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Reassessing Tramadol Use in Chronic Pain

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Chronic pain is a prevalent and complex condition where evidence continues to evolve around commonly prescribed therapies. This course discusses the latest systematic review comparing tramadol with placebo in adults with chronic pain, highlighting limited analgesic benefits and the balance of potential harms versus benefits that pharmacists should understand. You will gain evidence-based insights to guide medication review, patient counseling, and clinical decision-making in chronic pain management.

HOST
Rachel Maynard, PharmD
GameChangers Podcast Host and Lead, Clinical & Partnership Education, CEimpact

GUEST
Emma Murter, PharmD, MPH
Clinical Pharmacist, Intermountain Health


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 CPE INFORMATION
Learning Objectives
Upon successful completion of this knowledge-based activity, participants should be able to:
1. Summarize the current evidence on tramadol’s efficacy and safety profile in chronic pain based on placebo-controlled randomized trials.
2. Describe the clinical implications of recent tramadol evidence for pharmacist-led medication management in chronic pain care.

Rachel Maynard and Emma Murter have no relevant financial relationships to disclose.

0.05 CEU/0.5 Hr
UAN: 0107-0000-26-223-H01-P
Initial release date: 6/1/2026
Expiration date: 6/1/2027
Additional CPE details can be found here.

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Welcome And CE Credit Details

SPEAKER_00

Here on Game Changers, we're all about helping you stay ahead of pharmacy practice. But why stop at listening? You can earn CE credit for this episode and hundreds more by visiting CEimpact.com and logging into your account or creating a new one. Get credit, get inspired, and make your learning count.

SPEAKER_01

Hey, CE Impact subscribers. Welcome to the Game Changers Clinical Update Podcast. I'm your host, Rachel Maynard. And today we'll be talking about new evidence that's raising questions about the role of Tramadol for chronic pain. We know chronic pain is common and often difficult to manage, especially given concerns in recent years about the use of opioids. Tramadol is often thought of as a safer opioid option for treating pain, and it's one of the most commonly prescribed opioids in the US. But a recent systematic review and meta-analysis is calling the role of Tramadol for chronic pain into question. So we're going to dig into this evidence and discuss whether it's practice changing and then reassess where Tramadol fits in for managing chronic pain. So to help us get to that bottom line, I'm so pleased to welcome our guest who has special expertise in pain management, Dr. Emma Merter. So welcome, Emma. Hi, Rachel. Thank you so much for having me today on the podcast. We're super excited to have you and thank you so much for taking time out of your busy schedule to be with us. But I know this topic is of interest to a lot of people. So happy to have you and to hear your expertise and to help our listeners learn a little bit more about you. Could you just share a little bit about your background, your current role, and why you're interested in this topic?

Why Tramadol Seems Safer

SPEAKER_01

Absolutely.

SPEAKER_02

So I did a couple of residencies. My first one was at Billings Clinic in Billings, Montana in uh practice management. And then I did a pain management and palliative care residency, PGY2, at the University of Iowa College of Pharmacy in Iowa City. And I am currently the outpatient uh chronic pain management pharmacist at Intermountain Health in Salt Lake City.

SPEAKER_01

Well, that's a perfect fit for this topic, talking about chronic pains. You have a lot of real world experience with this, which is great. All right. Well, excellent. So let's just jump right in. Uh I mentioned that I think people often do think of Tramadol as a safer option and may sort of reach for it when you don't want to go to something like morphine or oxycodone, some of those full opioids. And so is there any truth to that concept about whether Tramadol is a safer option and and and why is it seen that way?

SPEAKER_02

I think probably the first reason it's seen as a safer option is probably prescriber habit, right? It's a controlled three versus a controlled two, which means things like it can have refills on it, and just that lesser schedule means it's it's seen as kind of like more accessible, that that safer option. Clinically, kinetically, you know, tramadol is kind of an interesting medication in that that parent compound tremodol is actually a serotonergic medication. It then undergoes CYP2D6 metabolism and becomes odes methyl tremodol. And that is actually the opioid. So that's actually the opioid component of Tramadol, and that's when you get the opioid activity. So I think that's probably how it was first kind of thought of as safe is you get kind of, you know, first-pass metabolism and all of that, you get like less opioid for the milligram that you're taking. Um, you know, there might be concern for, you know, especially 2D6 being one of the most poly or polymorphism phenotype zip enzymes that we have, you know, how much opioid, how much odis methyl tramadol do you get? Do you get a lot? Do you get a little?

unknown

Right.

SPEAKER_02

That's kind of the question with dramadols.

SPEAKER_01

Yeah, yeah. Yeah. So you highlighted a few things there. It's um, I think the scheduling is a really important concept, and it does definitely contribute to that perception of it being potentially safer. But uh, as you said, it still binds opioid receptors and has opioid activity, but the extent to which that might occur also depends on individual metabolism of the drug based on that um those polymorphisms, as you said. So interesting, interesting concept there to be thinking about. Some people may be getting uh more or less of that opioid effect. Is that right?

SPEAKER_02

Correct. And, you know, when we think about patients who maybe have differing liver function, you know, it's hard to determine in the setting of, you know, hepatitis which enzymes are affected first. But it's typically, you know, CYP2D6 is kind of like our canary in the mind, because it's so many drugs go through CYP2D6. Um, so it can sometimes be that enzyme is our hallmark signature of, hey, there's something going on with metabolism. And with Tramadol going through there, I get really concerned when patients have any sort of liver dysfunction going on and the use of Tramadol in those patients, because if CIP2D6 slows down, we're getting a ton of buildup of serotonergic effects, which has its own concerns and potential benefits. Um but on the other side, if we've got really, really fast CYP2D6, you know, they could be cruising straight through to the opioid, which could potentially lead to opioid toxicity. And the reality is it's so hard to predict. Right, right. In the world of chronic pain, we sometimes call this like dirty pharmacology. And it's not a bad thing, right? Because chronic pain, you know, it's not more acute pain. Chronic pain is maladaptive pain signaling, it's no longer a beneficial danger signal, it's now maladaptive, it's no longer benefiting the patient. Right. And we want dirty pharmacology, we want those receptors to be hit from multiple angles, from multiple pathways. We we want that in an effort to kind of help pain in multiple ways. So tramadol is not the bad thing here. Also, moral assignment of medications is not the role here. But you know, tramadol, where the worry is, is how do we predict safety when the components of it are hard to predict, the percentage, quantity, the quickness. It's challenging to predict in the setting of really standard patients to any sort of dysfunction.

SPEAKER_01

Yeah. Yeah. And I think it's also important to highlight and and reiterate that point you made about um the serotonergic effects of it too, because that, as you said, dirty pharmacology, maybe that's providing some benefit in managing pain theoretically, but also increases risks of interactions and and also with

CYP2D6 Variability And Serotonin Risks

SPEAKER_01

2D6, you know, interactions there. I think so, and I do think many of us probably think of Tramadol as a common drug that we get those interaction alerts with. And a lot of these patients may also be taking SSRIs or SNRIs and at risk for serotonergic effects with all of those. So I think, you know, generally to summarize, it sort of has all the similar risks of opioids in terms of CNS depression risks and sedation and all of those effects, but also the serotonergic concerns come along with that too, because of the mechanism. And so that scheduling doesn't necessarily mean it's it's safer. It may have different also concerns than some other opioids. So where where does it currently fit in? Uh we'll we'll talk about this new study, but where does it where does it historically fit in in terms of managing chronic pain and when would you reach for it?

SPEAKER_02

So I feel like where it fits in currently for chronic pain is again kind of habit. When you have a schedule three substance, sometimes it's nice to be able to put refills on there. It's kind of a more accessible opioid option for a lot of patients because there are a lot of rules around opioid prescribing. Um I feel like where I clinically reach for tramadol is when I have a patient who has neuropathic and opioid responsive components to pain. Again, that dirty pharmacology, that essential like nosyplastic components of pain, where there's some neuropathic elements. I'm focusing on function versus pain. So maybe I'm using Tramadol to help them do physical therapy for a little bit longer to get them to be more functional. But I'm also understanding that there's like neuropathic components that may be like burning, electric shocking. I maybe am not reaching for tramadol if it's just neuropathic, and I'm maybe not reaching for tramadol if it's just gnosyplastic. But if there's like that true functional component that is kind of like opioid responsive, and and I need that like little extra oomph that I would get from like a little opioid response, again, because tramadol is like how much opioid are they getting? So just that like little opioid push to maybe help them improve their function. That's where I'm thinking is Tramadol a potential option.

SPEAKER_01

Okay, that makes sense. Um, and so let's talk about the new recent uh study here. Uh, because I might be something that people have heard about or may come up over time, you know, as people hear many, many patients are on Tramadol. So I, you know, I think it's good to look at the new evidence as it comes out. And so, what can you share about this this research?

SPEAKER_02

Yeah, so this was a really interesting

Where Tramadol Can Still Fit

SPEAKER_02

study. It was done by a Denmark team and they did a pretty substantial meta-analysis. They look at 19 randomized placebo control trials, which ended up having over 6,500 patients. Um, and the cool thing was is that they were able to pull it all down to that uh numerical rating score or the NRS, like a zero to 10, so like 11 point NRS tool, which is really helpful when we're thinking about pain because it's something that we can all as pharmacists pretty quickly evaluate when it comes to like pain. And so they they looked at these 19 studies, and the very impressive thing I thought about this study is they looked at all chronic pain, and they include cancer pain, neuropathic pain, um, somatic disroll. It was the breadth of chronic pain they looked at was was I was impressed by that. Um, I feel like there's oftentimes in pain management studies a lot of exclusions which can make the real world application of some of these medication studies challenging. And so I I was impressed by that. What they found after evaluating the literature was that Tram et all had uh compared to placebo, greater than one point improvement in the NRS compared to placebo. So they had their their conclusions were that had like a moderate or mild to moderate like improvement in pain. But when they looked at side effects, it was like a moderate causing of multiple types of side effects from you know your typical opioid responsive side effects to um mostly the opioid side effects like sedation

Meta-Analysis Results On Pain Relief

SPEAKER_02

and things like that, which for anyone who's ever worked with opioids in chronic pain probably isn't too surprising with either of those results.

SPEAKER_01

Sure. Yeah, yeah, yeah. Yeah.

SPEAKER_02

I think the interesting thing was that they also looked at quality of life. And not all 19 studies looked at the quality of life. They only found five that did so. And they found mostly that it was really hard to report that Tremidol really improved quality of life. And for those of us who work with opioids and chronic pain, we we know this to be true as well. When we use opioids for more than 12 months, there's no evidence that opioids improve quality of life in the setting of chronic pain, which is unfortunate, right? Because chronic pain is not just physically exhausting and hard, it's mentally and emotionally very, very challenging. And so not to digress slightly off of this study, but I think this study highlights that chronic pain cannot be treated with tramadol or medications alone, right? We need multimodal therapy for chronic pain. Uh, we need pain psychology, we need physical therapy, right? We need those other columns of support in chronic pain. But yeah, this was a fantastic study.

SPEAKER_01

And so, in in terms of a bottom line, given the mild limited benefit for pain relief versus the risk of harm, my understanding is that the authors were sort of concluding that tramadol should be reconsider the use of tramadol for chronic pain. If you're already using it for chronic pain, consider the potentially limited benefit against the balance of potential side effects. And they also called out some interesting serious side effects like cardiac events and even cancer events, but questionable about whether there was a direct, you know, theoretical link for why that would be. And I I did find those uh safety considerations uh interesting because why do you think tramadol would be connected to some of those particular risks that they called out?

SPEAKER_02

I suspect that tramadol is probably linked to some of those side effects, not because of the opioid component, but probably because of the serotonergic component. Because again, that tramadol is the serotonergic component and it then has to go through the liver to become Otis methyltramadol. And I think when we think about the risk of opioids, we're often so focused on the respiratory depression and the constipation, and we're not often thinking about what are the other components. Like when we even think about hydrocodone, it's always combined with acetaminophen, right? I have to highlight with all my learners, hey, sometimes it's not even about the opioid toxicity, about it's about acetaminophen toxicity. Sure. Yep, yeah. Um and we have to think about the long-term side effects of opioids as well, right? What are the endocrinopathies? What are the risks to bone or no density? The cancer association, that one I am not entirely sure. I wonder if that was maybe an accidental correlation. Yeah. Um, they did have cancer pain included in the study. Sure. That one I'm not sure if I can entirely link based on the mechanism.

SPEAKER_01

And even the cardiac events, I don't know that there's a clear mechanistic association there, even you know, with tramadol. But interesting again to sort of see, okay, there is this association. We don't know if there's a cause and effect sort of relationship there, but at least that was part of the safety benefit risk balance that they were considering when sort of coming to this bottom line that it should not, Tramadol should not be a first-line option for managing chronic pain. And in terms of whether this evidence is going to change practice, what is what are your thoughts on that? How do you how are you gonna take this information and apply it to your practice? Is it gonna change what you just shared about where you think about the role of Tramadol?

SPEAKER_02

Yeah, so I think I agree and will encourage anyone to not utilize Tramadol as a first-line option because that also is in agreement with what few guidelines we have for pain management. That is an an agreeable statement to that, right? The WHA, excuse me, the WHO pain ladder opioid medications are not the first strong of the pain ladder, right? That's your potential lifestyle management or like your um NSAIDs, acetaminophen, neuropathic pain, right? You're looking at your gabapetenoids, low back pain, NSAIDs, acetominophin, right? You're gonna always choose conservative options. Tramidol should never be a first-line option for pain. Should it be second line, third line? I think this study highlights that there are potential side effects

Side Effects And Quality Of Life

SPEAKER_02

and concerns with Tramadol, whether it's the serotonergic or the opioid component, or really just opioids in general. There are side effects that need to be considered independent of just pain that are probably patient specific. And that's true of a lot of persons with pain. It's you have to take, and I know this is kind of a frustrating component of doing pain management, is you have to take the patient as an individual.

SPEAKER_01

Yeah, absolutely. Absolutely. And uh to just uh emphasize as you I I think you just made a really important point about those non-drug options, those first line options, physical therapy, all of those components. We've obviously seen a lot more emphasis on all of that in in recent years. And so this again just sort of drives that concept home too. I think it's a good opportunity to re-emphasize those first and foremost. But then as you say, individualizing, if you are thinking about going to an opioid, whether it's tramadol or or another opioid, we all of those factors you talked about at the beginning of the podcast are gonna come into that consideration too. The nature of the pain, the patient, their comorbidities or their medications, all of that is gonna be super important in terms of individualizing. And so I guess I guess if you're thinking about if you are at the point of considering an opioid, is it just consider all of those factors? I mean, is there anything else that comes to mind about weighing Tramadol versus another opioid? Or I I mean you've you've very nicely labeled the practical aspects, the neuropathic pain components, the serotonergic medications they might be on, the liver component, you know, any other factors that should we should be thinking about, especially. Yeah, yeah. Yeah.

SPEAKER_02

So, you know, another common medication I like to use in my practice when I get to the point of considering an opioid is buprenorphine, because it also has some opioid receptor. Absolutely. It's a partial antagonist of the muopioid receptor and an antagonist at kappa and delta. Um, but it also has some theorized serotonin activity. So, what's the difference between buprenorphine and tramadol? Well, if I have a patient who has constant pain, I'm probably reaching for something like buprenorphine because it's a long-acting medication. If I have a patient who has frequent pain or maybe has pain surrounding physical therapy, I don't want a long acting, I want a short acting. And so I'm reaching for something like tramadol.

SPEAKER_01

Okay.

SPEAKER_02

Yeah. And, you know, or if you know they're on a ton of other serotonic medications, maybe for concomitant disease states, I'm probably not reaching for either of them. And if I absolutely have to use an opioid, maybe I'm reaching for something like a low dose hydrocodone or a low dose oxycodone or something like that. There is a time and place where you want dirty pharmacology, and there is a time and place where you want clean.

SPEAKER_01

Right. Yeah, yeah. I think that's a great way to think about it. And uh it's unfortunate, you know, it's you want to be able to give black and white sort of recommendations, and it's just, it's just not, it's just not that simple. And it's there's so many factors that come into play there.

SPEAKER_02

I know. I that is one of the reasons I love doing pain management. Um, this is a I tease my other pharmacist I work with. I'm like, no one can tell me what to do because I have to like see the patient as a whole, right? Yeah. I have to kind of like check in with their psychological safety and their home safety. And I have to like check in

Tramadol Versus Buprenorphine Choices

SPEAKER_02

with my community, right? And their community. And I have to see them as a whole person, their emotional, mental, physical state. And I have to take all of that into like into consideration as I come up with a plan for my entire pain management team. And I have a whole team. It is not just me and provider, it is a whole team. And I'm so so thankful for that. Yeah. Um, because it's really important to have that when you're really trying to get after chronic pain. And I'm like, if I had to just follow the ADA guidelines for insulin dosing, I think I'd lose one.

SPEAKER_01

So the gray, you like the gray. I love the gray.

SPEAKER_02

Which makes it hard when I'm trying to give advice to my other pharmacists when they have and you know, even on this podcast too, when I'm trying to give advice for like when and where it's crawl, and it's like you need to look at everything and kind of if the puzzle piece fits, or even if it kind of fits, sure. If there are glaring jagged corners where the tram model just isn't gonna fit, don't do it.

SPEAKER_01

I love that analogy of the puzzle piece. That's a great. Way to think about it because as we we talked about all of those jagged edges and and how they might impact when you're thinking about it or not. And so, does it fit in that puzzle piece of jagged edges potentially fit in with your patient's framework or not? That's just a great analogy to think of my yeah. I love that. So, say you have a patient who's been on Tramadol for some time for chronic pain. How often are you reevaluating that? And how often would you recommend all your colleagues in various settings be looking at those refills, for example? What what are the sort of touch points that you want us to be thinking about and talking with the patients about and reassessing the patient for? What are those follow-ups look like?

SPEAKER_02

That's a really great question. So I would say for those patients that have been on the Tramadol, on Tramadol for, you know, years, months, you know, I would say I'd still want to probably check in with them every six months at minimum, just to make sure that we're encouraging and pairing that with some sort of functional component, right? Are we still using the tramadol to walk the dog, to go to physical therapy, to do the things that actually improve quality of life? For some of my like new start tramadol patients, I like to do monthly and maybe push it out to every three months again to really promote hey, this medication isn't just for you to have pain relief and then like sit on the couch. This is to have pain relief to be have function. I like to tell my patients in the nicest way possible, I don't care about your pain, I care about your function because like I'm not going to cure pain. Medications don't cure pain, right? But medications can help with function. And so what is going to actually really help with function? Physical therapy, psychology, you know, those potentially like interventions, like those things that are actually going to get them moving, get them stronger. And so I use medications to promote those. And if my medications aren't doing that, then I'm asking my patients and myself and the team, what's the point? And I have those challenging conversations, and sometimes they're really, really, really tough to have. And sometimes you have to have them a couple of times.

SPEAKER_01

Yeah.

SPEAKER_02

Yeah. You know, it's ultimately checking in and making sure that you know those medications are still appropriate in that, you

Follow-Ups That Focus On Function

SPEAKER_02

know, are they doing the things that are actually meaningful? Right. And, you know, there was a great study called like the name of the dog. And I love that study because it actually is so, so important. Um, you know, are they doing the things that's important for them? Are they walking their dog? Are they seeing their family? Are they getting on the floor or hanging out with their grandkids? Like those are the things that make our patients who they are, right?

SPEAKER_01

Yeah, I mean, I think that's it's such a really that reminder needs so much emphasis. The fact that these pain medications are not going to necessarily stop your pain. And the goal is to improve your function, improve your quality of life, allow you to do the things that you gave beautiful examples of, walking the dog, hang out with your family, and setting that expectation up front. I'm sure you have to do a really good job of that when it's first being prescribed as well. And then, as you say, early on, having those regular touch points and ensuring that patients are continuing to see those benefits. And if not, especially over time, especially if it's been a while, it's a good opportunity to re-evaluate that and have those discussions ongoing to say, okay, well, if you're not seeing that benefit or being able to go to physical therapy with the assistance of this, then it's not serving its purpose, right? So just such a good reminder. And I think pharmacists in any practice setting can be having those conversations and re-evaluating because often it's it's one of those things I think pharmacists are that's where we're focused is medications. And so we might be the only ones sort of recognizing, oh, this patient's been on this long term. Maybe it's time to check in and reevaluate how it's going.

SPEAKER_02

Absolutely. Absolutely. And this is where I 100% rely on my like community pharmacy colleagues, right? Where I'm like, hey, you might be seeing my patient more than me functionally, like out in the wild, because I do a lot of telehealth. And like, how are they looking? How are they acting?

SPEAKER_01

Yeah, you know, absolutely. Yeah. Well, and again, it's it's it's benefit, but then also the balance of benefits and risks, too, because maybe something has changed in their med profile or their medications or anything else in their life. And you summarized that again so well previously in terms of all those factors to consider, and the balance can change. So, what might have been good a couple months ago may not be good now. So just think it's a very key consideration. And and um yeah, I think keeping all of those things in mind when talking with patients, whether they're a new start or starting it, you know, continuing it for some time, really important factors to be considering. So, Emma, this is great. I thank you so much for your summary of the new evidence, figuring out that it's not really necessarily practice changing, it's sort of what you've already been thinking about for some time, but reinforces that uh consideration of potentially limited benefit given some of those safety considerations, but also individualizing that care is the most important thing, I think, for our patients. And maybe this gives us an opportunity to have some of those conversations. But it is our game changers uh podcast. So we always wrap up with what you think is the game changer that you want our listeners to walk away with. What what would what is the thing that pharmacists can apply today in their practice from from

Game Changer Takeaway And Closing

SPEAKER_01

everything we've talked about?

SPEAKER_02

I think my biggest ask would be if you have a patient sitting in front of you with pain, checking in, treating them with empathy, and you know, really acknowledging that multimodal component to pain management. It's not going to be just medication, certainly probably not just one medication, but you know, that that functional physical therapy potential component of pain really, really is the ticket to chronic pain management, is that multimodal component.

SPEAKER_01

Absolutely. I love that summary. Great bottom line. Thank you, Emma. And again, thank you so much for taking the time to share your expertise. You got a lot of uh practical experience to bring to this. So I learned and I hope our attendees did too, our listeners. Thank you so much for having me, Rachel. Excellent. Thank you. And listeners, we talked about a lot of great practical tips today. These will all be summarized in the practice resource that goes along with this podcast on the CE Impact website. And be sure to claim your CE credit for this episode of Game Changers by logging in at ceimpact.com. And as always, have a great week and keep learning. I can't wait to dig into another game changing topic with you all next week.