Bret S. Stetka, MD | Disclosures
Introduction
Last week, while speaking at the National Rx Drug Abuse & Heroin Summit in Atlanta, National Institutes of Health Director Francis Collins announced a plan to help improve pain management in the United States. Specifically, he hopes to expedite research into safe, effective pain medications to help address the opioid abuse epidemic now blanketing the country. As many clinicians now know, the numbers are shocking: On average, prescription opioid analgesic and heroin overdoses kill nearly 100 Americans a day. "Our list of options is woefully short," said Collins.
There are signs that at least in some cities, counties, and states, things may be improving, as health care providers, patients and policymakers take steps to address opioid abuse and misuse. Stricter prescribing laws have been enacted. Doctors appear to be overall prescribing fewer opioids. Yet the role of opioid-based pain management is as contentious a topic as ever, and curtailing opioid prescribing brings with it new clinical questions—including what treatments to turn to instead, and how to prevent some patients from seeking out alternative, more dangerous opiates, such as heroin.
Roger Chou, MD is a professor of medicine at Oregon Health & Science University who studies pain management and how to address opioid misuse. Last year, he served as one of the lead authors on the Centers for Disease Control and Prevention (CDC) guideline[1] on chronic pain; he also has served as director of the clinical guidelines program for the American Pain Society. In addition, Dr Chou is involved in collaborative initiatives with the American Academy of Addiction Psychiatry (AAAP) that are designed to educate clinicians on safe and effective pain management; one such initiative is the Providers' Clinical Support System for Opioid Therapies (PCSS-O), funded by the Substance Abuse and Mental Health Services Administration.
Medscape recently spoke with Dr Chou about his efforts to help address the opioid epidemic, and what role these medications should play in chronic pain management.
Medscape: Hello, Dr Chou. Let's get right into it: Do you personally feel opioids have a role in chronic pain management?
Dr Chou: Yes, I do. But I think the role should be more limited than it has been in the past. I don't think we have a great understanding of the limitations of opioids in terms of effects on pain and improvement in function, and we know a lot more now about the serious harms associated with them, including overdose, addiction, and death. People vary in their response to opioids, as well as in what kind of side effects or risks they experience. There's a lot of individualized decision-making that needs to occur.
I think that lower doses of opioids may be appropriate in selected patients. We do need to be more cautious about who we prescribe opioids to. And we need to be better about how we monitor and manage them, and how we mitigate their risks. This includes being sure that we're doing regular urine drug screens and using information from our prescription data monitoring program, giving people such things as naloxone, avoiding high doses, avoiding benzodiazepines—all of the things that we talk about in the CDC guideline, as well as in the PCSS-O materials.
Opioids are what I would consider an adjunctive treatment. Everything we know about pain is that this is a complex biopsychosocial phenomenon, and that we need to address the psychosocial contributors to pain.
Opioids are what I would consider an adjunctive treatment. Everything we know about pain is that this is a complex biopsychosocial phenomenon, and that we need to address the psychosocial contributors to pain. One of our big goals should be to get people more functional. Unfortunately, giving somebody a pill doesn't do this the vast majority of the time.
We need to be using active treatments. These are typically nonpharmacologic therapies, such as exercise therapy, cognitive behavioral therapy, some mind/body interventions—interdisciplinary rehab that actively engages patient in their care, by focusing on coping strategies, movement, and improvement in function. Then, if we need to, we may consider opioids as an adjunct. Again, not everybody is appropriate for opioids, and we do need to be more selective about how we use them.
Medscape: Do you think opioids can ever be a long-term solution for patients?
Dr Chou: Ideally, we would eventually get most patients off of them. However, in reality, the properties of opioids—the fact that people get physically dependent and develop a tolerance on them—make it very difficult. The data do tell us that somebody who's been on opioids for more than 6 months or 1 year are likely to be on them for many years.[2,3] It's difficult to get patients off of opioids. We need to be very careful about how we use these. I don't think there's anything inherently wrong with maintaining somebody on low doses of opioids, as long as it's doing what it's supposed to in terms of helping their pain and function and not causing harm. But yes, ideally we could taper people off once we help them understand coping strategies—and once other factors that contribute to pain are managed, such as depression and sleep problems.
There are some pain doctors who are very aggressive about tapering opioids and using nonpharmacologic and nonopioid therapies, which are actually quite successful. But for many primary care docs, this is still a big challenge. But we're trying to get there, trying to understand how to use these nonopioid therapies better.
A big part of this, of course, is getting better access to all of these treatments. It can be very difficult in many places, including my own, to access adequate psychological care and interdisciplinary rehab. All of these things that we think are good alternatives can be difficult to access and get reimbursed for. There are a lot of challenges there.
We are starting to make some progress. We've started to see some of the overdose data and prescribing rates shift down. On the other hand, we have seen a bump in the use of illicit opioids, which we think is related in part to people who develop opioid use disorder for prescription opioids. So there's multiple things going on simultaneously. It's a matter of addressing both sides of this. We have to deal with chronic pain better, including how we use opioids, and we also have to be better at identifying opioid use disorder and in treating and managing it.
Guidelines, Policies, Contentions
Medscape: Tell us a bit about your work over the years in pain management research and policy. To what extent are prescribing guidelines still being debated?
Dr Chou: Back in 2009, my colleagues and I formed a panel with the American Pain Society to produce one of the first national guidelines on the use of opioids for chronic pain.[4] We were one of the first groups to say, "Maybe you shouldn't use the highest dose and keep increasing the dose indefinitely. Maybe there should be some dose thresholds." People got really angry about that. There weren't a whole lot of data back then, but there was some support behind what we were doing. There was no randomized controlled trial that used doses greater than 160 or 180 mg of morphine equivalents per day, but there were patients who were getting 500 mg, even 1000 mg. That was not that unusual 5-10 years ago.
Around the same time, the Washington State Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain guidelines were released.[5] They emphasized the dose issues as well, and there was a lot of resistance.
I can't think of any other drug—in my lifetime, at least—that has caused these kinds of issues. It's become a major public health concern.
Over the years, we've seen more and more data come out about the epidemic of overdoses. I can't think of any other drug—in my lifetime, at least—that has caused these kinds of issues. It's become a major public health concern. Even with the CDC guidelines, there was some controversy and a lot of discussion about what the guidelines should say, but really I think that there's a big need for it.
My impression is that there are some challenges in implementing the guideline. Some people, groups, or jurisdictions are being very aggressive about some of the dosing parameters. The guideline does not say that everybody needs to be tapered below 90 or 50 mg of morphine, but some groups are interpreting it that way. There are some challenges in implementation, but I think the general approach toward the use of opioids has definitely shifted over the past 5 or 10 years.
I am on the steering committee for 2 initiatives in collaboration with the AAAP, which will soon be combined which we're hoping can help clinicians with all of these questions – questions around when and how to prescribe opioids, and how to treat patients who have become addicted to them.
The PCSS-O project helps clinicians increase their confidence around prescribing opioids, whereas its counterpart, the Providers' Clinical Support System for Medication Assisted Treatment (PCSS-MAT), provides education and resources on the evaluation and treatment of opioid use disorder, including use of medication-assisted treatment, such as with naloxone. We now have a very large compendium of over 100 expert webinars to help doctors and clinicians use opioids properly and to treat misuse and abuse.
Origins of an Epidemic
Medscape: What factors do you feel have most contributed to widespread opioid misuse and abuse?
Dr Chou: There have been a lot of factors. There was a perception that pain was being undertreated and that we weren't utilizing our most effective analgesic (opioids). There were actually movements in a number of states to be permissive to use opioids for this purpose, which previously had been discouraged or considered contraindicated. You could basically only use opioids for acute pain or cancer pain back then. Several states rewrote their regulations to say you can use opioids to manage chronic pain in people who aren't dying. There was a much bigger emphasis on treatment of chronic pain, including calling pain the "fifth vital sign."
Some studies were published that suggested low rates of abuse or addiction for people with chronic pain prescribed opioids. The data are actually really flimsy and mostly observational. One of the studies that's very commonly cited is actually just a letter to the editor by Porter and Jick[6] that appeared in the New England Journal of Medicine in 1980 andis literally less than 100 words long. It reported a low rate of adverse events among inpatients and was not really applicable to long-term chronic pain. A lot of people took that to say that the rates of addiction and problems with opioids are actually very low. It's been cited extensively.
There was also a lot borrowed from the palliative care world, including the idea that there is no dose ceiling—that you keep titrating up the dose until somebody either has pain relief or has intolerable side effects, but we know that you cannot achieve total pain relief in the vast majority of patients in clinical practice. The average pain relief with opioids is somewhere around 1-2 points on a 10-point pain scale vs placebo. Few people have their pain completely relieved. There is this perception that opioids are much more effective than they actually are, in part because we didn't have a great understanding of chronic pain and how it differs from acute pain.
There are other factors, including the introduction and very aggressive marketing of long-acting opioids. Long-acting, sustained-release oxycodone had an unprecedented marketing push behind it, and for a while was one of the top-selling drugs of many state formularies. The perception was that somehow these long-acting, sustained-release formulations were safer or more effective opioids, none of which has ever been proven.
There was also a shift toward patient satisfaction—with physicians being worried about how they were being rated, and with some of their pay being dependent on how patients scored them. That sort of thing.
The bottom line is that this happened in the face of very little evidence regarding either safety or benefits. We were really flying pretty blind, and unfortunately, it took 10 or 15 years before people really started noticing some of the issues.
Deterring Abuse: What Works
Medscape: There have been several efforts to deter abuse. How effective have such things as prescription monitoring programs and abuse-deterrent formulations been?
Dr Chou: The prescription monitoring programs have certainly helped a great deal. And the abuse-deterrent formulations probably have some beneficial effects. It's very hard to study; nobody's been able to show that using abuse-deterrent formulations has reduced the risk for, say, overdoses. But just on the basis of their physical properties or how they're formulated, they seem to make sense.
To me at least, one of the big issues with the abuse-deterrent formulations is that they're really meant to prevent somewhat extreme forms of abuse (ie, crushing the pills and snorting or injecting them). Most overdoses are probably not occurring that way.
If somebody's not safe to use opioids, you can't give them an abuse-deterrent formulation and think that they're going to be safe, right?
There are definitely some people that do that, but most people think that the majority of overdoses are from people just taking too much of the pill. The abuse-deterrent formulations aren't going to do anything for that, so I think it's easy to fall into this false sense of security that they'll somehow make things safer. It will help to some degree, but I don't think it replaces clinical judgment and all this other stuff we were talking about. If somebody's not safe to use opioids, you can't give them an abuse-deterrent formulation and think that they're going to be safe, right?
Medscape: What about removing acetaminophen from the combination treatments? Could this have a measurable effect?
Dr Chou: There were concerns about acetaminophen overdose, some of which has to do with individual variability and susceptibility to liver toxicity from acetaminophen. Even at 4 g, which was previously the upper recommended dose per day, some people experienced liver toxicity, and some people can experience it at doses lower than that. The US Food and Drug Administration has changed some of its guidance about the maximum dose.
The other issue, of course, is that some people inadvertently overdose because they didn't realize that acetaminophen was in there, which is an issue if you're taking 16 pills instead of eight, combining it with other over-the-counter medications.
Most of the prescription opioid overdoses—at least from the data I've seen—are separated out from the acetaminophen toxicity. There's a big difference in how these things present. Dying of liver failure from acetaminophen is a slow, agonizing process that occurs over days, whereas if you overdose on an opioid, you stop breathing and it happens right away. You code it differently, and it's looked at differently.
Acetaminophen has some impact in terms of the liver's side of things, but I don't think it's had a major impact on most of those overdose deaths that we're talking about, which are related to respiratory depression. I will say, though, that the issue of combining benzodiazepines and opioids is one thing that the CDC guideline emphasizes quite a bit. It doesn't seem to have received a lot of attention before the past 5 or 6 years, but all the data suggest that combining benzodiazepines and opioids really increases the overdose risk. There's some additive or synergistic respiratory depressant effect. We're trying to get people away from that.
Naloxone: Promises, Challenges, Friends, and Family
Dr Chou: Naloxone is something else we're trying to understand. It's traditionally been used in injection drug use settings, essentially in people using illicit drugs. In theory, it could prevent overdoses from prescription opioids as well. It's quite underutilized.
There are some big issues surrounding the pricing of naloxone. The autoinjector price jumped up from $600 to $5000 per injector over the course of around 6 months. The nasal spray form approved by the US Food and Drug Administration is also quite expensive. So there are some definite pricing issues there. You can jury-rig an intranasal delivery system that is cheaper, and people have gone off-label to deliver and prescribe it.
That being said, we think that people having access to naloxone and being aware of how to use is important. It's really meant to be administered by family, friends, and bystanders who witness an overdose event, and really does have the potential to prevent fatal overdoses.
Medscape: To your knowledge, how widely is naloxone being prescribed these days with prescription opioids?
Dr Chou: It's not. I haven't seen a lot of data yet, but that's my feeling, based on my conversations with other clinicians and even in my own practice. It's something I've tried to be a lot more conscious about in the past 6 months or year. Many people who have an overdose episode are put right back on the same dose of their opioid. My guess is that very few, if any, of them got naloxone and probably should have.
Many people who have an overdose episode are put right back on the same dose of their opioid. My guess is that very few, if any, of them got naloxone and probably should have.
Again, cost is still a problem, but many insurers are now paying for it and many health departments are trying to make it available as well. It's starting to become more widely used. I found it can be a useful tool to talk to patients. I'll tell them, "I want to prescribe you this medication, because if you overdose by accident, I want there to be a way for somebody to reverse that episode." That can really be a wake-up call to patients, which makes them realize it's serious enough that I want to give them something. I've found that to be pretty helpful in terms of educating people about risks.
Medscape: Do you bring the patient's family into these discussion?
Dr Chou: It can be very helpful, yes. Of course, there are issues with patient confidentiality. You have to have permission from the patient to talk to folks, but I haven't had that be a major issue most of the time. Usually, I'll know their primary partner or caregiver. They may come with the patients to the visits, or I'll ask the patient for permission to talk to them on the phone. Where I practice (Multnomah County, Oregon), there are a lot of educational materials about opioid overdose and giving naloxone. I can print that out and give it to the patient so that they have it and can recognize signs of overdose.
The other unique thing about opioids, of course, is that they pose a risk to not only the patient, but also other people in the household, including kids and family members. People have this perception that prescription pills are safer than street drugs, so they'll take them from the medicine cabinet and experiment with them. We try to do education about securely storing the pills, using a locked box, that kind of thing.
Properly disposing of the medications is another big issue. It is not easy to get rid of these pills. I had my wisdom tooth taken out and somebody gave me around 40 pills of oxycodone, when I probably needed 2! That's a lot of leftover oxycodone pills. We're trying to work on that side of things as well.
Marijuana: An Ounce of Prevention?
Medscape: You mentioned street drugs. A recent study in JAMA reported that in states that had legalized medicinal marijuana, the opioid overdose rate has fallen 25%.[7] Do you have any thoughts on whether legalization of marijuana—at least medically—is perhaps another way to deal with this?
Dr Chou: Some of those data are epidemiologic, of course, so they're a little hard to interpret. I think we need more research to understand what's going on. We don't have a lot of evidence, in part because there's not a lot of federal funding, at least not at this point, to do marijuana research.
I would say that there isn't consensus among experts about how to approach marijuana and opioids in chronic pain. There's actually very little data that marijuana directly affects pain. What it does do is make people feel relaxed and good, and they may forget about their pain for a little while. Whether it helps to improve their function is another question, and there are other issues with the marijuana.
Marijuana is a very complex substance, it's not a single drug. There's the cannabidiol (CBD) component, which is what we think is the medicinal component is, vs the tetrahydrocannabinol, or THC, which is what causes the psychogenic effects. There's very little standardization or quality control. Even if somebody tells you that what you're getting is high CBD content, you have very little confidence about what the actual percentage is.
I live in a state where marijuana is legal not just for medical purposes, but also recreationally, and many people use it. I certainly have patients who will tell me they are using marijuana, and I will spend some time educating them about the differences, the content of the marijuana, and the risks of smoking it. I assess them to see whether they've got cannabis use disorder, because if they do, that's a flag that they are at risk for opioid use disorder as well. I don't want them using both if that's the case.
If people are using marijuana in a way that's occasional, doesn't seem to be problematic in terms of pain management, and helps them to decrease their opioid use a little bit, I'm okay with that. There are some people who aren't, so again, I don't think there's complete consensus on this yet.
As marijuana becomes legal in more and more states, we're going to continue to deal with this. I will say that marijuana doesn't cause overdoses. Alcohol and opioids are probably more dangerous if you're talking about overdose risk. Some would say that nicotine is more addicting than marijuana. We discourage alcohol use with opioids of course, but it's highly likely that a lot of patients drink a beer or two, and many docs either don't know about it or don't make a big deal about it.
Personally, I'm not sure that I would prescribe marijuana for pain myself. The clear medical indications for cannabis are relatively limited: HIV weight gain, some of the hyperemesis conditions, and things like that. But again, if somebody came to me with chronic pain and said, "I'm really worried about using opioids, and I'd prefer not to," I would probably say if you can control your use of it, still engage in and do the other things we should be doing to help you manage your pain (eg, exercise therapy, physical therapy if indicated), and manage your depression and all this other stuff, I would probably say it's okay for them to give that a try. But this is all based on individual experience at this point.
Parting Thoughts
Medscape: Do you have any final thoughts on where we're at with this opioid problem?
Dr Chou: The world has changed in terms of how we're using these opioids. As I said, it's going to be a challenge moving forward, but I think we're already making progress.
My last comment is just that it's relatively easy for us not to start opioids in the first place or not titrate people up to really high doses. What's a lot more challenging, and I think what a lot of people are dealing with right now, is what to do with those patients who are already on very high doses and are having difficulty tapering down. This is going to be an ongoing conundrum that we're going to be dealing with for the foreseeable future. That's a challenge we acknowledge, and for which we are trying to develop approaches and tools to help manage those patients. But, it's not going to be simple or easy.
Published in association with the American Association of Addiction Psychiatry.
Dr Chou has disclosed no relevant financial relationships.
