Hello, I'm Dr. Steven Pracken. Today I'm going to be talking to you about initiating a trial of opioid therapy. Once you move into pharmacologic treatments, it is helpful to once again consider the type of pain condition you're treating. On the left of the screen, you will see nociceptive pain. As you know, the classics for treatment of this are NSAIDs and things of that nature. Don't forget that duloxetine has indications for nociceptive pain related to back and knee and is worth considering on its own. Tepentadol has a low-level opioid function via metabolite, but is mostly working through its effect on serotonin and norepinephrine. It has minimal addictive potential. Tepentadol has clear opioid receptor function, but at 1 50th that of morphine. The additional effect on norepinephrine makes 50 milligrams as clinically effective as 10 milligrams of oxycodone, but with greatly reduced addictive potential. Both of these are unique and tend to be less problematic than classic opioids relative to misuse. I commonly use them as a half-step up the ladder towards regular opioids, avoiding some degree of risk. On the right, you can see some of the pharmacological options for neuropathic pain. These range from agents such as gavapentin all the way to ketamine. Again, you can see tramadol and tepentadol as midway options. Towards the top of the screen, you again see many of the same agents used for neuropathic pain. In many ways, sensory hypersensitivity, central sensitization, can be considered a special subset of neuropathic pain. Unless the same meds are applicable. Noted here is a caveat that most protocols state that opioids should be avoided in headache or fibromyalgia due to the potential for progression of the disease or other unhelpful outcomes. These are not contraindications or black box warnings. There are many disease states that give rise to pain that opioids are appropriate for and some that are not. Keeping track of this can be difficult. The American Academy of Pain Medicine website shares treatment information for some of the most common disease states that you will likely see in your practice. First, what might contraindications look like? In which patients should you not start opioids? Though this may seem rather concrete from the outside, for those that treat pain, this is rarely a black and white scenario. In a patient with active addiction, starting opioids is obviously a higher risk. But active addiction versus use of illicit substances can itself be at times a gray zone, Most think that finding an illicit drug in the urine drug screen ends the story. But someone using marijuana two times a month or with his high school buddies when he visits once a year is very different than the daily smoker. I'm not suggesting that you treat those that are consistently positive for marijuana. Just that you try to explore what the underlying condition really is before removing them from a potentially beneficial pain treatment that may make them socially functional or employable. Many that use marijuana infrequently are easily able to stop their use once a pain treatment is started and stabilized. Someone with a previous cocaine habit that was positive once last year certainly has higher risk, but may be able to maintain abstinence if their pain is better controlled in collaboration with an MD who is at least curious and not just playing gotcha with the patients. Diversion is an absolute contraindication if it is actually occurring. The most common belief is that diversion is most likely occurring if the urine drug screen is negative for the controlled substance that you happen to be prescribing. The reality is that these atypical urine drug screen findings are commonly explained by other behaviors such as PRN use of the medication, overuse during pain flares, at other times in the month, stopping due to the side effects, or even the desire to stop using the medication as much. Exploring these possibilities can be very enlightening and may even give you clues as to what symptoms need more of your attention. Interestingly, SAMHSA reports that 80% of opioid misuse is for the self-treatment of pain, that's 64% anxiety, sleep, or mood, with the desire to get high only being 10%. Uncontrollable psychiatric disease could be a contraindication if it includes psychosis or active suicidal thought. Once again, these very serious conditions have a spectrum of intensity that may dictate a spectrum of response. There will commonly be partially treated psychiatric comorbidities that just need more aggressive treatment or that may actually improve with pain treatment. The obvious point of this is that even though certain behaviors push us to think of them as absolute contraindications, we would be best served by holding a non-judgmental, more curious approach to patients before making firm and potentially irreversible decisions. These are the cases, however, that may well require input from practitioners in the fields of addiction or psychiatry. We will be discussing this more in Module 3. Now what about an opioid initiation? Remember, we have built up to this moment. We have diagnosed the pain condition, tried to treat it with non-pharmacologic and pharmacologic protocols, but without adequate success. We have sorted out the risk stratification as discussed previously and even have some sense of how to approach this group. Now let's look at some further details of opioid initiation. There are some clinical elements that are universal to all opioid initiations. These are the basic items that need to be clarified or completed before initiating any treatment. As you can see, it is not a small list. It does not have to take an extreme amount of time. The first two items should have already occurred to be in the position to initiate opioids in the first place. We have talked of risk stratification already. As an aside, I always require that I have a UDS result that is consistent with the patient's report before I even start opioids, even if they have been referred and will be out of opioids on the day that I see them. Agreements and consents, which you have heard about, need to be signed. Functional goals need to be clarified so that the patient knows what symptoms and behaviors this trial of opioids is targeting. This trial idea is an important element, so let's discuss it in a bit more depth. Contextualizing any initiation of opioids as a trial is important for setting expectations. The patient needs to be clear that as a treatment, this needs to work with functional goals that need to be met or this trial will be considered a failure and the medication will have to be stopped. Clarity about this from the beginning is central. Opioids are not a treatment for some minor pain control that does not shift function. They hold too many risks for that little effect, and knowing what constitutes success and failure needs to be perfectly clear before starting. Some steps in doing this are as follows. Review the reasons that opioids may help but are imperfect treatments for chronic pain. Review what the patient can realistically expect to do with treatment that he or she cannot do now. Set timelines for the trial that you have to see benefits within identified time, for example, three months. Focus on specific goals for the next visit. Jointly decide how to measure that treatment is actually helping. Offer all prescriptions and changes to those prescriptions as a test of the medication. Setting the goals for the trial is very important. This permits all involved to have a very clear endpoint, thus assisting and keeping a clear cost-benefit analysis about the opioids. This also reinforces the reality that the risk associated with them is high. Keep in mind the goals are pain management, not elimination, and targeted functional improvement. One of the ways of getting clear is using the following mnemonic, which is SMART goals. Look at the specific, measurable, action-oriented, realistic, and time-sensitive goal marks. Let's take a look at how initiating a therapeutic trial of opioid therapy works in practice. Well, Alicia, we've been working on trying to help you with your pain management, with your knee pain, and we're at the point where we're ready to do a therapeutic trial with oxycodone, which you had been on before. Now by therapeutic trial, what I mean is that we're getting ready to start a treatment, and we need to track whether that treatment is helping or not. It's kind of obvious, but it's what we're about. And to do that, we have to have some identifiable goals that we track and see whether the medicine's actually helping you reach those goals. So we usually think of that in terms of pain management, getting your level of pain down, and also improving your function, being able to get back into things that you want to do. So what would be a reasonable goal, do you think, in terms of lowering your pain level? I mean, I'd want my pain to go away. I can understand that, but that might not be entirely realistic for us at this point. So what would be a level of pain that you think, if you were managed at that level, you could get more active and do the things you want to do? Maybe like a 5 out of 10. So decreasing your pain from the 9 or 10 that you usually notice now to more in the 5 range. Okay, that's reasonable. How about function? What are some things that you miss doing that you would like to be able to get back into doing, that if your pain was better managed, you could get back into doing them? Well, you know, I've got a toddler, and so I wish that we could go spend more time together, like go outside. Or I used to take him for like a ride in the stroller, and I can't do that anymore. So I'd really like to be able to walk with him or just take him out. Oh, yeah, no, that sounds wonderful. Yeah, it sounds like it'd be a real win-win for both of you. Yeah. Okay. Well, so if you take him out in a stroller now, how far can you go? Like if you're walking in your neighborhood, how far can you go? Like to the end of the block, and that's it. Really? Okay. So if you take him to the end of the block, you've got to turn around and come back? Mm-hmm. Okay. So what might be a way that we could track whether that's improving? What would you like to be able to do? I mean, I'd like to be able to walk to downtown. Mm-hmm. Okay. All right. So that might be a longer-term goal, that you get to the point where you really can go on long walks. Mm-hmm. But for right now, if you're able to make it to the end of the block, maybe being able to make it halfway around the block before you have to come back? Yeah. And maybe at that point, being able to make it all the way around the block? Yeah. Okay. So that may be some intermediate goals, working towards being able to take longer walks and being more physically active. Mm-hmm. Okay. Well, if you're going to try that, and we're going to track that, how often do you think you want to try and do that? How many times a week would be a good goal? I mean, Henry would love to do every other day. Okay. So we could try that. That's reasonable. Every other day is very reasonable. And how are you going to track it? How are you going to keep track of whether you're doing that and how you're doing? I take a cell phone. Mm-hmm. Just write it down. Put it on the notepad or whatever? Yeah. All right. Great. Well, do that. Okay. Bring it in when you come for your follow-up in a month. We'll see how that's going. And again, our point is we're doing this therapeutic trial to see whether the addition of the oxycodone helps your pain management, improves your function, and if so, it'll make sense to keep prescribing it, right? Okay. Okay. Good. Well, we'll see you then. Hopefully, that role-play scenario helped illustrate how a therapeutic trial of opioids can be initiated. Before we get into starting opioids, I want to spend just a few minutes on the choices we have and what to be aware of. First, there are reasons to use immediate versus extended-release opioids. Immediate-release opioids tend to start faster and thus tend to be more clearly perceived as having an immediate effect. This can be beneficial in terms of a treatment or make it worse for someone with a substance use risk factor. Extended-release will tend to make the response curve flatter and smoother, thus helping with more consistent pain relief, fewer peaks and valleys that could actually promote a euphoric response. But if used alone, could have less benefit for breakthrough pain needs. There are practitioners that will not use immediate-release meds at all, some that rarely use them, and some that use them in combination with extended-release medications for breakthrough pain. For myself, I will use breakthrough pain meds at the same time as extended-release meds if indicated, but try to keep them at a minimum if possible. The next topic is a bit unique and comes from years of clinical experience and repeated conversations with other pain practitioners and addiction specialists. We have recently published an article about this, but in brief, opioids actually stimulate some individuals. I see that oxycodone stimulates about 25% of the patients, morphine about 10%. In general, oxycodone, hydrocodone, and fentanyl appear to have this effect most commonly, though still in a minority of users of opioids. This could be just a curiosity if it did not have associated problems. With mild to moderate stimulation, there may be anxiety or sleep disturbance and a higher chance for sedative prescribing by practitioners, thus complicating the pain management. For some, this is beneficial, helping their energy, their function, their mood. In the latter case, tapering opioids has unexpected negative consequences that need a replacement treatment, or the patient may overuse so as to support their mood or functional needs. In those with high levels of stimulation, sleep disturbance, increased rate of thought, distraction, irritability, somatic agitation, they tend to get opiate-induced hyperalgesia. First-line treatment for this is to rotate opioids if it is causing negative consequences. The stimulation response in an individual is not always to opioids as a whole, but usually particular opioids, so rotation may also be beneficial there. As I've discussed some before, I tend to see tramadol, buprenorphine, and tepentadol as medications that are half-steps on the way from non-opioids to full agonist opioids. Though these agents have opioid function, each has a particular profile that makes them safer and or less addicting. For tramadol, it has minimal opioid function, mostly norepinephrine and serotonin activity. For buprenorphine, it's a partial agonist with a very high safety profile. For tepentadol, it has opioid function, but with norepinephrine function in addition, along with less tendency for withdrawal. The downside is that buprenorphine preparations and tepentadol can be difficult to obtain through insurance. Methadone, though very inexpensive, is the most dangerous of the opioids. It is responsible for a high percentage of opioid deaths within the pain community. The primary issue is that it has a long half-life, surprising people with a high serum concentration following what they thought would be a very reasonable escalating dose. It can also prolong QTC in a small group of individuals. These pharmacokinetics, along with an unpredictable conversion protocol, makes it a drug you need to be very familiar with before using freely. Buprenorphine is a drug FDA approved for the disease of addiction, sublingual in milligram doses, and two preparations for pain, one transdermal and the other buccal patch, all in microgram doses. You can legally use the sublingual off-label for the disease of pain without having a waiver, though it is rarely covered by insurance for this indication. Interestingly, it is the safest of the opioids, primarily because it is a partial agonist. It has a sealing effect that reduces the risk of overdose. It also has a very high binding capacity at the opioid receptor, kicking every other opioid off the receptor. This will even blunt or fully block the effect of other opioids if used concurrently, again potentially increasing the safety profile. Starting a low-risk patient is relatively easy. If basic elements need to be completed, then I suggest that the lower-risk agents be trialed. There can be insurance issues related to these, mostly buprenorphine and tabentadol, but if available it's good to start with these lower-risk agents. These can be surprisingly helpful with greater safety and lower abuse diversion potential, as we have discussed. If they are not effective, then a trial of classic opioids should be considered. They may be used PRN if the patient is manageable with that type of treatment. I tend to start opioids as immediate-release agents if the risk is low, so that I can test the effect of that particular chemical without the concern that a negative effect like nausea, sedation, or stimulation becomes protracted as it would be with a long-acting agent. At times, a very low dose of immediate-release meds used two to three times a day will provide the coverage needed at a lower total daily dose than that available even with an extended-release medication. The use of extended-release meds is a hallmark of chronic pain management. These extended-release preparations are available for every opioid chemical on the market. They're very helpful for chronic, constant pain of moderate to severe level, permitting very consistent blood levels, thus consistent pain control over time. They're particularly helpful for nighttime pain control. They come in many sizes and varieties of delivery systems with a variety of kinetic profiles. Familiarizing yourself with them is important. For medium risk, the basic elements are again completed, and trials of low-risk agents should be considered first. At this risk level, there should start to be a consideration of relative risks for IR versus ER meds. It can be argued that the use of IR meds imparts greater risk of diversion and tendency for addictive behaviors due to a more rapid rate of onset. If the risk level is primarily based on addictive history, then this becomes a more dominant consideration. I will tend to still test chemicals at this level of risk using IR briefly and then depending more on the ER meds for long-term treatment. Collateral information can be remarkably clarifying in high-risk situations. If there is confusion as to mood, function, substance abuse behaviors, then collateral information is very important. At this level of risk, making sure you obtain collateral in the first few months may be all that is needed depending on the level and type of concern. If a substantial part of the risk level is psychiatric disease, then a consult or ongoing collaborative treatment may be appropriate depending on your level of comfort with psychiatric issues. If the risk is present due to substance misuse, then a similar consult or treatment from an addiction medicine specialist could be considered. At this level of risk, there are factors contributing that are not just related to pain. These comorbid issues will need to be focused on and treated aggressively before the pain condition itself can have a positive outcome. For high-risk cases, we once again start with basic elements and trials of low-risk agents. At this level, you may well want to start with low-dose ER medication. Starting with IR meds is not contraindicated. In fact, it is still commonly done and is mostly a stylistic issue. My point is to have you start thinking through each of the decisions regarding medications so that the risk is mitigated. At this point, I think getting collateral information is very important. For many of these cases, depending on the seeming veracity of the patient, I will actually require collateral before starting an opioid treatment. This can happen easily since I will not start opioids without a urine drug screen, thus saying that the second meeting where I discuss the UDS results also requires a collateral source or a trial of opiate will not be considered. If the risk is mostly psychiatric or substance use related, then a mandated evaluation before starting an opioid is also appropriate. Starting an opioid is not contraindicated without this, in particular if you are comfortable with psychiatric or substance-based disease processes. I am just again trying to ensure that it is thought through clearly. As with the medium risk group, focusing on the comorbid issues will optimize for a positive outcome in a pain treatment regardless of the pain modalities used. If you find yourself in a situation where you inherit someone already on opioids, then it is possible to work through the same risk-based treatment with them. Start the same way with the basic elements of initiation. Get all the data, the signatures, educate them about trials, and make a risk assessment. With this inherited opioid patient, you can add an additional way of assessing risk by morphine equivalents. You have to convert all opioids, short and long acting, to a single number representing the total opioid used every 24 hours in morphine equivalents. This represents a dose that can be risk stratified most commonly now by the CDC protocol of less than 50 is low, 50 to 90 is medium, and greater than 90 mL equivalents is high risk. These levels are not universal and actually have weak supporting evidence, but they have come to dominate the conversation on risk and have been adopted by many state medical boards and other individuals. A brief key point here is that when calculating the curve of risk versus mL of morphine, there was no sudden change in the curve at 90 mL of morphine. There's not something unique about that number related to risk. It is essentially an arbitrary cutoff that was needed to provide guidelines. It is important to note, but not to be feared, as an absolute number. Once the risk category is established, then you can return to the previous slide regarding ongoing care and plug this new patient into a treatment protocol and proceed as previously outlined. Thank you all very much for your attention today. I really do hope this has actually been helpful to some degree and look forward to maybe talking again in the future.

opioid therapy

pain management

pharmacologic treatments

addiction

substance use history

trial