Hi, this is Roger Chow. I'll be presenting the module on Opioid Therapy for Pain, including an evidence review. So, the goals of this session are for participants to review the evidence on use of opioid therapy for chronic pain, and then to be able to assess the risks and benefits of long-term opioid therapy for chronic pain, as well as factors associated with prescription opioid overdose and misuse. Just as a note, best practices to reduce risks related to prescription opioids are discussed in a separate topic. So, starting with a case, this is a 53-year-old female transferring care because her PCP is leaving practice. She has shoulder and hip pain, secondary to avascular necrosis. She's undergone prior shoulder replacements, hip decompression, as well as hip replacement. She also has fibromyalgia, non-radicular low back pain, chronic headaches, depression and fatigue, gastroparesis, and irritable bowel syndrome. She's on morphine, immediate release, 30 milligrams, five tabs, so that's 150 milligrams every eight hours, plus oxycodone, five milligrams, eight tabs, total of 40 milligrams every six hours. This calculates out to a morphine equivalent dose per day of 690 milligrams. She's on modafinil, 20 milligrams daily. That's for the fatigue, and then reports her pain as six out of 10 on average with some day-to-day fluctuation. She can carry out activities of daily living with pain, limited exercise, she says primarily because of pain, no aberrant drug use behaviors reported. So, we'll come back to that case at the end of the presentation. Just in terms of some background, I think everyone knows that chronic non-cancer pain is highly prevalent. It's associated with substantial burdens. Estimates vary, but indicate that up to a third of adults report some chronic non-cancer pain. Opioids have become commonly prescribed for chronic non-cancer pain. This occurred roughly between the years 2000 to 2010 or so is when we saw the most rapid increase. About 5% of US adults report use of long-term opioid therapy, and I think it's important to recognize that the US is different from most other countries. We represent about 5% of the world's population, but we use about 80% of the world's supply of opioids, almost all of the hydrocodone. Opioids are different from most other medications, so all medications are associated with potential harms and opioids are no different, but opioids also have societal harms, and these are related to their addiction potential. There's large practice variations in use of long-term opioid therapy. This usually indicates uncertainty about use or concerns about safety. This slide is from the CDC. This shows parallel increases in opioid sales, deaths, and substance abuse diagnoses. The green line shows that US opioid sales quadrupled from 2000 to 2010. You can see deaths rose in parallel, and then also treatment admissions for substance use disorders. Since 2008, there have been over 15,000 deaths per year related to prescription opioids. This exceeds MVA deaths in most states now. This shows some more recent data. Since 2010, the number of overdose deaths from prescription opioid pain relievers has leveled off, though the COVID data are concerning and are still evolving. We don't have the full data set yet. But prior to 2020, at least, there were signs that things have plateaued. Unfortunately, we've seen, even as deaths related to opioid analgesics have plateaued, we've seen an increase in deaths related to heroin, and this slide just goes through 2012 or 2013, but even more recently, the sharpest spike has been related to illicit fentanyl and fentanyl analogs. This slide illustrates some of the societal, you know, ramifications of opioids. So this is based on a survey that's done of adolescents and young adults, and what you can see is, you know, from 2002 to 2010, if you took adolescents aged 12 to 17, about 8% reported using a non-medical pain medication, so a medication that wasn't prescribed for them in the last year. So that's about 1 out of every 12 adolescents. If you look at 12th graders, it increases to about 1 out of every 10 or 11 or so, and then among young adults, 18 to 25, it's about 1 out of every 8. So this is, you know, obviously not something that happens with most other drugs. People don't go into the medicine cabinet and use, you know, their parents' blood pressure medication or cholesterol medication. This is related to the, you know, unique properties of opioids in terms of the addiction potential and, you know, euphoric effects as well as the pain effects. This slide, I think, illustrates that even though the most recent spikes have been related to primarily to use of illicit opioids, that, you know, it's really difficult to disentangle prescription from illicit opioid use. So if you go back to the 60s and 70s, the vast majority of people using heroin, if you asked them what their first opioid of abuse was, they would say that it was heroin. They started by using illicit opioids. That pattern has reversed so that now people who use heroin, if you ask them their first opioid of abuse, the majority report that it was a prescription opioid. So the way that people are introduced to opioids now is really different and primarily from the prescription route. In terms of prescribing trends, since 2010, opioid use for chronic pain increased from about 8% to 16% of patients. Use of more potent opioids also increased from 2% to 9%. These trends have been observed across age group and in men as well as in women. There's been increased use of Schedule II opioids with the greatest increase in daily doses occurring in prescriptions of Schedule II opioids. I think it's worth kind of pausing here to think about how did we get to this situation where opioids are so commonly used and we've seen the data on overdose and other adverse effects. I think there was a number of factors that played a role here. There was a perceived and real undertreatment of chronic pain. This led to laws or regulations being passed in a number of states to allow use of opioids for chronic pain or to be more permissive. There's data taken from palliative care settings, which were applied to chronic pain outside of palliative care settings. In those studies, there was a low risk of abuse observed. This is a quote from a paper by Russ Portnoy. He said, patients rarely demonstrate euphoric responses to opioid drugs and neither allelgic tolerance nor physical dependence is a significant clinical problem. There are also case theories describing benefits of long-term opioid therapy for chronic pain with low rates of abuse, addiction, or other serious adverse effects. It's important to recall that most of these use low doses. Many of them were actually in hospital settings and not necessarily applicable to long-term care, but they were kind of taken as evidence that opioids could be used safely there as well. There was a strong belief, actually, that there was, in the fact that there was no ceiling dose for opioids, this is common practice in palliative care settings that you can increase the dose as long as you do it slowly. People do fine. And the reason to do it is because of development of tolerance. And so this is, again, a quote from Russ Portnoy. He said, escalation of the opioid dose until either adequate analgesia occurs or intolerable and unmanageable side effects supervene as standard practice in cancer pain management. And again, this was translated to the chronic pain non-cancer setting. There's also an emphasis on round-the-clock dosing using sustained release formulations. This coincided with the release of sustained release oxycodone, which became extremely widely used. So really a confluence of factors, I think, led to these pretty marked changes in use of opioids and kind of led to the situation that we're in now. Looking at the evidence on the effectiveness of opioids for chronic non-cancer pain, most of the data are short-term follow-up. So this is, you know, one to three months or less versus placebo. The main difference is actually not very large. It's less than one point on a zero to 10-point pain scale. So lower than I think most people would predict or expect. You know, if you ask, I think, most patients, you know, what, how effective they think opioids are, they would probably say, you know, at least 30 to 50 percent. But again, on average, it's less than one point on a 10-point pain scale. In terms of a pain response, so this is the likelihood of achieving, you know, either a 30 or 50 percent improvement. Opioids are associated with increased likelihood of pain response. So some people seem to do better than others, where some people don't respond at all, but there is an increased likelihood of having a significant pain response. In terms of function, the effects are pretty small. So that's a standardized mean difference of minus 0.22. That's considered pretty small. That probably translates to about, say, a one to two-point difference on the Roland Morris Disability Questionnaire. That's a 24-point scale. The studies indicate little incremental benefit with increased doses. If you compare opioids versus non-opioids, so for example NSAIDs or other non-opioid medications used for analgesia, there's no differences in pain intensity, likelihood of pain response, or function, and this is based on 11 to 14 trials. For longer-term follow-up, we really don't have placebo-controlled trials still. There's one one-year trial of opioids versus non-opioids. This is the SPACE trial. It found no difference between step therapy with opioids versus step therapy with non-opioids and function. In fact, opioid therapy was associated with higher or worse pain intensity by about half a point. In terms of the evidence and limitations of the evidence, these studies typically have high loss to follow-up. They typically exclude patients at higher risk for addiction or overdose, people with psychological comorbidities, and people with serious medical comorbidities. There's limited evidence on commonly treated conditions like fibromyalgia, headaches, and others. We don't have any trials comparing long-term opioid therapy versus cognitive behavioral-based exercise therapy or interdisciplinary rehab. Some things we still don't know. I'd say that the short-term benefits and the way that the trial selected patients probably are the best-case scenario, and we wouldn't expect the results to be better if they did include some of these other populations, which are commonly encountered in clinical practice and typically more difficult to treat. Some more detail about opioids versus non-opioids. This is the SPACE trial I mentioned earlier. This was step therapy. They started with opioids versus initial non-opioid therapy, patients with chronic low back pain or osteoarthritis pain. This is a VA trial conducted in primary care with 240 patients. It was open-label for patients and clinicians. Assessment of outcomes was masked. All patients received individualized medication management using a collaborative telecare pain management model. The average opioid dose ended up at 26 milligram morphine-equivalent dose per day with step therapy starting with opioids versus 1 milligram in the non-opioid arm. At 12 months, there was no difference in function between groups. As mentioned, pain was slightly worse in the opioid group, and opioids were associated with more adverse symptoms, though there was no deaths or cases of opioid use disorder. This shows the results for pain intensity. You can see at the start of the trial, the opioid and the non-opioid groups had equivalent average pain intensity. At the end of the trial, the non-opioid group actually had slightly lower or better pain intensity. Then you can see for function, the results are basically identical. There's also data on harms, short-term harms of opioid therapy. These list common harms, so discontinuation due to adverse events, various GI harms, so nausea, vomiting, constipation, some of the CNS effects, like somnolence or dizziness, and then pruritus. You can see in all of these, opioids are associated with increased risk. The absolute risk differences range from 7% to 17% more in the opioid therapy harms. Addiction and misuse, the trials have not been designed to assess these. They actually intentionally enroll people who are not at high risk for addiction and misuse. In observational studies, though, the rates of misuse average between 21% to 29%. The rates of addiction average between 8% to 12%. The reason that there's some variability is that the definitions for these outcomes are inconsistent. Also important, I think, to recognize that these behaviors do vary in curiousness, and just the method used to detect these outcomes have not been well standardized. One study, one pretty large study, 800 patients, that was based on detailed standardized interviews found that 26% of patients reported use of opioids for purposeful over-sedation, 39% reported increase in the dose without prescription to increase the dose, 8% obtained extra opioids from other doctors, 18% used opioids for purposes other than pain, and 12% reported hoarding their pain medication. So all of these, I think, would be considered concerning behaviors. Evidence does identify factors associated with increased risk of overdose or that have been observed in high proportions of overdose. These include misuse behaviors, so some of those behaviors that I just listed in that study on the prior slide, so getting opioids from multiple providers, running out early or losing prescriptions, unauthorized dose escalations, the period right after starting opioids is higher risk, so recent initiation, methadone is associated with increased risk, using benzos plus opioids, substance use, psychological comorbidities, and higher doses. In terms of the overdose dose response relationship, observational studies consistently show an association between opioid dose and risk of overdose or death in patients with chronic pain. The risk starts to increase at relatively low doses and continues to increase. These studies do try to match or adjust for potential confounders available in administrative databases, though, of course, there's some potential for residual confounding. It's also difficult for most of these studies to determine whether patients had chronic pain and the duration of therapy. That being said, the associations, again, appear to be pretty consistent, though the estimates do vary a little bit. So, you see in this first study at 20 to 50 milligrams, so compared to less than 20 milligrams, the hazard ratio is 1.4. This goes up to 8.9 at over 100 milligrams per day. You see in the second study, those estimates are actually fairly close, but then in the third study, the estimates, there's still a dose response, but the estimates increase from 1.3 to 2.9. There's other harms of opioids. These include hyperalgesia. This refers to a paradoxical increase sensitivity to pain, typically appears at higher doses. The prevalence of this condition, risk factors, and clinical significance are not well understood. It's also difficult to distinguish from somebody simply having, you know, worsening of their underlying pain condition. Hypogonadism has also been reported. This is primarily based on cross-sectional studies. One study showed an association between use of opioids and increased use of testosterone and ED meds. Some, there's also limited evidence on increased falls or fracture risk, increased risk of myocardial infarction, and poor functional outcomes. So all this taken into account, guidelines have been published on use of opioids for chronic pain. I think in terms of initiating and titrating opioids, it's important to recognize that opioids are not first-line therapy for chronic pain. The benefits are not larger than other therapies that we have available, which should be tried first based on safety profile. In appropriately selected patients who don't respond to non-opioid therapy, opioids may be considered. If they're used, the initial course should be thought of as a short-term therapeutic trial. This is critical. Don't continue opioids in patients who aren't benefiting. They need to be reassessed, and this decision needs to be taken consciously. Unfortunately, a lot of patients are started on opioids, and this doesn't happen even if they're not benefiting, and they, you know, continue on them, and then they run into issues with tolerance and withdrawal, et cetera. The principle is to start at low doses and to titrate cautiously. There's insufficient evidence to recommend short-versus-long-acting opioids or around-the-clock versus PRN dosing. The potential benefits of long-acting around-the-clock dosing are unproven. It's thought that this might result in more kind of regular levels and cause less of the ups and downs, which may, you know, predispose towards addiction, but this hasn't been proving. There are some potential harms of around-the-clock dosing, which include increased risk of hyperalgesia, developmental tolerance, and endocrinologic adverse effects. Initiation with long-acting opioids is associated with increased risk of overdose, so we recommend initiating with a short-acting agent. Methadone and fentanyl are not recommended as first-line options because these formulations are less predictable. There's more complicated dosing and more complicated pharmacokinetics. Buprenorphine for chronic pain may be useful in higher-risk patients. Evidence is lacking to show improved safety, but theoretically, lower respiratory and overdose risk. Higher-dose buprenorphine formulations are approved for treatment of opioid use disorder and are off-label for pain. There are some lower-dose formulations that can be used on-label for pain. Methadone, this is a synthetic opioid used for treatment of addiction and pain. There were increased methadone deaths reported nationwide when this medication started being used more regularly. It was essentially used as a less expensive long-acting opioid. In 1999, there were 800 deaths. In 2008, there were almost 5,000. The deaths associated with methadone were disproportionate to the degree to which it was being used, so even though methadone accounted for 1.7% of opioid prescriptions in 2009 and 9.0% in 2010, it was involved in 30 to 40% of deaths. One of the reasons for this is a long half-life of methadone, which is 15 to 60 hours and can be up to 120 hours. This translates to 12 days or almost two weeks to a steady state when you have a 60-hour half-life, so it's critical with methadone especially to start at low doses and to titrate up slowly, so the recommendations are usually to start at 2.5 milligrams every eight hours. Methadone at high doses is also associated with greater QTC interval prolongation. There's a high proportion of, most cases of TORSADS inpatients prescribed methadone wherein people prescribed doses over 200 milligrams per day. ECG monitoring at baseline at higher doses is recommended, and it's also a little tricky to convert morphine to methadone. People don't always realize that the conversion ratios actually vary. It gets higher at higher morphine doses when you're converting, and this is due to incomplete cross-tolerance, so if you're not aware of this, you might put somebody on a dose of methadone that's too high to replace their morphine. This slide just illustrates the pharmacokinetics in that it takes about four half-lives or so for people to reach steady state, and again, if you have a half-life of 60 hours, it's gonna take 12 days or almost two weeks to reach steady state, so the drug levels are continuing to accumulate over that entire period. This slide shows two ECGs, so the first one, the QTC interval is prolonged. It's at 626 milliseconds, and then after starting the drug, this degenerates into torsades, so that's a ventricular rhythm. It can be perfusing, but it can also degenerate to a non-perfusing rhythm or turn into V-fib arrests, so this can be concerning. It doesn't appear to be really common, but again, this is one of the differences between methadone and other opioid analgesics, and then this slide just illustrates what I was showing before, that the conversion ratios go up if you're on higher doses of morphine, and it's important to be aware of this if you're converting patients from morphine to methadone. Fentanyl, the absorption and pharmacodynamics of transdermal fentanyl are complex. Again, we're focusing on prescription fentanyl here, not the illicit analogs out there on the market. Because of the complicated pharmacodynamics, the recommendations are to gradually increase the dose. The levels go up slowly over the 72-hour dosing interval. The absorption can vary based on things like application, like how hot it is or application of external heat. People can also get confused because fentanyl is in micrograms per hour instead of milligrams. So if you do use fentanyl, it should be prescribed to clinicians who are familiar with its use and complexities. We don't think there's an advantage in most patients to use fentanyl instead of oral agents that people are more familiar with. In terms of dosing, there's no theoretical ceiling with opioids, but little evidence to guide prescribing at higher doses. We think at higher doses there's additional risks, unclear benefit, and the need to keep upping the dose may be a marker for opioid use disorder or diversion. Higher doses, as we showed, is associated with increased risk of overdose. And it's quite unclear, actually, if patients who don't respond at relatively low doses will respond at higher doses. At least clinically, there seem to be people who are opioid non-responders, meaning they don't seem to respond. If they don't respond at a low dose, they also don't respond at higher doses. Definitions of higher dose have varied and continue to evolve. The trend from a policy standpoint has been to apply lower dose threshold based on new evidence on dose-dependent overdose risk. The 2009 American Pain Society, American Academy of Pain Medicine guideline defined greater than 200 morphine milligram equivalents per day as higher dose. But the 2016 CDC guideline recommended caution at 50 to 90 milligrams per day and to avoid doses greater than 90 a day. Those aren't hard thresholds. So it should be, I just wanted to emphasize that, that the CDC guideline actually does say higher doses can be used, but to be cautious about it and to apply closer monitoring. In terms of mitigating risks, at higher doses, patients should be counseled about risks, given an opportunity to taper if they wish, more frequent or intense monitoring, considering, consider tapering if not achieving therapeutic goals, provide naloxone and opioid antagonists in conjunction with overdose education, and avoid co-prescribing other medications that may increase risk of overdose, like benzodiazepines, other sedatives, and gabapentinoids. In terms of high-dose opioid therapy prescribing patterns, a small proportion of patients account for the majority of opioids that are prescribed. In one study, 5% of opioid users accounted for 48 to 70% of total use. Factors associated with high-dose therapy include presence of substance use disorders, presence of mental health disorders, use of sedative hypnotics and multiple opioids, higher health service utilization, and multiple pain problems and high levels of medical and psychiatric comorbidity. These all indicate a phenomenon that we refer to as adverse selection. This means that people who are at the highest risk are actually more likely to receive high-dose opioids, when generally we'd like it to be the opposite. From a clinical standpoint, I think it's important that, yes, these are patients who are in high distress. They often have severe pain. But when people have a lot of psychosocial risk factors, the approach should be to address those risk factors and to address the distress, not necessarily increasing the dose. There's a number of steps that can be taken to mitigate risks. We'll be going through these in the next slides. They're just listed here. One is to use urine drug tests. So urine drug tests are recommended to help identify risky behaviors that would otherwise be undisclosed. Urine tests are non-invasive. They provide objective documentation of compliance with treatment, including use of or absence of prescribed drugs, non-prescribed drugs, and illicit substances. They have a longer window of detection compared to blood testing. Urine drug testing should be performed at baseline and periodically. The interval may be guided in part by the level of assessed risk. People should also be tested if there's suspected aberrant behaviors and after major changes in treatment. The optimal frequency and usefulness of individualized or random versus routine testing is uncertain. One to two times per year may be appropriate for low-risk patients. Three to four more times for higher risk. Individualized or random testing may miss some abnormal tests, but probably a higher yield and reduced costs. And recognize that patients may have more opportunity to tamper or alter behavior if you're doing routine testing and it's predictable when it's gonna be done. In terms of cannabis use and opioids, there's a high prevalence of cannabis use in patients with chronic pain, either with or without opioids. Evidence shows that states with medical cannabis laws experience slower rates of increase in opioid analgesic overdose death rates compared to states without such laws. This trend reversed such that states with medical cannabis laws experience an overdose deaths rate 22.7% higher than expected in one study. Evidence is limited, but cannabis may have analgesic effects, particularly for neuropathic pain. The effects of cannabis vary depending on THC versus CBD content. THC is associated with psychoactive and intoxicating effects, whereas CBD is associated with medicinal effects. There's little evidence on psychomotor and other effects in patients using cannabis and opioids. The association between cannabis use and opioid and other substance misuse is uncertain. There appears to be increased risk of MBA motor vehicle crashes with cannabis use and caution in patients who are unable to decrease their cannabis use because this could indicate a cannabis use disorder. Opioid deterrent formulations, these have recently been approved by the FDA or are undergoing FDA approval processes. These are designed to be tamper resistant or co-formulated with medications that reverse opioid effects or produce noxious side effects if tampered with. The effectiveness for reducing misuse or substance abuse and improving clinical outcomes is difficult to study. It's likely to be primarily effective in patients who crush or inject opioids. So just be aware that people who overuse pills without crushing or injecting them, these opioid deterrent formulations are not designed to reduce overdose risks in those patients. Some patients who are switched to opioid deterrent formulations may seek other prescriptions or elicit opioids. So there may be some unintended consequences as well. High-risk patients are more vulnerable to opioid abuse, misuse, and addiction. Clinicians who prescribe to high-risk patients must be able to implement additional measures to manage these risks. These include more frequent monitoring, limited prescription fills, consulting with addiction specialists and mental health professionals, using medications for opioid use disorders. If opioids are utilized for pain, opioid deterrent formulations may be helpful and, again, provide naloxone. It's critical to evaluate aberrant drug-related behaviors. These behaviors can vary in seriousness. So it's important for clinicians to judge the seriousness, the cause or causes of the behaviors, the likelihood of recurrence in the clinical context. Some predictors of future behaviors include three or more episodes or a sense that the patient tells you that they're losing control. Serious behaviors include diversion or injecting oral drugs. And the responses can really range. So for less serious behaviors, where we don't think there's a high likelihood of recurrence, it may be patient education and enhanced monitoring. More serious situations may require referral to an addiction specialist or discontinuation slash tapering of therapy. In terms of discontinuation of opioid therapy, patients should be tapered or weaned off of therapy when they engage in intractable drug-related behaviors or drug misuse and diversion, if they're not progressing towards meeting their therapeutic goal, if they're experiencing intolerable adverse effects. In all patients, they should be continued to be managed using non-opioid therapies. And it's important when starting therapy to have an exit strategy. So know what the indications will be for stopping opioid therapy, have plans for tapering or discontinuing, recognize that slow tapers over months or years may be required, provide psychosocial support, and know resources for managing addiction and mental health issues. In terms of driving and work safety, opioids may cause somnolence and coordination without inventation and slower reflexes. Patients should be counseled not to drive or perform dangerous activities when they're impaired. Impairment is more likely when starting therapy, when increasing doses, and when using other drugs with psychoactive effects. There's no evidence that patients on opioids, just because they're on opioids, should be restricted from driving in the absence of signs of impairment. However, state laws vary on reporting requirements and how they view opioids. In some states, there's a presumptive intoxication if you're taking opioids, even if there's no signs of impairment and you've been on them for a long time on stable doses. So clinicians should recognize what the state laws are regarding this and counsel patients appropriately. In terms of opioids for acute pain, opioids are generally considered the most effective medication for acute pain. The recent data indicates that opioids may be no more effective than an NSAID alone for some types of acute pain. In low back pain, adding oxycodone or acetaminophen to an NSAID did not improve pain or function at one week. Opioids are no more effective than NSAIDs for third molar or wisdom tooth extraction. Use of opioids for minor pain is associated with increased risk of long-term use. And prescribing excessive quantities of opioids for acute pain results in leftover opioids. This is a source of diversion and unprescribed use. All of this taken together indicates that we should have more judicious use of opioids for acute pain. If used, usually limit opioids to a three to five day supply for most acute pain. So this may vary depending on the condition and ability to follow up patients, provide refills, et cetera, reassessment and refills. So in conclusion, what is the evidence? The evidence tells us that opioids are associated with modest short-term benefits and increased risk of various opioid-related side effects. The evidence on long-term benefits is limited but indicates no clear benefit versus non-opioid therapy. There's accumulating evidence on serious harms of long-term opioid therapy, including overdose that appear to be dose-dependent. Altogether, the evidence suggests at best a close balance of benefit to harm. For chronic pain, this means we should reserve opioids for appropriately selected patients with persistent pain despite non-opioid therapies. If long-term opioid therapy is prescribed, patients should be monitored and risk mitigation strategies should be utilized. Patients on high doses warrant reevaluation, additional monitoring and follow-up. Doses should be decreased or opioids discontinued in patients who are not improving or whose benefits do not outweigh harm. And for acute pain, use of opioids should be judicious and time-limited with reevaluation in those who have persistent pain or continue to require opioids. So back to our case. So remember, this is a patient who is on quite high doses of opioids, multiple psychiatric and pain issues. It was actually unclear on assessment if she was benefiting from the very high doses of long-term opioid therapy, concerned that the opioids were worsening her GI symptoms. There were no signs of aberrant behaviors. But again, because of the unclear effectiveness and the very high dose with potential risk, a slow taper was initiated over about two years. So the morphine dose dropped from 450 milligrams per day to about 120 milligrams per day. Oxycodone from 160 milligrams daily to five milligrams twice a day. So this translated to 690 morphine equivalents per day to 135. Non-opioid medications were added, duloxetine, 30 milligrams daily, and buspirone and angiolytic, 30 milligrams twice a day. And the patient reported that pain and function, they were still present, but they weren't worse than when on high doses. There was no serious withdrawal. There were some periods of acute pain where the opioids were temporarily increased and with an ongoing goal to get down to less than 100 to 120 milligrams morphine equivalent dose per day. An evidence-informed approach to appropriate use of opioids. Again, the preference is for non-opioid therapies, recognizing that opioids alone don't address the psychosocial contributors to chronic pain. Recognize not all patients are appropriate for opioid therapy. Use risk assessment to inform decisions. If they're used, opioids should be initiated at low doses and titrated slowly. View the initial treatment as a therapeutic trial. Conduct routine monitoring and risk mitigation. Titrate opioids based on responsiveness of patients to initial low doses. Recognize that patients who do not respond to low doses probably will not respond to higher doses. They may be what we can call opioid non-responders. Taper opioids in patients who aren't responding or who are experiencing adverse effects. Have caution when reaching threshold doses. Recognize that there's little incremental benefit with dose escalation but increased harms and that it's much easier to titrate up doses than to titrate down. I'd like you to be aware of two resources offered through PCSS that may be of interest to 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 have the option of requesting a mentor from our mentor directory, or we are happy to compare 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. 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.

opioid therapy

chronic pain

long-term opioid therapy

prescription opioid overdose

misuse

non-cancer pain

opioid prescriptions

risk mitigation strategies