Hi. I'm Roger Chow. I'm at the Oregon Health and Science University. I'll be presenting this module on evidence for and management of opioids for chronic pain for the provider's clinical support system. This event is brought to you by the provider's clinical support system, Medications for Opioid Use Disorders. The content and discussions during this event are prohibited from promoting or selling products or services that serve professional or financial interests of any kind. The overarching goal of PCSS MOUD is to increase healthcare professionals' knowledge, skills, and confidence in providing evidence-based practices in the prevention, treatment, recovery, and harm reduction of opioid use disorder. This is a disclosure to learners. AAP is committed to presenting learners with unbiased, independent, objective, and evidence-based education in accordance with accreditation requirements and AAP policies, all relevant disclosures have been disclosed and reviewed, and there is no relevant financial relationships to disclose. At the conclusion of this activity, participants should be able to describe opioid pharmacology, review the evidence on the use of opioid therapy for chronic pain, assess the risks and benefits of long-term opioid therapy for chronic pain, as well as factors associated with prescription opioid overdose and opioid use disorder, and apply an evidence-based approach to start, continue, modify, and discontinue or taper opioid therapy. Let's start with a case. So bear this case in mind. We'll come back to this case later on in the presentation. You have a 53-year-old female who's transferring care to you because her PCP is leaving practice. This patient has shoulder and hip pain secondary to avascular necrosis, has had shoulder replacements, hip decompression, as well as hip replacement, also has diagnoses of fibromyalgia, nonradicular low back pain, and chronic headache. In addition, the patient has depression and fatigue, gastroparesis, and irritable bowel syndrome. The patient's medications include morphine, immediate release, 30 milligrams, 5 tabs every 8 hours, plus oxycodone, 5 milligrams, 8 tabs every 6 hours. This comes out to a morphine equivalent dose per day of 690 milligrams. The patient is also on modafinil, 20 milligrams daily. The patient reports pain that is 6 out of 10 on average with some day-to-day fluctuation. She can carry out activities of daily living, but with pain, limited ability to exercise, and reports no aberrant drug-taking behaviors. This slide helps us to think about opioid pharmacology. There's actually several ways to categorize opioids. So this slide illustrates one way, which is to group opioids as being natural, i.e. opiates, and semisynthetic opioids versus synthetic opioids. So you can see the synthetic opioids are methadine, meparidine, and fentanyl. The natural opioids include morphine and codeine, as well as their metabolites. This can be useful because the natural and semisynthetic opioids are on a different metabolic pathway than the synthetic opioids. So again, it's one way to think about or classify these medications. This slide shows another way to think about opioid types. So you can think about opioids as those that are full mu agonists. So these are, quote unquote, pure opioids. These include morphine, oxycodone, hydrocodone, hydromorphone, fentanyl, methadone, and oxymorphone. We also have partial mu agonists. The main example of this is buprenorphine. We have dual mechanism agents. So these include tramadol and tepentadol. These drugs have mu opioid receptor effects, but also have central acting effects. And then we have mixed agonist-antagonist. The main example is pentazosine, which is not used very commonly in clinical practice. Opioids also come in multiple formulations and routes. So all opioids can either be immediate release or extended release slash long acting, ER slash LA. We have transdermal opioids. The examples there are fentanyl and buprenorphine. And then we have sublingual opioids. This is buprenorphine, which in its sublingual form is used off-label for pain. This slide shows some background on opioids and pain. As all clinicians know, chronic non-cancer pain is highly prevalent and results in substantial burdens. Estimates of chronic non-cancer pain vary. However, some estimates are that up to one-third of adults in the United States report some chronic non-cancer pain. We know that opioids are very widely prescribed for pain and that this is a relatively recent change in practice. The use of opioids in the United States markedly increased from around 1990s to 2010. In 2005, about 4% to 5% of US adults, so around 1 out of 20 to 1 out of 25 persons, reported use of long-term opioid therapy. In 2016, the proportion of Medicaid enrollees with at least one opioid prescription for pain was 11.3%. This had come down by 2019 to 7.2%. In 2015 to 2016, 17.5% of adolescents and young adults reported using a prescription opioid in the past year. It's also important to understand that use of opioids is quite different in the United States than from other parts of the world. The United States is really an outlier. We account for about 5% of the world's population, but we consume about 30% of the world's opioids, including about 80% of the global use of oxycodone and 99% of hydrocodone. Opioids are different from other medications because there are important harms related to the substance use disorder potential as well as the overdose risk. We know that there's large practice variations in the use of long-term opioid therapy. It's also important to recognize that there are disparities in pain management related to race, ethnicity, and other social drivers, including disparities related to opioid use. This slide shows patterns or trends in prescription opioid overdose deaths. So from 1999 to 2022, you can see that the green line and the bars, the green line shows prescription opioids, not including synthetic opioids, and then the bars are the total, so both prescription opioids plus synthetic opioids in particular, illicit fentanyl and fentanyl-related analogs. You can see from 1999 to around 2010, there was a marked rise in national overdose deaths involving prescription opioids. So there's a steady increase. There was about a quadrupling of overdose deaths over that 11-year-or-so period. We did see a leveling off from around 2010 and a slight increase through around 2016 in terms of prescription opioid overdose deaths, but then we started to see a marked rise in the numbers of deaths related to synthetic opioids, so that's the yellow line. And again, this is primarily fentanyl, illicit fentanyl and fentanyl analogs. The number of overdose deaths kind of peaked in 2016 to 2017. Unfortunately, it rose again during the COVID epidemic, so you see that the numbers came down to 14,139 in 2018 and then bumped up again in 2021. I think the good news here is that there has been some progress at least related to prescription opioid overdose deaths, though as you can tell here that the major issue at this point is overdose deaths related to synthetic illicit fentanyl. This slide summarizes the evidence on the effectiveness of opioids versus placebo or no opioids, so this is based on a systematic review that we did that was funded by the Agency for Healthcare Research and Quality. We conducted meta-analyses of all the trials of opioids versus placebo or no opioids. There's a few important points to take from this slide. It's a busy slide, but I'll try to summarize the main conclusions. I think if you look at the interpretation column, you can see that for all of these outcomes, so pain intensity, pain response, function, SF36, and sleep quality, we either see small benefit or no benefit. So the benefits of opioids versus placebo are not large and probably smaller than most people perceive. If you look at pain intensity, so this is the average improvement in pain on a 0 to 10 point pain scale, we have over 70 trials with almost 21,000 patients. The main difference is less than one point on a 0 to 10 point pain scale. So this means that someone's pain instead of being say 7 or 6 out of 10 would be 6 or 5 out of 10 with an opioid versus placebo. Pain response is another way of looking at efficacy. So this is the likelihood of whether somebody will experience a greater than or equal to 30 percent improvement in pain. Again, we have a fairly large number of trials. Opioids are associated with an increased likelihood of experiencing a pain response, a relative risk of 1.33, which again is a relatively small benefit. The absolute risk difference is about 14 percent, which means that you have to treat approximately eight people with an opioid for one person to experience a greater than or equal to 30 percent improvement. For function, again, it's a minimal small benefit. That's a standardized mean difference. Minus 0.2 to minus 0.5 would be considered a relatively small difference. You can see looking at SF36 physical health status and mental health status, the difference is around less than 1 point to 1.65 points on a 0 to 100 scale. So essentially a trivial effect and then a small effect on sleep quality. So again, the benefits are not large with opioids for pain intensity, less than a point on a 0 to 10 point pain scale. On the other hand, if you look at short-term harms of opioid therapy, so these are all very well-known harms that people experience on opioids, things like nausea, vomiting, constipation, somnolence, dizziness, pruritus, you can see that opioids increase your likelihood of experiencing all of these side effects by two to threefold or slightly more than that. And you also see that opioids are associated with an increased likelihood of discontinuation due to adverse events, which we often interpret as a marker of intolerable or more severe adverse events. We also looked at opioids versus non-opioid pharmacological therapy. So this is comparing an opioid to, say, an NSAID, acetaminophen, or another drug like a tricyclic antidepressant. And I think this slide is—these results are often also surprising to people. We don't have as many studies, but the results are fairly consistent. Again, if you look at the interpretation column, it's either a minimal benefit or no benefit. So this is compared to a non-steroidal anti-inflammatory drug or another non-opioid pharmacological therapy. So the mean difference in pain is minus 0.18 points on a 0 to 10 point pain scale. This is a very small difference. Most people would consider this to be trivial. And you can see that there's essentially no effect in terms of pain response function and the other outcomes. So again, this seems often surprising to people that opioids are perceived as being much stronger analgesics. But when carefully studied in these randomized controlled trials, there's actually no difference between other therapies that we use for pain. In terms of longer-term effects of opioids, we actually have no placebo-controlled trials. We do have this space, randomized controlled trial of step therapy starting with an opioid versus initial non-opioid therapy for chronic low back pain and osteoarthritis pain. This is the only one-year RCT that we have. It was a one-year VA trial conducted in primary care with 240 patients. In this trial, all patients received individualized medication management using a collaborative telecare pain management model that's used in the VA. The average opioid dose was 26 morphine equivalent per day in the opioid arm versus 1 milligram, so very small amounts in the non-opioid initiation arm. At 12 months, this trial found no difference in function and pain was actually slightly worse in the opioid group. So again, perhaps surprising findings to many. As expected, the opioids were associated with more adverse events. There were no deaths or cases of opioid use disorder in this trial, but the trial was really not designed to look at those types of serious outcomes. This slide illustrates the results for pain intensity in the space trial. So you can see at the start of the study, the mean EPI, that's a brief pain index severity, was equivalent in the opioid and non-opioid groups. But at 12 months, it's actually slightly higher in the opioid group at 4.0 versus 3.5 in the non-opioid group. This is on a 0 to 10 pain scale. So again, the pain was slightly higher in the opioid arm than in the non-opioid arm. As I mentioned, the randomized controlled trials have not been designed to look at opioid use disorder and other serious outcomes. These can be difficult to study, and the studies usually actually try to exclude patients who may be at increased risk of these types of outcomes. So you have to look at observational studies. And in observational studies, the rates of misuse average between 21 to 29 percent in people using opioids, rates of opioid use disorder, so DSM-5, DSM-5 criteria average between 8 percent to 12 percent. It is important to recognize that the definitions for misuse and opioid use disorder were inconsistent across studies, and the methods to detect these outcomes have not been well standardized. If you look at studies that use much more, you know, rigorous methods, we do find higher rates of some of these outcomes. So one study in particular that was based on detailed standardized interviews with over 800 patients found that 26 percent reported purposeful over-sedation, 39 percent reported increasing their dose without a prescription, 8 percent reported obtaining extra opioids from other doctors, 18 percent reported using opioids for purposes other than pain, and 12 percent reported that they hoarded their pain medications. So all of these would be considered misuse behaviors and with important safety concerns, and again, indicate some of the potential harms related to opioids. There are a number of risk factors for opioid overdose. One is having a history of misuse behaviors, so these are some of the things we just talked about in the prior slide, so this includes obtaining prescriptions from multiple providers, running out of opioids early, losing your prescription, unauthorized dose escalations. The period right after starting opioids is a higher risk period. Methadone is associated with increased risk of overdose. This has to do with the pharmacology of methadone, which is trickier, as well as some other pharmacological aspects of that medication. Concomitant use of benzodiazepines and some other drugs is also associated with increased risk of opioid overdose. Substance use, so other substances being used along with opioids. Presence of psychological comorbidities, such as depression, anxiety, PTSD, and being on higher doses of opioids. So all of these things can be useful for identifying people who may be at higher risk for serious adverse events related to opioids. A number of studies have looked at the association between higher opioid dose and overdose risk. In these studies, we've consistently seen that higher doses are associated with an increasing overdose risk, and this is after adjusting for potential confounders, such as other comorbid conditions, use of other medications, et cetera. So for example, in this first study, which was a cohort study, you can see that the risk of opioid overdose in people taking over 100 milligram morphine equivalents per day was 8.9. This is compared to people on less than 20 milligrams per day. And it even increased when you were at 20 to less than 50 milligrams per day with a hazard ratio of 1.4. You can see a similar pattern in the case control study conducted in the VA. In the third study, which was a nested case control study conducted on Ontario, the hazard ratios were not quite as high with the higher dose, but you still see a doubling of risk when you get to 100 milligrams per day. So we're going to run through the evidence-based guidance and recommendations for opioids. This first slide addresses initiation and titration of opioids. Given what we've just discussed, namely that the benefits of opioids are relatively small, they do not seem to be superior to other non-opioid medications in terms of analgesia function and other outcomes. They are associated with short-term adverse events as well as an increased risk of overdose and opioid use disorder. Given all this, opioids are not or should not be considered first-line therapy for chronic pain. In appropriately selected patients who do not respond to non-opioid therapy, opioids may be considered. However, the initial course of opioids should be viewed as a short-term therapeutic trial with patients reassessed within 1 to 4 weeks. With opioids, it's important to always start low and go slow. As we just discussed, higher doses are associated with increased risk of overdose, and because it takes time to develop tolerance, increasing the dose too rapidly will increase risk of overdose. Immediate release opioids are recommended for initial therapy. This is because the benefits of long-acting, round-the-clock opioids are unclear, and you also have to be cautious about using long-acting opioids in people who are opioid naive, who do not yet have physical tolerance. There are potential harms with using long-acting, round-the-clock opioids related to induction of tolerance as well as increased endocrinologic side effects. Long-acting opioids may be used to help stabilize therapy in people who use frequent immediate release opioids once they've, you know, been on the therapy for, you know, a period of time. Methadone and fentanyl are not recommended for initiation or as first-line options for long-term opioid therapy because of more complicated dosing and pharmacokinetics as well as overdose risk. And buprenorphine, which as we discussed earlier, is a partial agonist, may be an option for chronic pain in higher-risk patients. The evidence shown that buprenorphine is safer is lacking, but there is theoretical reasons to think that buprenorphine might be safer in terms of overdose risk, and this is because the respiratory depressant effects plateau with buprenorphine. And so this is unlike other drugs, other opioids, excuse me, where with higher doses the respiratory depressant effects continue to go up. It's important to recognize that higher-dose buprenorphine formulations are only approved for treatment of opioid use disorder. So if you're using them for a pain that's an off-label use, the transdermal preparations formulations, I should say, of buprenorphine approved for pain are lower-dose formulations. This slide provides information about initiation of opioids, focusing on immediate release formulations. So we will go into this slide in detail. This is mostly for reference, but it provides a typical starting dose for the various immediate release opioids, and then some considerations to think about, including whether the opioid is a, you know, high, moderate, or low-potency opioid. This slide is analogous to the prior slide, but focuses on extended release and long-acting formulations. On this slide, some of the ERLA formulations are transdermal. So again, low-potency buprenorphine, as well as fentanyl, which is a high-potency opioid. Those both come as transdermal preparations. In particular, the fentanyl should only be used in opioid-tolerant patients already on higher doses of opioids. And then there's other considerations related to specific opioids to consider, again, including whether it's a low, moderate, or high-potency medication with tepentadol and tramadol, avoiding concomitant seroconin products because of the central acting effects of those drugs. The next slide will address methadone in a little bit more detail. This slide addresses initiation of methadone. As mentioned before, methadone is not recommended as to be used for initiation. Methadone has more complicated pharmacokinetics and other properties. We recommend caution with this drug because of inter-individual variability in the pharmacokinetics, a prolonged half-life, potential arrhythmogenic effects, as well as incomplete cross-tolerance with other opioids. Again, it's not considered first-line for management of chronic pain. Other opioids are preferred because of less complicated pharmacokinetics and a better safety profile. If you do use methadone, we recommend doing a baseline ECG because of the QTC prolongation risk and not using methadone in people who have QTC prolongation to start with. Methadone should always be started at a low dose. For opioid-naive patients, it should be initiated at 2.5 milligrams three times a day. We'll talk about how to rotate patients from another opioid to methadone on the next slide. And again, the recommendation is to do a slow dose increases, no more than 5 milligrams per day every 5 to 7 days, and this is related to the very long half-life of methadone compared to other opioids. This slide addresses dosing considerations. So with most opioids, there's no theoretical ceiling. So this is unlike, you know, almost any other drug that we prescribe where there's a, you know, recognized or recommended maximum dose. But even though there's no theoretical ceiling with opioids, there is little evidence to guide prescribing at higher doses. There are additional risks, including hyperanalgesia, endocrinologic risks, unclear benefits of higher doses, and using higher doses may be a marker for opioid use disorder or other issues. As previously discussed, higher doses of opioids are associated with increased risk of overdose. Definitions of higher dose have varied over the last, say, 10 years or so and continue to evolve. The trend has been towards lower dose thresholds based on new evidence on dose-dependent overdose risks. Several guidelines have addressed opioid dosing In the 2009 American Pain Society American Academy of Pain Medicine guideline, greater than 200 morphine milligram equivalents per day was defined as higher dose. The 2016 CDC guideline recommended caution at 50 to 90 milligram morphine equivalents per day and to avoid over 90 per day. And the most recent 2022 CDC guideline did not define specific death dose thresholds but recommended using the lowest effective dosage. In some patients who, you know, may experience some benefits from higher dose, it's still important to mitigate risks of using the higher dose. Our patients should be counseled on the risks of using higher doses and provided an opportunity to taper if they wish to do so. They do require more frequent or intense monitoring. If patients are not achieving their therapeutic goal, you should consider tapering them down or off of the opioid. Naloxone, which is an opioid antagonist is recommended to be provided in conjunction with overdose education, but naloxone can be given by a family member or other person if the patient has a witnessed overdose. And you should always avoid co-prescribing other benzodiazepines and other medications that may increase overdose risk. This slide provides a table for toculating morphine equivalent doses. It's not meant to be used for opioid rotation. It's just meant to be used to calculate morphine equivalent doses so you can understand the relative dose that somebody is on with their opioid. So you can see the conversion factors which range from quite small for coding, so that's a low potency opioid, 0.15. One milligram of coding is equivalent to 0.15 milligrams of morphine, whereas for a medication like hydromorphone, one milligram of hydromorphone is equivalent to four milligrams of morphine. You can see with methadone, the conversion factor is thought to vary at different doses and it goes up in people at higher methadone doses. There are a number of strategies that can be used to mitigate risk associated with opioids. One is appropriate patient selection. So again, recognizing people who are at higher risk related to their substance use disease history, psychiatric comorbidities, use of other medications, et cetera. And in those patients, opioids should be avoided or be used very cautiously. Avoiding higher doses, you know, only using the doses that are necessary. Conducting monitoring, including urine drug testing. Reviewing prescription drug monitoring data. So this is to see if patients are obtaining scheduled substances from other facilities or providers that may increase their risk. Avoiding sedative hypnotics, in particular benzodiazepines. Performing more frequent follow-up based on the level of assessed risk. Obtaining addiction, pain, or psychiatric consultation if necessary. Doing more frequent refills with smaller quantities. And again, naloxone co-prescription to reverse opioid overdose if that occurs. A little more about urine drug tests. These are recommended to help identify risky behaviors that would otherwise be undisclosed. Urine drug tests are non-invasive. They provide some objective documentation of, you know, how the medications are being taken, including the use or absence of prescribed drugs, use or absence of non-prescribed drugs, as well as illicit substances. And urine typically has a longer window of detection compared to blood. So it's useful from that aspect. In terms of when to perform urine drug testing, it should be done at baseline in periodic rule. The interval may be guided in part by the assessed level of risk. Urine drug testing should generally be performed if aberrant behaviors are suspected and if there have been major changes in treatment. One to two times per year may be appropriate for low-risk patients, three to four or more times per year may be appropriate for higher-risk patients. It's important to recognize that doing individualized or random testing may miss some abnormal tests that may also provide higher yield and reduce costs compared to testing everybody all the time, and that patients may have some opportunities to tamper or alter their behavior if they know that there's going to be testing performed. So urine drug tests are certainly not infallible, but they do provide an additional data point, and again, all with an eye towards patient safety. Opioid switching or rotation is an issue that can come up. This is defined as switching from one opioid to another to improve therapeutic outcome and or to avoid adverse events due to the current drug. So if somebody taking a certain opioid is having a lot of side effects, say constipation, you may consider switching them to another opioid, also if they aren't experiencing, you know, pain relief or efficacy. The theory behind opioid switching or rotation is that there is some variation in activity at new receptors, so this can lead to some improved benefit versus development of AE when you switch from one to another. Some other considerations are, you know, are patient wishes, how adherent they are to therapy. There may be cost or insurance concerns with, you know, the particular opioid that's being used or that you're considering switching to. The importance of titrating, which can lead to adverse events and also poor analgesia, and then recognizing potential drug-drug interactions. Opioid switching or rotation can be tricky. It's important to seek expert advice. If you are not experienced in switching opioids and patients prescribe long-term opioid therapy, as previously discussed, you can calculate the current morphine equivalents per day using an opioid conversion calculator, but you should not, you know, directly convert somebody to the same morphine equivalent dose, and again, this is related to incomplete cross-tolerance. For all opioids other than fentanyl or methadone, we apply an automatic dose reduction window of 25 to 50% lower than the calculated equal analgesic dose. The previous opioid should be stopped when you're starting the new opioid. It's important not to overlap doses and to reassess patients frequently. Fentanyl and methadone are more tricky, and there are, and I will address those in a bit here. Rotating to methadone. As discussed before, methadone can be quite a bit trickier. It's thought that there's much less cross-tolerance to methadone when you're on another opioid. So people, even though somebody may be tolerant to, you know, a high dose of another opioid, they may have very little tolerance if you switch them to a similar or even reduced dose of another opioid. So in patients who are currently on another opioid at less than 40 to 60 milligram morphine equivalents per day, it's recommended to start the methadone at a very small dose, 2.5 milligrams, three times a day. This is basically as if they're opioid naive on the same recommendations about increasing the dose no more than 5 milligrams per day every 5 to 7 days. In patients who are on over 60 milligram morphine equivalents per day, it's recommended to start the methadone at a dose 75 to 90% less than the calculated equi-analgesic dose, but no higher than 30 to 40 milligrams per day. And to not increase the dose any more than 5 to 10 milligrams every 5 to 7 days. And again, the doses that you switch the methadone to are much lower than the calculated morphine equivalent doses due to incomplete cross-tolerance and the long half-life. So this slide addresses rotating to the fentanyl patch, which is also more complicated than for other drugs. You start by calculating the 24-hour opioid analgesic requirement, converting that to the equal analgesic oral morphine dose, and then using the table you can determine the initial fentanyl transdermal dose. Again, the previous opioid should be stopped when you initiate the fentanyl patch, and you can start titrating the dose three days after the initial dose, and then six days after subsequent doses, and don't titrate more frequently than that. Because the initial dose may be low, it's important to reassess patients frequently after you make the switch. Patients should be tapered or weaned off of long-term opioid therapy when they engage in intractable aberrant drug-related behaviors or drug misuse slash diversion. Patients with opioid use disorder should be offered treatment or referred for treatment for this condition. Patients should also be tapered or weaned if they experience no progress towards meeting their therapeutic goals or they experience intolerable adverse effects. It's important to remember that you need to continue to manage the pain and the patient using non-opioid therapies. You're stopping opioid therapy, you're not abandoning the patients. It's important to have an exit strategy when initiating a trial of long-term opioid therapy. This means knowing what your indications will be for stopping opioid therapy, having plans for tapering or discontinuing the opioid, providing psychosocial support, and knowing your resources for managing addiction and mental health issues. There's no longer required to have a waiver, a DEA waiver for office-based management of opioid use disorder with buprenorphine. Though it's still important to understand how to use buprenorphine for management of opioid use disorder and we encourage people to do the training. One important point is that tapers need to be very slow. We found that patients, if you try to do a fast taper, i.e. over weeks to one or two months, that can be very difficult. Patients can experience a lot of withdrawal and have a lot of difficulty tapering. And we found in practice that slow tapers over months or years are often required. In terms of thinking about the decision about whether to continue or discontinue opioids, it's useful to think about this in terms of a risk-benefit framework. The main benefits are related to improvement in pain, function, and quality of life. And then the risks and harms are related to misuse, opioid use disorder, and overdose, as well as adverse effects. There can be a number of pitfalls and, you know, stress making these decisions. Patients may really feel that they need the opioids, that you don't trust them. If you think that it's, you know, in their best interest to stop the drugs, or they may say that they will engage in other, you know, harmful behaviors. A useful response is, I cannot continue to prescribe a medication that is not helping you or is hurting you or both. And again, you're not abandoning the patient. You're stopping the opioid therapy and you're using other non-opioid pharmacological therapy as well as non-pharmacological therapies to manage the pain. This slide provides a framework in terms of how to approach an opioid taper or cessation. There are different indications for doing a taper or cessation. So these include having a, you know, diagnosing their patients with substance use disorder, which warrants immediate referral and initiation of treatment for opioid use disorder with pharmacological therapy, providing a naloxone rescue kit. In some cases, this may mean inpatient management but can also be done outpatient with buprenorphine or methadone. In somebody at high risk for immediate serious harms, the taper should be done within weeks to months. So a faster taper, providing supportive care, again, with naloxone can often be done outpatient. In patients who are at lower risk or their indication for doing a taper is therapeutic failure, typically the taper can be slower, i.e. months or months to years. Again, they should receive supportive care as well as a naloxone rescue kit. This can usually be done as an outpatient and buprenorphine is often an appropriate option. Diversion is a separate category. So these are patients who are not actually taking their opioid but are selling or, you know, otherwise, you know, giving an opioid to somebody else. So they do not have physical dependence. So no taper is required in this patient. And then the intervention will be based on the specific circumstances of that patient. This slide provides details about medications to help manage opioid withdrawal symptoms. So this is for people who are undergoing a taper or in whom their opioid is being discontinued. So for sweating, anxiety, or agitation, clonidine can be used. For anxiety, we can use hydroxyzine. For nausea and vomiting, Phenergan or Zofran are useful anti-emetics. For abominable crapping and diarrhea, hyacinamine can be used. And then for managing the pain, ibuprofen and pylenol. There are some geriatric considerations for a number of these drugs, including, you know, related to the sedative effects, risk of falls, anticholinergic effects, et cetera. So those are listed in one of the columns here as well. So in conclusion, what is the evidence on opioids? As we've seen, opioids are associated with modest short-term benefits versus placebo for chronic pain. Increased risk of various opioid-related side effects. Opioids have similar effects versus various non-opioid pharmacological therapies for chronic pain. The evidence on long-term benefits is limited, but indicates no clear benefit versus non-opioid therapy. Evidence also indicates potential serious harms of long-term opioid therapy, including opioid use disorder and overdose that appear to be dose-dependent. Taking all this evidence together, the evidence suggests, at best, a close balance of benefit to harm. Therefore, for chronic pain, our opioid should be reserved for appropriately selected patients with persistent pain despite non-opioid therapies. If long-term opioid therapy is prescribed, it's critical to monitor patients and utilize risk mitigation strategies. Patients on high doses warrant reevaluation, additional monitoring, and follow-up. And doses, opioid doses should be decreased or discontinued in patients who are not improving or in whom benefits do not outweigh harms. So, going back to our patient, recall this patient did not appear to be clearing benefiting despite using very high doses of long-term opioid therapy. She also had significant GI symptoms, which were likely exacerbated by the opioids. The patient was not exhibiting signs of aberrant behaviors, but did have a history of psychological issues as well as other comorbid pain conditions. In this patient, a slow taper was initiating over around two years. The morphine dose, which started at 450 milligrams per day, was reduced to 120 milligrams per day over that time. So, a slow taper over, you know, two years. The oxycodone dose was decreased from 160 milligrams per day to 5 milligrams twice a day. So, this means that the patient went from 690 milligrams morphine equivalents per day to 135 milligrams per day. So, a substantial reduction. We added non-opioid medications, duloxetine and SNRI with analgesic effects, 30 milligrams per day, and buspirone, which is an anxiolytic that is not sedating like benzodiazepines and is not associated with increased overdose risk at 30 milligrams twice a day. In this patient, the pain and function were no worse with the taper than when she was on the high doses. She did not experience serious withdrawal. There were some periods of acute pain, and we did temporarily increase the opioids to help manage those periods, and the eventual goal is to titrate down to less than 100 milligram morphine equivalents per day. This slide summarizes the evidence-informed approach to appropriate use of opioids. The preference is to use non-opioid therapies, recognize that not all patients are appropriate for opioid therapy, use risk assessment to inform decisions, including patients who may not be appropriate for opioid therapy, initiate opioids at low doses and titrate slowly, review initial treatment with opioids as a therapeutic trial, perform routine monitoring and risk mitigation. Opioids should be titrated based on the responsiveness of patients to initial low doses. It's critical to taper patients who aren't responding or who are experiencing adverse effects that outweigh the benefits. Be very cautious about utilizing higher doses. There appear to be little incremental benefit with dose escalation, but increased harms, including serious harms like overdose. Slide 38 shows references. These are continued on slide 39. This slide describes the PCSS MLUD mentoring program, which is provided as a service for clinicians who are interested in receiving mentoring related to management of addiction, pain and evidence-based treatment for these conditions. It's a no-cost program. There is also a PCSS MLUD discussion forum where clinical questions can be posed to colleagues to help you if you're encountering something in your practice. PCSS MLUD is a collaborative effort led by the American Academy of Addiction Psychiatry in partnership with many organizations. These are listed on this slide, as well as the following slide. And I think this ends this presentation. Thank you for joining.

opioid management

chronic pain

opioid use disorder

opioid pharmacology

opioid therapy risks

non-opioid therapies

patient monitoring

opioid tapering