Hi, welcome to this module, which is called an overview on the use of opioids for low back pain. I'm Roger chow I'm at Oregon Health and Science University, and I'll be presenting this module. In terms of disclosures, I have no relevant financial relationships with ineligible companies. The content of this activity may include discussion of off label or investigative drug uses. And I'm aware of the need to disclose this information. The overarching goal of is to train healthcare professionals and evidence based practices for the prevention and treatment of opioid use disorders, particularly in prescribing medications, as well as for the prevention and treatment of substance use disorders. In terms of the educational objectives. At the conclusion of today's module participants should be able to evaluate the benefits and harms of opioids in patients with low back pain. Analyze an evidence based approach to the selection of patients for opioid therapy for low back pain. Integrate an evidence based approach to the management of opioids for low back pain and apply strategies for mitigating risks associated with opioids. This slide shows an overview of the content of the module. We'll start with the case of a patient presenting with low back pain. We'll review the epidemiology of low back pain and opioids, present evidence on benefits and harms of opioids, discuss guidelines on opioids and low back pain, review risk assessment for use of opioids. Also, look at dosing strategies and risk mitigation, and then go back to the case to put it all together. So here's the case. Mr. S is a 57 year old with low back pain for two years, no specific inciting event. He has no associated leg pain or other neurological symptoms. His pain has been slowly worsening to the point of not being able to walk more than two to three blocks. He rates the pain as seven out of 10 on most days. He continues to golf most weekends but used to walk. Now he's riding a cart. He works as an engineer. X-rays show lumbar disc degeneration and facet joint arthropathy. He has tried acetaminophen and NSAIDs and has undergone PT. And he asks, what do you think about trying an opioid? So some background. Low back pain is the third most common reason for U.S. office visits. The lifetime prevalence for any low back pain episode is up to 84%, with a point prevalence of 7.5%. Low back pain accounts for over 16 million low back pain office visits per year, and 5% of PCP visits are for low back pain. Low back pain and neck pain together accounted for the highest direct health care costs in 2016 among all studied conditions. This was over $134 billion. And pharmacy costs account for about 20% of the total health care expenditures for low back pain. In addition to the direct costs related to treatments and management of low back pain, there are actually also very high indirect costs. Low back pain is the most common cause of activity limitations in persons under the age of 45. It's a common reason why people are unable to work or unable to fully work. This slide shows trends in the patterns of the prevalence of chronic low back pain. And what it shows is that we've actually experienced an increase in the proportion of people who have low back pain. So this was a study conducted in North Carolina. The same survey was done in 1992 and then repeated in 2006. You can see that among all people, the overall population, about 4% reported chronic low back pain in 1992, and this has more than doubled to 10% in 2006. And similar trends have been seen when you stratify people by age group in every age group. Other data also indicate that prevalence of chronic low back pain is rising. A study conducted in the VA showed that the prevalence of low back pain rose 4.1% per year from 2004 to 2011. So this is concerning because it indicates that despite what we're trying to do to manage this condition, that people seem to be impacted more by it. This slide reviews opioid prescribing patterns. In parallel with increased prevalence of low back pain, we're also seeing increased use of opioids in patients with low back pain. Prescribing rates more than doubled, with a 108% increase from 1997 through 2004. This correlates with an over 400% inflation adjusted increase in expenditures. Over 50% of regular prescription opioid users have low back pain, so low back pain is the most common reason why people use regular prescription opioids. There is some, I think, better news, which is that more recently some data indicated decrease in opioid prescribing for new low back pain, dropping from 28.5% in 2011 to 20.4% in 2016. A high proportion of patients with low back pain are prescribed opioids, and in some studies opioids are the most common prescription medication for low back pain. Which patients with low back pain are treated with opioids? We actually see that there's variations in use of opioids among people with low back pain, and you can't explain the variations by differences in pain severity. Some things that appear to be associated with increased likelihood of opioid prescribing include presence of greater psychological distress, having a poor health and unhealthy lifestyles, use of sedative hypnotics like benzodiazepines, and similar factors are associated with use of high dose opioids, as well as just with opioids use. Data indicate that use of opioids related to the presence of psychosocial factors that can put patients at increased use for adverse opioid related drug events. This is what we call adverse selection, meaning that people who are at higher risk are the ones that actually tend to be the ones that are prescribed more. So let's review the evidence on opioid therapy, starting with benefits. So, evidence indicates that the benefits of opioids for chronic musculoskeletal pain are quite small. Randomized trials have found opioids associated with modest short term effects on pain and function versus placebo, by short term I mean less than six months. This is from a meta analysis that we conducted. This was a review that was funded by the Agency for Healthcare Research and Quality. We did a meta analysis where we pooled 50 randomized trials reporting pain with almost 17,000 patients. The mean difference was minus 0.67 on a zero to 10 scale so less than one point on a zero to 10 scale versus placebo. The 95% confidence interval range from minus 0.81 to minus 0.54. For function, the meta analysis included 34 randomized controlled trials with over 11,000 patients. There was a standardized mean difference of minus 0.21. This is considered to be a small effect. Until recently we had no studies on long term defined as over 12 months outcomes of opioid therapy versus non opioids. And until recently we had no placebo controlled trials of opioids for acute low back pain. However, some opioids do appear to be similar and effective to NSAIDs for low back pain so no more effective than NSAIDs. And the recently completed OPAL trial, which was just published before we're presenting this module, actually showed that opioids were not associated with beneficial effects in patients with acute low back pain. That's the first placebo controlled trial of opioids for acute low back pain. The SPACE trial is an important study. This was the first longer term randomized controlled trial of opioids for chronic low back pain. This was not a placebo controlled trial. What this study did was it compared steps therapy starting with opioids versus steps therapy starting with non opioids for people with chronic low back pain and osteoarthritis pain. This was published in 2017. It's a one year VA trial conducted in a primary care setting. There were 240 participants. The trial was open label for patients and clinicians, meaning they knew if the patient was getting an opioid or a different medication. Assessment was mass so people who are assessing outcomes like pain and function did not know what medications the patient had received. Within the VA model, all patients received individualized medication management with a step pair approach within a collaborative telecare pain management model. In terms of the findings, opioids were associated with increased risk of more adverse symptoms, and the study was not designed to assess serious harms. There were no deaths or opioid use disorder cases that occurred. This just shows the drugs that were used in the space trial in each of the arms. So you can see in the opioid therapy arm. Step one, which is what people started with included immediate release morphine, oxycodone, or the combination of hydrocodone and acetaminophen, whereas in the non opioid arm patients started with acetaminophen or NSAID and no opioid. Step two, patients in the opioid therapy arm could be stepped up to sustain release morphine or oxycodone, whereas in the non opioid therapy arm, they were given adjuvant oral medications, nortriptyline, amitriptyline, gabapentin, and topical analgesics. And then you can further step up after that. Some patients in the non opioid therapy arm did receive opioid medications, but you can see there was quite a difference in terms of the milligram morphine equivalence at 12 months, which was 21 milligrams on average in the opioid therapy arm versus one milligram in the non opioid therapy arm. In terms of the baseline severity, you know, this is the excuse me, this is the outcomes at 12 months. So you can see for the BPI, which is the pain index, which is scaled and scored on a zero to 10 scale at 12 months, it's actually slightly higher in the opioid therapy arm than in the non opioid therapy arm by about one half point. And that was a statistically significant difference in terms of the proportion of patients who had their pain severity significantly improved. It was slightly less in the opioid therapy arm than in the non opioid therapy arm. And then in terms of the intensity significantly improved, it was about equivalent, 59% versus 61%. The interference scale measures function, like how much pain is impacting function, also scored to 10 scale. And at 12 months, there was no statistically significant differences between groups with essentially identical BPI interference scores. So you can see there's no difference in pain interference, and in terms of pain severity, opioids perform slightly worse than on opioid therapy. So this illustrates graphically the results for pain intensity. This is for mean BPI severity. So you can see on the left side patients start with the same baseline pain. On the right baseline are people who randomized to opioids and they end up at a four, and the non opioid arm are people who are randomized to the non opioid step therapy arm, and they end up at 3.5 or slightly better. And for pain interference with function, you can see that the final scores are essentially identical between groups. The unique characteristics of opioids, and that can make challenging to use in practice is that it has misuse potential related to its addiction potential. In primary care settings, the rates of misuse with opioids average between 21 to 29%. The rates of addiction or use disorder average between 8 to 12%. It's important to recognize that definitions for misuse addiction and similar terms are inconsistent. Many studies do use outdated or potentially stigmatizing terminology which we are trying to move away from, and understand that the methods used to detect misuse are poorly standardized, which can lead to some of the variability we've seen in estimates. One study, a large study with over 800 patients that conducted standardized two hour interviews of patients on chronic opioids reported high rates of concerning behavior. So this is doing detailed, you know, in depth interviews with patients. 18% of patients in this study reported purposeful over sedation with opioids or taking opioids on purpose to make them sleepy or to help them sleep. 8% reported increasing their dose without a prescription. 8% reported obtaining extra opioids from other prescribers. 18% used for purposes other than pain. So for example, treating depression or anxiety, and 12% reported their pain medication so kept an extra supply. All of these behaviors are concerning in terms of, you know, safety considerations. And as mentioned, these rates are relatively high. And, you know, without doing these detailed interviews might be hard to pick up. Prescription drug overdose prescription drug overdoses are an important concern with opioids. We saw large increases in prescription opioid overdoses nationally from around 1999 to 2010. These rates subsequently stabilized. Overdose trends have paralleled opioid prescribing trends. We have about 15,000 cases per year that's gone up slightly since COVID. In some states opioid related overdose deaths exceed motor vehicle accidents as the most common cause of accidental death. Motor vehicle accidents were previously the most common cause of accidental death in young and middle aged adults. Opioid overdose deaths exceed deaths from heroin and cocaine combined. And more recently, we've seen large increases in opioid overdoses related to heroin, then illicit fentanyl and analogs, which have created many serious issues in the last five years or so. This slide shows what happened around 1999 to 2010 when we saw a very large increase in sales of opioids, so about a fourfold increase of sales, which paralleled a fourfold or so increase in deaths, and then increasing treatment admissions for opioid use disorder. And as mentioned, since 2008, we've seen more than 15,000 deaths per year, exceeding MVA deaths in most states. This slide shows some patterns that extend out more recently. So you can see the yellow line. So I'll start with the orange line. The orange line is prescription opioids. So you can see from 1999 to around 2010, there's a steady increase in overdose deaths involving prescription opioids. The yellow line is heroin, and you can see that until around 2010, those rates are pretty low compared to prescription opioids and fairly steady. But around 2010, we see an increase in heroin-related deaths. And then, as I mentioned, the most concerning trend in the last five to eight years is the light blue line, which is synthetic opioids, which, again, were very low prior to around 2013 and started to go up in 2014 and sharply rise around 2015. And so these account for a large proportion of drug-involved overdose deaths because synthetic fentanyl is very potent, it's very cheap, and people often will get it in their drugs without realizing it, and it can cause overdose-related deaths. Some of the risk factors for overdose include being on higher-dose opioid therapy, concomitant use of CNS depressants, in particular benzodiazepines, recent initiation of opioids, so the period right when you start opioids. If you haven't been on opioids before, you don't have tolerance, that's a high-risk period. Presence of psychological comorbidities, aberrant drug-related behavior, so many of the things that we discussed on the prior slide, like taking opioids for things other than treating pain, increasing doses on your own, getting opioids from multiple providers. Methadone is a risk factor. We'll talk about that a little bit more, but methadone has some unique properties that makes it more challenging to treat and potentially increases its risks. Certain medical comorbidities, such as sleep apnea, can increase risk for overdose and then having an active or prior history of substance use disorder. There are a number of other harms associated with opioids, so these are not related to the overdose issue, but bothersome harms or troublesome harms when people are taking the medications. This is, again, from a review that we did. Discontinuation due to adverse events more than doubles with opioids versus placebo. The relative risk is 2.25. For nausea, the risk increases, again, more than twofold. For vomiting, it increases more than threefold. For constipation, the same, more than threefold increase. Somnolence or sleepiness is about a threefold increase. Dizziness increases. The relative risk there is 2.66. And for pruritus or itching, there's more than a threefold increase. Hyperalgesia, which is a term that refers to a paradoxical increased sensitivity to pain, can also occur in people who are taking opioids chronically, usually people who are on higher doses. Hypogonadism, falls and fracture. There are some evidence indicating increased risks of these other outcomes, but data are relatively limited. It's usually observational studies, and the causality is less clear. All of the stuff in the table above are from randomized controlled trials. So given everything that we've seen about opioids, the benefits, which appear to be pretty small, and the potential harms, including risks of things like overdose, other side effects, and potential for opioid use disorder, it all points to using opioids judiciously and only as part of an overall outcome. It's important to understand chronic low back pain from a biopsychosocial framework. Again, the benefits of opioids appear small. There are short-term harms that, you know, people are very familiar with, the constipation, the sleepiness, the nausea, etc. But there is also potentially serious harms up to unintentional overdose. Opioids are not generally first-line therapy. It's important to be clear with patients that opioids generally do not eliminate pain. As we saw in the previous slides, the difference between placebo is about one point on a 0 to 10 pain scale. So we're talking about somebody without opioids might be at a pain score of 4 or 5, and the opioids would put them on average about one point better than that. In addition, it's important to be clear that the opioids are really just part of a comprehensive management plan. The biopsychosocial framework is important because it tells us that biological factors are important, but so are psychological and social factors. And using an opioid does not address the psychological and social contributors to pain that are often present. Therefore, it's important to use opioids in conjunction with therapies that actually address these psychosocial factors. For acute low back pain, it's important to remember that the natural history is very favorable. About 85% of patients improve substantially in the first month. Some studies indicate that opioid use in acute pain is associated with poor functional outcomes and increases the likelihood of subsequent long-term use, and it's generally not recommended. As I mentioned earlier, the new OPAL trial, that's O-P-A-L, was just recently published, the first placebo-controlled trial of opioids for acute low back pain, and it showed no beneficial effect. So I think that underscores the points I'm making here. Selective opioid use may be considered for chronic low back pain in patients who have not responded to first-line medications, such as NSAIDs or duloxetine, on a time-limited basis for short-term symptomatic relief. The 2016 CDC guideline, the 2022 guideline has actually come out, though many of the recommendations are similar. The first recommendation is that non-pharmacologic therapy and non-opioid pharmacologic therapy are preferred for chronic pain. Consider opioid therapy only if the expected benefits are anticipated to outweigh the risk to the patient. If opioids are used, combine with appropriate non-pharmacologic therapy and non-opioid pharmacologic therapy. The 2017 American College of Physicians and American Pain Society guideline, this was based on reviews that we conducted that were funded by AHRQ. The guideline is below, that's actually from the American College of Physicians. This is an update to a prior guideline that we had led for both the American College of Physicians and the ACP. The 2017 ACP guideline puts an emphasis on non-pharmacologic over pharmacologic therapies, particularly for chronic low back pain. It includes stronger cautions regarding the use of opioids. It no longer recommends acetaminophen for acute low back pain because of evidence showing that it is not effective. And it recommends the use of several active mind-body interventions, including yoga, tai chi, and mindfulness-based studies. Mindfulness stress reduction, excuse me. So here's the management approach to low back pain. The approach is to emphasize self-care and improve function. So don't focus exclusively on pain, but also how people can improve their function. We advise patients to remain active, to utilize coping strategies to help manage their chronic pain, and use relaxation techniques. We think that active therapy should be the core approach. This includes exercise therapy, cognitive behavioral therapy, yoga, mindfulness, and interdisciplinary rehab, which typically combines exercise therapy and psychological approaches and others. It's critical to identify and address the psychosocial contributors to pain. These include depression, anxiety, PTSD, maladaptive coping behaviors, which include fear avoidance, catastrophizing, sleep disturbance, and stressors. Also, CBT, pharmacological therapy, and consider referral for additional specialty assistance if needed. We think it's important to utilize other non-pharmacological therapies, such as spinal manipulation, acupuncture, and massage, which have been associated with some beneficial effects in patients with chronic low back pain, and may reduce the need for medications. Medications are generally considered as adjunctive therapies. NSAIDs are first-line. As I mentioned, a recent RCT showed no benefits of acetaminophen for acute low back pain. Second-line options show that skeletal muscle relaxants for acute low back pain and antidepressants for chronic low back pain are reasonable second-line options. We reserve opioids only for patients who don't respond to first-line therapies or in selected cases with very severe symptoms. So one of the issues in patients who present with acute low back pain is trying to understand who will go on to develop persistent disabling low back pain. As we mentioned previously, most patients recover quite quickly from acute low back pain, but a small proportion do go on to develop chronic low back pain, which can have severe impacts on function, quality of life, and ability to work, and is very difficult to treat. So understanding who may progress to chronic low back pain can help us in terms of tailoring or intensifying our therapy. This is from a review that we conducted that was published in JAMA. This is part of the rational clinical exam series. The key predictors were actually primarily psychological and functional factors. So people who reported non-organic signs, so signs that did not correlate with anatomic or scientific understanding of back and back pain, that was associated with a threefold increased likelihood of developing persistent disabling low back pain. Having maladaptive pain coping behaviors, this means that they have catastrophizing, which refers to a coping behavior pattern where people think that everything is going to just get worse and worse and that it's, you know, not something that's totally completely out of their control. That's one maladaptive pain coping behavior. Another common one is what we call fear avoidance, which means that people are so afraid of their pain and making their pain worse that they stop doing regular, you know, normal activities. So maladaptive pain coping behaviors increase the likelihood of developing persistent disabling low back pain 2.5 times. Having functional impairment and baseline increases the risk about two times. Having psychiatric comorbidities about 2.2 times and low general health status about 1.8 times. There are several variables related to the work environment, presence of severity and presence of baseline pain, presence of radiculopathy, which all increase the likelihood by about 50%, but not by as much as the factors higher up in the table. Having a history of prior low back pain episodes and several demographic variables such as age, sex, overweight, smoking, education are not predictive. In terms of targeting patients at risk for chronicity, the START-BAC trial was published in 2011. It included 1,573 UK patients with low back pain, either with or without radiculopathy. The trial randomized patients to stratified care based on prognosis, they were categorized as being low, medium, or high risk for developing chronicity or usual care. In patients in the stratified care arm, the low risk group, the intervention they received was an educational video and a booklet. In the medium and high risk group, the interventions were referred for psychologically informed therapy, given by physical therapists who received three or nine additional days of training. This study found that the stratified care approach was more effective than usual care for function by about 1.8 points at four months and by about 1.1 point at 12 months, it was also cost effective. Unfortunately, a trial that attempted to implement START-BAC in the US found low uptake, indicating that there may be more challenges utilizing a approach to care like this in the United States. But as again, the evidence does indicate that a stratified care approach can lead to improved outcomes if it's utilized. This just shows the START-BAC screening tool that was used in the START-BAC trial. So it's a nine-item instrument. Each one is scored zero or one except for the last one where there's several options also scored zero. And then the total is scored, the score ranges from zero to nine. And there's a sub score for questions five to nine. And then you can see how this is used. So if the total score is three or less, the patient is classified as low risk. If the score is four or more, you take the psych score, which are items five to nine and see what the score was on those five items. If they score three or less on those five items, they're classified as medium risk and four or more, they're classified as high risk. And then again, depending on which risk category you're triaged into, you receive different intensity of treatments. In terms of selecting appropriate risk assessment is critical to determine the intensity of follow-up and monitoring. Assessment of abuse potential is required in all patients being considered for opioids. The strongest predictor is having a personal or family history of substance use disorder. The opioid risk tool allows clinicians to categorize patients as low, medium, or high risk for aberrant drug-related behaviors based on a simple point system. Additional validation is needed for the opioid risk tool as well for other risk assessment instruments. In general, if we see that a patient is high risk using an instrument, we would want to avoid opioids. In people who are medium risk, at least consider alternatives or utilize strong mitigation strategies and always address identified risk factors. It's important to also consider potential benefits and other potential harms such as respiratory depression in patients with sleep apnea when making the decisions to start opioids. So the opioid risk tool, this just shows the opioid risk tool. This can be administered prior to initiating therapy in order to predict opioid misuse on long-term therapy. In the original study, patients who scored zero to three were classified as low risk and had a 6% likelihood of misuse of opioids or using opioids in non-prescribed ways. Four to seven was a moderate risk, and they had a 28% risk of using opioids other than prescribed. And people who scored greater than eight were at high risk, over 90%. And you can see that there's a point system. Much of the tool focuses on family and personal history of substance use. Age is also one of the factors, history of preadolescent sexual abuse in females, and then presence of psychological disease in both groups. In terms of initiating and titrating of opioids, the initial course of opioids should be viewed as a short-term therapeutic trial. The decision to proceed or continue with long-term opioid therapy should be a conscious one. It's important to determine achievable functional goals in order to assess benefits and to not continue long-term opioid therapy in patients who are not benefiting. The principle is to start at low doses and titrate cautiously to reduce the risk of accidental overdose, again, in people who are naive to opioids and have not yet developed tolerance. And as mentioned before, people, if methadone is used, it should be used with a lot of caution. Methadone has a long and unpredictable half-life, which can increase risk for accidental overdose. It's important to set functional treatment goals. When we're talking about these types of goals, we're talking about goals that are actionable, measurable, and achievable. We should perform regular assessments of whether patients are achieving the treatment goals in order to help guide our treatment decisions. Again, if the opioids are not helping the patients to meet their goals, that indicates lack of benefit and may warrant consideration of discontinuation. So an example of a goal that is not achievable is I want to be pain-free. We know that that's not going to happen in the vast majority of patients prescribed opioids. What may be actionable, measurable, and achievable is I want to be able to walk my dog 20 minutes a day, four to five times a week. That's something that we can work with the patients to slowly increase their ability to walk, utilize pharmacologic and non-pharmacological therapies to help get them there, and help them with strategies, psychological strategies, coping strategies, and others to help them to be able to improve their function in the way they want to. Dose escalations. So opioids for chronic pain are often prescribed with no ceiling dose. Evidence shows that the risk of overdose begins to increase at less than 20 milligram morphine equivalents per day and continues to rise in a dose-dependent fashion. We have very limited data on the effectiveness of opioids at higher doses. Patients who do not respond at lower doses often will not respond at higher doses. Recommendations are to only prescribe higher doses in patients with clear improvements in pain and function and with close monitoring. The 2016 CDC guideline recommended caution with doses over 50 morphine equivalent per day and to avoid over 90 morphine equivalents per day, but the new 2022 CDC guideline does not have those types of thresholds. It just says to try to use lower doses as possible. It's important to note that even in the 2016 CDC guideline, these were not hard or inflexible thresholds. The guideline makes it clear that use of higher doses can be done, but it requires a careful individualization based on the assessment of each patient. If doses are increased, those increases should be done slowly with follow-up after changes. Some evidence shows that having dose threshold policies in place, for example, certain states or other entities may limit the doses of opioids that can be used, may reduce high dose prescribing rates and overdose, but there's also potential harms from abrupt or unnecessary dose reductions. These types of policies really should be very cautious and may not strictly follow the guideline, which again, the 2022 guideline does not recommend specific dosing thresholds. In terms of selection of opioids, there's no evidence that long-acting opioids are safer or less prone to abuse than short-acting opioids. Long-acting opioids may result in fewer drug peaks associated with euphoria, but decreased risk of addiction or abuse has not been demonstrated. There is no evidence that round-the-clock scheduled dosing is safer or less prone to abuse than PRM dosing, and use of round-the-clock scheduled dosing may contribute to the development of tolerance and subsequent dose escalations. Recommendations are to initiate treatment with short-acting opioids. These are safer in opioid-naive patients. It's easier to titrate opioids with short-acting duration of action than long-acting opioids. Clinicians can transition patients to long-acting opioids, but there is no compelling reason to do so in patients who have no aberrant behaviors and are having a good response to short-acting meds. Risk mitigation strategies. So, giving informed consent is required in all patients. Patients need to understand what the benefits as well as what the potential harms are and how they may be able to help manage those harms themselves. A long-term opioid therapy management plan is recommended by guidelines. Components include follow-up expectations, having a single prescriber for opioids, as well as a single dispensing pharmacy, no early or off-hour fill requests, what the expectations for monitoring are, including coming in for periodic urine drug screens, use of non-opioid therapies, functional goals, and indications for tapering or discontinuation. All of this helps to define the expectations as well as to help assist other providers who may end up covering for the patient when you're not available. Follow-up is generally recommended every three to six months, maybe more frequently in high-risk patients. In higher-risk patients, you might consider dispensing weekly or bi-weekly rather than monthly. Some data suggests that shorter duration between prescription refills, so smaller amounts dispensed, are associated with shorter time off of work. Urine drug tests are one of our risk mitigation strategies. We know that self-report can be unreliable when we're asking people about medication, drug use behaviors. Behavioral observations can only detect some of these types of problems. What urine drug tests do is they provide objective information regarding whether patients are adherent to the opioid plan of care, whether patients are adherent to the opioid plan of care, whether they are using or not using illicit substances or unprescribed medications, and it may help to improve adherence to the opioid plan of care. It's really about keeping patients safe by understanding what medications they may be taking, in particular medications that you're not prescribing that may impair their safety. Urine drug tests can be performed at baseline and periodically. General recommendations are to do these one to two times a year for low-risk patients and three to four times a year for higher risk. They can be done in a variety of approaches, so they can be random, scheduled, you know, again, once a year, once every six months, and or when concerns arise, we don't have data showing what the best strategy is. It's useful to discuss the expected findings with the patient prior to testing so that if you do have unexpected findings, they know why, you know, what was supposed to be there. If the patient disputes the findings, it is important to note that sometimes we do see unusual metabolites or other patterns. Sometimes there's some reports that, you know, a certain drug is showing up in the urine drug screens. That's possible contamination or something else is going on, so it can be helpful to consult with a local toxicologist or clinical pathologist if the patient disputes the findings. Screening tests require confirmation, usually done with gas chromatography. For some opioids, you may end up running a specific test. Prescription drug monitoring programs are a very useful tool. These are available now in almost all states. More than 20 states require clinicians to access prior to prescribing controlled substances. Studies show that the use of PDMPs can identify cases of diversion, provider shopping, and flag unsafe prescribing practices. However, we do lack evidence on positive impacts on clinical outcomes, i.e. reducing overdose risks. Use of PDMPs is variable and has been suboptimal, though it has improved. PDMPs vary in who can access them. These are, you know, state-by-state, though some states do have cooperative agreements. The functionality of the PDMPs is variable. Another risk mitigation strategy is to avoid concomitant opioids and benzos. Concomitant benzodiazepine use is associated with markedly increased risk of opioid overdose. Other medications with respiratory depressant effects may also be associated with similar risks, so things like zolpidem and other sedatives. It's important that if somebody is on chronic long-term benzodiazepines that the benzos need to be tapered gradually. Withdrawal can be severe and challenging with benzodiazepines. We do have other evidence-based therapies for anxiety, like cognitive behavioral therapy, antidepressants that are approved for treatment of anxiety, and other non-benzodiazepine medications. If necessary, coordinate care with mental health professionals and or consider referral. Naloxone. This is an opioid antagonist that can rapidly reverse opioid overdose. Naloxone is useful because most overdose episodes are witnessed. So naloxone can be administered to somebody who is experiencing an overdose. It's been, so by a bystander or somebody who's in the room, it's been found to be highly effective in addiction settings. We have limited evidence of effectiveness in chronic pain settings, though one observational study found that co-prescribing of naloxone to primary care patients prescribed opioids was associated with 47% fewer opioid-related ED visits at six months and 63% fewer visits at one year compared with no naloxone. CDC recommends naloxone for all patients on at least 50 morphine equivalents per day or who have other risk factors for overdose and to consider it for all patients prescribed opioids, not just those at higher risk. Naloxone is available in FDA-approved intramuscular and intranasal formulations. The IM formulation is no longer being produced. I believe a new intranasal formulation was just approved. Also injectable naloxone used off-label for intranasal administration using an atomizer is often done because it's less expensive. Tapering opioids. It's important to periodically perform a risk-benefit assessment to inform tapering decisions, including the following factors, presence of opioid use disorder and misuse behaviors, prior overdose episodes, the overt opioid dose, failure to improve or meet treatment goals, including pain as well as function, and use of concomitant respiratory depressants such as benzodiazepines. Initiate the taper when benefits are outweighed by risks. Offer taper for patients at high doses, which by themselves represent a risk factor, but decisions regarding taper should always be based on an individualized assessment of benefits to harm. Some patients who are benefiting, even if they're on higher dose, it may be warranted to continue them on their current dose with appropriate monitoring. Studies do show that patients often report unchanged or improved pain with taper. Again, the taper should not be done too quickly and it needs to be done with appropriate support to ensure that there aren't adverse impacts from doing the taper. There is some evidence on outcomes of opioid tapering. This shows that pain function and quality of life may improve with opioid dose reduction. We don't have sufficient evidence at this time to understand the optimal tapering protocol. Some patients may require very prolonged tapers. The principle behind the tapers is to focus on getting the dose lower and reducing risk, not necessarily focusing on having to reach a specific dose threshold. It's better to get somebody down and not focus so much on getting somebody to say zero if they start to have a lot of issues once you get to lower doses and trying to taper further down. While tapering, it's important to continue to manage pain with non-opioid therapies. Our strategies for difficult tapers are to slower the taper, consider referral to interdisciplinary pain programs or to addiction specialists, utilize buprenorphine to assist with the taper, and utilize taper support programs. Tapering may unmask opioid use disorder, so it's important, especially in patients who are having difficulty tapering, to assess for opioid use disorder and treat appropriately if it's present. Opioids for acute low back pain. Opioids are generally considered effective for acute pain, but evidence indicates that opioids may be no more effective than an NSAID alone for acute pain. And again, the new OPAL trial, O-P-A-L, showed that opioids were no more effective than placebo for acute back or neck pain. We also know that use of opioids for minor pain is associated with increased risk of long-term use, and prescribing excessive quantities of opioids for acute pain can result in leftover opioids if the pain resolves like it normally does. This can serve as a source of diversion and unprescribed use. So, we recommend more judicious use of opioids for acute pain. Some have started to question whether opioids should be used at all, for acute pain. I'll just say that in the OPAL trial, the average duration of pain was about 21 days, and people had moderate levels of pain. So, there might be some people with very severe hyperacute pain, meaning pain for, you know, several days or less, and they may, there might be some benefit, though again, the studies are not available yet. So, there may be some benefits but in those cases, there may still be a limited use of opioids. If used, limit opioids to a three to seven day supply for most acute pain. Research on doses of opioids prescribed and used for acute low back pain is ongoing. So, opioids and low back pain, in summary, I consider opioids only in the context of an overall pain management plan and based on an individualized risk assessment. Opioids are not recommended as first-line treatment. Evidence on effectiveness for low back pain suggests small short-term benefits and increased short-term and bothersome harms. There's potential for serious harm, including overdose and opioid use disorder. Consider only after monitoring, after performing risk assessment and with appropriate monitoring and recognize that there's, there are dose-dependent overdose risks with unclear benefits of higher doses and the need to make decisions to increase or continue higher doses based on an assessment of benefits and harms in individual patients. So, going back to the case, Mr. S has no personal or family history of substance abuse. Remember, this is a patient who has had low back pain for several months, which is slowly getting worse. He's walking, he's taking a cart now when he golfs instead of walking like previously. He has no history of depression or other psychological disorders, no serious comorbid conditions that are contraindications to opioid therapy. His opioid risk tool score is zero. The urine drug test is negative and his assessed risk is low. At the eight-week follow-up, the pain was still at five to six out of ten. At that time, because he's at low risk, we decided to initiate low-dose opioid therapy, which was oxycodone five milligrams twice a day. That's 15 milligrams morphine equivalents per day. The 12-week follow-up, his pain had decreased to four out of ten with no concerning behaviors. The plan at that time was to continue the opioid therapy at the same low-dose and then to follow him up in two months. We had a set goal of walking 30 minutes four times a week, a longer-term goal of walking nine holes of golf. Exercise therapy was recommended. We recommended continuing his usual low-impact activities, and the low-dose opioids were continued. At four-week follow-up, his pain had decreased from four out of ten to three out of ten. He's engaged in exercise therapy. He was able to walk 20 to 30 minutes four times a week, so that was an improvement as well. Rather than increasing the opioid further, which I'd say he's demonstrated a favorable or positive response to the opioid, we added a non-opioid medication, duloxetine. That was the last slide for the module. Here, there's a number of references that you can refer to for further details, and then some online references as well. I'd like to inform you of two resources offered through PCSS that may interest you. First, PCSS's mentor program is designed to offer mentoring assistance to those in need of more one-on-one interactions with one of our colleagues to address clinical questions. You can request a mentor from our mentor directory, or we are happy to pair you with one. To find out more information, please visit our website using the web link noted on this slide. Second, PCSS offers a discussion forum, which is comprised of our PCSS mentors and other experts in the field who help provide prompt responses to clinical cases and questions. We also have a mentor on call each month. This person is available to address any submitted questions through the discussion forum. You can create a new login account by clicking the image on the slide to access the registration page. We also have a mentor on call each month. This person is available to access the registration page. This slide simply notes the consortium of lead partner organizations that are a part of the PCSS project. Finally, please reference this slide for our contact info website and Twitter and Facebook handles to find out more about our resources and educational offerings. Thank you.

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