Hello, and welcome to another lecture in the PCSSO Pain Curriculum Training. Today we're going to be talking about opioids for pain treatment in persons with opioid use disorder. This lecture was written by Dr. Patricia Pade, Dr. Sudden Savage, and myself, Dr. Melissa At the conclusion of this activity, participants should be able to, first, identify principles of pain treatment in opioid use disorder, and second, describe pain treatment in opioid use disorder and chronic non-terminal, non-cancer pain. So we're talking about pain treatment in patients who have opioid use disorder. What are some of the goals that we are really going for? Well, I think primarily we're hoping that this treatment will be safe and effective. We do want to support patients' opioid use disorder recovery, essentially avoiding relapse for the use of opioids. And by doing so, we want to initiate and enrich usual recovery activities that are needed to support their recovery. During the course of treatment, we're also hoping to expose them to small rewards that really promote effective pain coping and the maintenance of recovery. And finally, we want to avoid personal and public health consequences of opioid use disorder. As you know, there can be very serious harms associated with this disorder, including opioid overdose, exposure for worsening opioid use disorder in adolescents, as well as other communicable diseases such as HIV, hepatitis C, and other infectious diseases. So we're going to go through the general principles of how to best treat pain in a patient who has opioid use disorder. And the general principles are really going to be about engaging the patient, attempting to treat the pain safely and effectively, addressing the opioid use disorder many times, which will include using medication such as methadone or buprenorphine and counseling, and then addressing the pain facilitators, which may include substance withdrawal. For many other types of pain treatments, it's really important that we're listening and engaging the patient and understanding different parts of how basically the patient's pain expectations and other things. What past experiences can shape treatment choices? What sort of past experience will the patient be bringing, which is going to have them want or expect certain types of treatments? You want to understand their perceptions and expectations of treatment efficacy and how that will impact outcomes. Patients may feel very strongly about certain use of a certain type of medication, such as an IV medication or a particular type of opioid, or may feel that certain medications such as Tylenol are not effective. You want to understand and get investment in the plan and from the patient, if possible, and this really can help facilitate cooperation. You want to plan the treatment when pain is anticipated, so if you know the patient is going to be undergoing a painful surgery or other procedure, you really want to have a plan ahead of time. You want to try to engage the patient in self-management as much as possible, and this is really going to be critical to their chronic pain treatment, as is critical for other patients who suffer from chronic pain who don't have an opioid use disorder, and really this will mean focusing on non-medication modalities or active modalities of treatment. Second, you want to treat the pain safely and effectively. We know that untreated pain may drive opioid use disorder, self-medication, and misuse, so if we attempt to deny that there is any underlying pain, this really can worsen or make their opioid use disorder more severe. We want to reduce or resolve causes of pain when possible. It may not be possible in all cases. It may not be easily identifiable, but if there are identifiable causes, then we do want to address those. We want to provide appropriate pain relief. As you would for any other patient, we're using non-medication approaches when those are effective, safe, and easily available and acceptable to the patient. It may not always be acceptable to the patient, but they should still be offered. Less rewarding medications should be used when this is safe and effective, and we will talk more about that. And then potentially rewarding medications should be used when needed. However, I think putting appropriate limits on their use is important to do, and we'll talk about what less rewarding and more rewarding medications are. Again, you want to plan treatment when pain is anticipated, particularly if a patient is going to have an elective procedure or a surgery, where you can anticipate that there will be a painful event occurring. Next, you want to address pain facilitators. These are commonly some of the different facilitators that can be present for acute pain or anxiety, PTSD, sleep disturbance, substance issues, substance withdrawal. Opioid withdrawal can particularly complicate and worsen acute pain and can cause acute pain itself, so it's very important that you're addressing opioid withdrawal if it's occurring. For chronic non-cancer pain, for patients who have an opioid use disorder or substance use disorder, you're going to want to think about, as well, anxiety, PTSD, sleep disturbance, substance issues, depression, functional losses, learning, and reward as potential facilitators of their pain. And I would encourage you to listen to the other opioid use disorder lectures that we do have in this series for additional information about that. In terminal pain, you may also have many of the same pain facilitators, but you may also be dealing with spiritual challenges, grief over impending loss. All of these things may facilitate and worsen pain or make pain harder to treat. Next, it's very important that you're addressing the opioid use disorder, acknowledging it and understanding that this is going to be a challenge. So acknowledge the challenge, both for yourself and for the patient. Assure the patient that it's not an obstacle to working for analgesia. You can provide analgesic benefit in a patient with opioid use disorder. You want to be encouraging and supportive of the person's recovery. So understand that having pain can be a strong relapse trigger. So as you're doing that, a way that you can do that is to discuss what has been valuable for the patient in the past. Identify or intensify psychosocial supports. Are there counselors who could be available to help support the patient? Does the patient involve themselves in self-help groups such as AA or NA? Does the patient have a sponsor in some of these groups? Different faith-based interventions, mindfulness. We do have a mindfulness lecture that I would encourage you to look at. So really, what sort of supports can you surround the patient with that are really going to help them through a painful period of time? You want to continue or offer pharmacologic support like methadone or buprenorphine for the treatment, particularly if they have an opioid use disorder. But finally, you want to assure safety. So you do need to acknowledge that a patient with an opioid use disorder may not be able to safely take their medication as prescribed. Because of that, you want to be very mindful of how you're prescribing. You want to prescribe a short supply, three to five days at a time, with a lot of monitoring. You want to address any of the physiologic issues of drug use that may be occurring. Again, treating withdrawal as appropriate. If the patient is going through an opioid withdrawal, that can be quite painful, can lead to a lot more anxiety, a lot more sleep disturbances and other things that facilitate pain. You want to anticipate that opioid tolerance will be present in someone who has been using opioids for a period of time, and if that person is opioid dependent, they're more likely to have a higher tolerance to opioids. And be aware that there are rewards, small potentially rewards, that the patient could receive from the prescribed medication. So when we talk about opioid reward, what do we really mean? Well, some drugs and dosing regimens can induce greater reward than others. And this is really a matter of the rapidity of the increase in the blood level of the medication. For instance, an IV medication will have a much more rapid increase in opioid blood levels than an oral opioid. The magnitude of the blood level may be higher in a patient, or in a prescribed IV opioid as opposed to an oral opioid. There can be very specific receptor effects that are occurring from different medications. There's some periodicity of effects, so intermittent versus stable. Regimens such as methadone are very, very stable, have very, very stable effects over time. But some of these rewards do not occur in all individuals, but it's something to be aware of. So this graphic, which is from a previous PCSSO presentation by Dr. Savage, shows how you can have these different effects based on the different routes of administration. So an IV opioid, shown here in red, has a very rapid onset of effect, so that you're getting much greater CNS effects in a much shorter period of time. And at the same time, the analgesic effect is falling much more quickly, and so the pain relief is shorter, and you should expect that pain will recur more quickly. If the medication is given intermuscularly or subcutaneously, there is a slightly shorter onset of action. It does take a little more time for you to get that same reward, sedation, or other CNS side effects. And the analgesic effect appears to be slightly longer, and so it would be more time before the patient has pain again. And in oral administration, you do not have the same increase of effect. You don't get it as quickly as you're getting for the IV or the intermuscular, but you're getting a good response in a short amount of time, and you're actually getting better pain relief overall. So this is an example of why in, say, a hospitalized patient who has the option of having IV, intermuscular, or oral medication, if possible, for better analgesic effect, it actually makes more sense or would be more effective to have longer-acting analgesia. Certainly if the patient is not able to take an oral medicine or something like that, you may need to use these other formulations, but it's important that you understand that these formulations can affect the potential experience the patient is having from the medication. This is a different graph showing this slightly differently, showing you the difference between a PCA or a patient-controlled analgesia, a long-acting or controlled release opioid, and an intermittent bolus administration of, say, a short-acting opioid, oral opioid. And this shows you that the patient-controlled analgesia really is able to keep the patient out of pain and withdrawal, not having as much reward and sedation, and really keeping the patient more in the analgesic area. That being said, you cannot continue PCAs for long periods of time, so this may be helpful right after surgery or in a very acute pain crisis, however, really cannot be continued long-term for patients and can have side effects over time. But the idea that a patient would get a lot of reward or benefit from a PCA may not be as much of a concern as some people may think. And then, as you can see for the long-acting agents, they are working much longer-acting, you're not getting as many CNS side effects, and they have much longer-acting analgesic effect. So there's a lot longer period of time before pain and withdrawal is occurring. The intermittent bolus administration here, shown in red, you can see that the analgesic effects are lasting a shorter period of time, and the patient is having more potential CNS side effects in having, potentially, periods of time where they are having pain and withdrawal occurring again. So considering these opioid reward effects, there are some strategies to minimize if desired. So slower onset medications, such as methadone, can be useful to both treat pain as well as an opioid use disorder. It's important to note that if you're using methadone in the outpatient setting, this can only be dispensed through a federally qualified methadone maintenance program in the outpatient setting. The stable blood levels can be more achieved in sustained release medications, such as longer-acting forms of oxycodone, morphine, and fentanyl, but these may not always be appropriate in patients who are having acute pain or patients in the outpatient setting. You could also consider kappa agonists. These are not as frequently used, but these basically have opioid antagonism at the mu receptor, but they affect the kappa opioid receptor, and by doing so, there appears to be less reward that's associated with them. It's important to note that with these medications, you cannot use opioid agonists, such as morphine, oxycodone, etc. You can think about partial opioid agonists, such as buprenorphine or tramadol, might be more effective. Definitely buprenorphine as a treatment for opioid use disorder. Tramadol may be less rewarding for patients, but can definitely still be abused. These are some of the things you can take into account, but any medication can be misused, particularly opioid medications, if not taken correctly. In acute pain, though, I think you really want to try to focus on relief, and this transient reward that the patient may receive from an IV or intramuscular medication is not going to affect the long-term course of the opioid use disorder, so you're not going to make someone's opioid use disorder worse if they get a few doses of an IV medication. Next, we're going to talk about pain treatments in opioid use disorder and chronic non-terminal non-cancer pain, and we're going to go through a few different cases to illustrate some of the salient features. This is a case of Mr. Smith. He has a pain in his side that won't go away. He's a 35-year-old obese man who is new to your practice. He has chronic, nonspecific, moderately severe right upper quadrant pain. He has a family history of alcohol use disorder. He denies personal history of substance use disorder. He's had multiple emergency department visits for pain and morphine refills, and he's really been troubled by the impact that pain has had on his work. Review of his prior records suggest that he's had extensive workup with no reversible cause for his pain. He has a normal neurologic musculoskeletal and joint exam. He has severe tenderness to palpation in the right upper quadrant. He has an elevated PHQ-9 score, showing you that he has severe depression or likely has severe depression. He's had multiple opioid prescriptions in the past six months from various ED providers, and he's been out, or he reports that he's been out of his extended release morphine for two weeks and would like a prescription today. Part of your evaluation is to perform an opioid risk tool, as we've talked about in other lectures, and based on this risk tool, we're seeing that the patient's risk of opioid misuse is quite high, a 10 on the scale, due to his family history, potential personal history of substance use, which we'll talk about in a minute, his young age, and his depression. You perform some labs and imaging. You do a point-of-care urine drug test, and it shows that he has positive opioids on that test. You identify which opioids, but this is actually an abnormal result, because he's told you that he has been out of the medication or out of any prescribed medication for two weeks, and so you would not expect an opioid positive result here. You perform a CBC, which is normal, a CMP, which is normal, his vitamin D level is mildly low, a vitamin B12 was done, which is normal, and you actually do end up getting a CT scan of his abdomen, with contrast, and that is also negative, so in a patient with the complaints that he's having, what would you do? So the recommendation for Mr. Smith, you express concern about his prior use of extended-release morphine, and you also express concern about ongoing possible use of opioids that he has not disclosed. You explain that the risks of opioid therapy outweigh the benefit at this point, and you do not offer a taper for him, because you're concerned that there could be this underlying opioid use disorder, given the positive urine drug test findings. You would obviously speak with him more about those results, and try to determine more if there is an opioid use disorder going on. You would want to continue the workup to render a specific diagnosis, if possible. In some cases, this may not be possible. You want to offer alternative, safer treatment options for his pain, and refer him for treatment if, during your evaluation, you do suspect that there's an opioid use disorder going on. And you certainly want to follow up with him, and make sure that things are going well. So, when should you say no to a request for long-term opioid therapy? Well, you should say no in patients who have a current, untreated substance use disorder or mental health disorder, because these patients are at extremely high risk of opioid harm. The current recommendations inform us, based on the best evidence that we have, that long-term opioid therapy can actually be more harmful in these cases. So, in cases of, say, a benzodiazepine use, alcohol use disorder, opioid use disorder, or other substance use disorder, you would want to decline a prescription of opioids, particularly for long-term use. You'd want to proceed with caution for patients who are using cannabis, tobacco, or alcohol recreationally. Anyone with a strong family or personal history of substance use disorder, you would really want to proceed with caution. And again, if there's mental illness, trauma, or the patient is quite young, you would want to be very careful about initiating treatment with long-term opioid use. When you do say no to a request for opioids, you want to offer alternative evaluation therapy and continue care. Just because you are refusing to write this particular therapy or provide this particular therapy does not mean that you can't offer other therapies. And you'd want to continue regular patient visits to re-evaluate goals of care and treatment. And it's important that when you're doing this, that you're staying in a risk-benefit framework. So, remember that you're not asking the question, is the patient good or bad, does the patient deserve opioids, should this patient be punished or rewarded, or should I trust the patient? Rather, you're asking, do the benefits of opioid treatment outweigh the untoward effects and risks for this patient or society? So, in that way, you're judging the opioid treatment and not the patient. So, Mr. Smith's outcome, you perform an extensive workup, which ends up being negative. You send him for osteopathic manipulation and evaluation, which is consistent with myofascial pain in the abdomen. During the course of treatment, he admits that he's been making homemade opioid tea from organic poppy seeds, and he's been using that on a daily basis. You talk to him about your concerns for him and your concerns that he has an untreated opioid use disorder, and you re-refer him for treatment and offer him potentially treatment in your office if you have capability to utilize medications such as buprenorphine for the treatment of opioid use disorder. For this particular patient, he declined treatment, and pain remained a problem for him. If he had agreed to opioid use disorder treatment and continued to have pain, what would be your approach at that time? Well, at that time, you would really want to help focus on multimodal treatment modalities because we think that these are the most effective for long-term pain. This would include exercise, meditation, weight loss, complementary and alternative treatments, and cognitive behavioral therapies. You'd want to utilize non-opioid medication options when possible because we feel that these are safer long-term. You may consider opioids for acute flares of pain, but if you were to do this, you would have very close monitoring with informed consent, short prescriptions, and you'd really want to share that risk with a key support person. You'd want to utilize medication-assisted treatment for the partial or full analgesic benefit that it's providing. If we're using methadone for the treatment of opioid use disorder, we can expect that analgesia from this medication will occur for four to six hours after dosing. But remember, again, methadone for the treatment of opioid use disorder can only be prescribed in a federally licensed clinic. Buprenorphine can be prescribed outside of a federally licensed clinic in an outpatient clinic, and this can also provide four to six hours of analgesia. This can be dosed more than once a day. It can be dosed twice a day or three times a day, and this may be effective for pain. You would be potentially using it off-label for pain. If you're using it for both opioid use disorder and pain, this is something to be aware of. And of course, you would need a special DEA X waiver to use it for the treatment of opioid use disorder. What if Mr. Smith wanted to use medicinal cannabis for pain relief? What would you say to him? Well, you would continue to recommend that he get treatment for his opioid use disorder. You would advise him that he's at higher risk to develop a cannabis use disorder given that he has an underlying opioid use disorder. We call this cross addiction. And he is at risk of a cross addiction if he were to use another substance in excess. You would want to inform him about some principles about cannabis, such as its narrow therapeutic window that you can have a lot of side effects very quickly, and it's hard to really dose cannabis. Cannabis with higher cannabidiol content versus THC may be more effective for some forms of pain, but really we do not have rigorous testing at this time to be able to tell us really what clinical outcomes you can see from ongoing cannabis use. It's important to note that cannabis is not regulated by pharmaceutical bodies or anything like that, so the label ingredients may actually be misleading. The label may say that there's high CBD content of cannabis that a person is purchasing, however that has not been actually tested. Side effects of cannabis can include nausea, vomiting, paranoia, worsening of anxiety or depression, weight gain, or reduced functional status. And many of these things would be sort of contradictory in chronic pain treatment, so we would want to utilize medications or modalities of treatment that improve functional status rather than utilizing medications that could potentially reduce functional status. Let's talk about another patient. This is Wendy. She says, help me with my migraines. This is a 43-year-old female with a long history of migraine headaches, high healthcare utilization, depression, anxiety, sexual abuse as a child, and domestic violence as an adult. She sought outpatient treatment for opioid use disorder six months ago but never stopped her prescription for hydrocodone acetaminophen. She's currently maintained on daily hydrocodone acetaminophen twice a day and nortriptyline for her headaches. She continues to have daily debilitating migraines. During the course of your evaluation, she admits that she craves opioids and her functional status is very low. She spends most of her day in bed. She states that she's unable to stop or cut back on her opioids. She's had increased depression, mental instability when she stops opioids. She frequently is obtaining opioids from friends. Her husband is quite concerned about her use. The prescription drug monitoring program that you check for your state shows that she has three dental prescribers, three physician prescribers, and she's been going to greater than four pharmacies to obtain opioids. Does this patient have an opioid use disorder? The answer is yes, she does. But what sounds like a straightforward case of opioid use disorder persisted for greater than one year because subjective and objective measures were not evaluated. And when the prescription drug monitoring data was presented to her, she stated that it was eye-opening for the patient, for her. Her outcome, she was transitioned off of opioids to outpatient buprenorphine naloxone maintenance treatment. Again, to do this type of treatment, you would need special training and a DEA X waiver in order to provide this treatment. She became actively engaged with outpatient opioid use disorder treatment. And in the course of this treatment, her migraines dramatically improved, her hospital and emergency department utilization decreased, her mental health improved, her family life improved, and her quality of life improved. She had a very dramatic improvement in all of her symptoms and health outcomes when her opioid use disorder was treated. If you would like more information about opioid use disorder, we have several lectures within this series that talk more about how you make a diagnosis of an opioid use disorder and how you treat it. So what are some ways that you can address pain and opioid use disorder in your practice? There are some effective models of care. One effective model of care is integrating pain and opioid use disorder clinics in a primary care setting. It could also be in a specialty care setting as well, but most of the research that's been done has been done in primary care. Next are multidisciplinary pain programs can be quite effective. Within these programs, pain and opioid use disorder can be treated. You can maximize active modalities of treatment and enhance self-care. Cleveland Clinic has a great program that's been going on for quite a long time. They've done studies of their health outcomes in this program, and they have shown that in patients who were tapered off of opioids, there was low resumption of prescription opioids at 12 months. So when patients were coming in, they were prescribed opioids. When they started the program, they were tapered off of opioids, and then they followed them up at 12 months. Twenty-two percent of the cohort who were tapered did resume their use, and the single most predictive factor for resuming use was depression. So other things such as opioid use disorder, other disorders were not predictive. However, having depression was predictive. Thinking about integrating pain and opioid use disorder into a primary care clinic, one example of that is Dr. Paid's clinic called the Co-Occurring Disorders Clinic. This is a clinic within ambulatory care that evaluates, treats, manages, and monitors comorbid pain and opioid use disorder. They typically see patients with pain and high risk associated with opioid use, such as history of substance use disorder, family history of substance use disorder, younger age psychiatric illness. It may also be non-compliant or non-adherence patients, patients with complex pain regimens, or patients prescribed high doses of opioids. In this clinic, they integrate the treatment of pain and addiction, and so they really provide treatment for both of those at the same time. They provide pharmacologic and non-pharmacologic treatments for pain in an attempt to minimize opioid use. And this particular clinic is embedded within primary care. Other important parts of this clinic are that providers from this clinic are available for immediate consultation when needed for providers during their primary care sessions. They've seen that there's been greater acceptance of pain and opioid use disorder as a disease like other medical conditions when they have utilized this approach. And in so doing, they've decreased stigmatization within their clinic to really help patients want to seek care for this disorder. And they're utilizing a chronic care model like we would for diabetes or other chronic illnesses to treat the complex intersection of pain and opioid use disorder. Some of their outcomes have been quite impressive. So they have had 65% of the participants who have been seen in their clinic remain active in the program. Many of them have been treated with buprenorphine in the course of their treatment, again, for the treatment of opioid use disorder and pain. 14% have been tapered off of opioids entirely, and 21% have been discontinued. Their outcomes of pain scores have also been statistically significantly decreased. So before coming to the clinic, the mean score, pain score, was 6.39. And then after being in the clinic, the mean score decreased to 5.6. So these scores have decreased during the course of treatment in this clinic, and patients being offered buprenorphine treatment have had a statistically significant improvement in overall pain. And I think you would see similar improvements in quality of life and function. So in summary, treatment of pain in patients who have opioid use disorder, for the treatment of pain, you want to address both the pain and the opioid use disorder and promote its recovery. You want to have attention to the multidimensional experience of pain that patients are having. You want to consider how physiologic dependence and its implications may be affecting pharmacologic management, and you want to choose appropriate pharmacologic management to address this. You want to take measures to support control of medications, as patients may not be able to control their use or be as adherent to these different medication formulations. References are listed here, and I want to bring your attention to the PCSSO Colleague Support Program and LISTSERV, with information listed here, along with some additional information about the PCSSO training. Thank you so much for your attention, and I'll see you next time.

pain treatment

opioid use disorder

safe pain relief

non-medication modalities

case studies

medicinal cannabis

multidisciplinary approach