxone to someone they witness having an overdose. There can in some states be prescribing or dispensing based on standing orders or directly from pharmacies. We're trying to get this medication out to more patients to decrease risk of overdose. There's several different ways to prescribe naloxone. It comes in an injectable intranasal formulation. The injectable, you can prescribe the vials with syringes. There's a newer formulation of an auto-injector that's available. There are intranasal formulations that come in pre-filled syringes. There's some mucosal atomizer devices that are on the market now. They're all listed here, as you can see, with some of their different things to know about them. I know in my state, they are still somewhat cost prohibitive. Working with your pharmacies and other things to make them more accessible to patients can be quite helpful. When you're talking about opioid safety, we're talking about using this for people who are prescribed high-dose opioids or other high risks. You could suggest that you're really using it for anyone prescribed opioids. Patients who are prescribed opioids may not perceive their own overdose risk in a realistic way. We're helping them understand that being prescribed opioids is a risk of having an unintentional overdose. Really, focusing on opioid safety with language such as, opioids can sometimes slow or even stop your breathing, naloxone is an antidote to opioids to be used if there's a bad reaction where you can't wake up. Helping patients understand that naloxone is for opioid medications like an EpiPen is for someone with an allergy. This is a medication that we need to be able to utilize if you're harmed by one of the most serious harms of opioids. It's really about keeping you safe. There are different resources here for providers listed that you might check out to help your patients talk about overdose and also to give them some good information. In summary, what we were talking about today was risk assessment, mitigation, and management. What we were talking about was evaluating a patient's risk of opioid misuse should be done universally on all patients prescribed long-term opioids. The level and frequency of opioid monitoring depends on his or her initial risk evaluation. Opioid monitoring involves several steps and helps determine whether the benefits of ongoing treatment outweigh the risks. Urine drug testing is a key monitoring component and we talked about that in depth. Naloxone co-prescription should be considered in patients prescribed high-dose opioids. There is some additional information you might access through the ACP Caring for Patients with Chronic Pain, Treating with Opioids, Balancing the Benefits and Risks, and Continuing Opioids Lecture. Thank you for your attention. Our references are listed here. There are several as well as some information about the PCSSO Colleague Support Program and LISTSERV and some information about PCSSO. Please take care.

Opioid risk assessment

Opioid mitigation

Opioid management

Universal precautions

Monitoring strategies

Urine drug testing

Naloxone co-prescription

Prescription drug monitoring programs

Comprehensive pain assessment

Differential diagnosis