Balancing Risks and Benefits When Treating Chronic Pain with Opioids

Lynn Webster, MD, President-elect of the American Academy of Pain Medicine (AAPM) talks about the petition submitted to the FDA by Physicians for Responsible Opioid Prescribing (PROP) and the AAPM response; the current dialogue on the risks and benefits of prescription opioids for managing chronic noncancer pain; and the future of pain management.

How would you characterize the current conversation on the role of opioids in treating chronic non-cancer pain, and how has it shifted in the last few years?

The conversation about the use of opioids for the treatment of pain is much more polarized today than it has been in the past. There seems to be much more noise about the harm associated with opioids than there is discussion about the potential benefits. Nowadays, we always seem to view this as a dichotomous issue, as if it has to be an either/or approach, and I think that’s very unfortunate. There is more middle ground with this issue than just “opioids are good” and “opioids are bad.” There’s some good and there’s some bad, and the challenge is to find the proper balance. Right now, we’re exploring the best ways to safely use opioids for those patients who benefit from them. The other big issue we’re confronting is that so much of the dialogue conflates the two populations that are most affected by opioids: people in pain who are under medical care and people who obtain opioids through diversion who are not under medical care. According to numerous studies, many of the people who are harmed by opioids are people that are not being treated for pain. They could be recreational users or abusers, or addicts, or they could be people in pain or people with mental health conditions who are using opioids to selftreat a combination of issues and comorbidities. When we put all of these patients in the same basket and try to come up with a simplistic approach to solving the problem, a lot of people end up getting harmed.

The non-medical community is increasingly weighing in on the risks and benefits associated with opioid therapy and injecting a lot of emotion into this issue. How much of that is bleeding over into the legitimate scientific debate over opioids?

There isn’t any doubt that this is happening. First of all, let’s be clear: there are tragedies that have occurred from inappropriate (and sometimes even appropriate) use of opioids. These are dangerous medications that, when used by people inappropriately not as prescribed, can lead to tragedy. Whenever unintended deaths or injuries occur, there’s a lot of emotion involved, and I think that’s understandable. However, it takes a lot of strength to understand that there’s a bigger picture that has to be taken into account when these tragedies occur. Don’t misunderstand me, we cannot accept these tragedies. I don’t think that we should say that this is the cost of doing business, or that it is just a consequence of trying to help a larger number of people. That’s unacceptable. But, at the same time, I think that it’s important to try to put it all in perspective so that we can work toward eliminating these tragedies. That includes not only people who are harmed by opioids (including those who have pain and are taking opioids for legitimate reasons, and those who use opioids after they have been diverted), but also the tragedy of untreated pain.

“There could be a large number of people harmed if the FDA and others were to adopt what PROP has recommended. But I think that some of the points that they’re trying to make are valid and need to be addressed.”

-- Lynn Webster, MD

What affect has the PROP petition had on this conversation? By focusing on the risk associated with opioids, and trying to limit access to them, are they doing more harm than good?

I don’t think that the PROP petition has done more harm than good because it has forced a higher level of discussion of this issue. Much of what PROP has said in their petition and what the American Academy of Pain Medicine said in response was already being discussed, but at a lower level. Now these issues are front and center. I think that many of PROP’s positions are flawed, but there are also some important points that PROP presents and the medical community has to accept that they need to be discussed. Opioids have the potential to cause harm, but we need to approach the problem in a scientific way. I think that the PROP recommendations would have large unintended consequences that we don’t want. There could be a large number of people harmed if the FDA and others were to adopt what PROP has recommended.

One of the key things called for in the PROP petition is limiting the maximum dose of opioids to the equivalent of 100 mg of morphine per day. The AAPM and others have called this an arbitrary limit that is not supported by the literature. Do you understand how PROP arrived at that dose limit?

I don’t know how PROP came up with the 100 mg limit. I don’t see any scientific validation for that number. In fact, I find it very difficult to come up with any “appropriate” number that’s not arbitrary. We clearly know that higher doses of opioids are associated with higher risks, but instead of focusing so much on the dose, I think we should focus on what is driving that higher dose. For example, people who have severe pain are likely to require a much larger dose of pain medication than somebody who has moderate pain. We know that people with significant mental health disorders tend to seek higher doses.

Opioids are associated in a general sense with higher risk. But the opioid dose at which an individual is at higher risk depends upon a variety of factors that are unique to that individual what drug they are taking, whether they are using other medications, their BMI, their metabolism, etc. There are many variables that tell me about the patient’s risk that I believe are more important than the dose. Furthermore, it gives a false sense of security to say that you’re safe if you are under 100 mg, or 120, or 180 (or even, as per the APSAAPM guidelines, 200 mg). That is a flawed assumption. As the Academy’s response indicated, one-third of opioid-related deaths are methadone patients, and many of those deaths occur following the first dose of methadone or at much lower doses. I think it is a great error to focus on a particular dose as safe or unsafe. Higher opioid doses are associated with increased risk because of the comorbid conditions associated with the higher doses.

The PROP petition also calls for a 90-day limit on how long patients should be on opioid medications for pain. What would be the practical effect of such a limit?

I think it clearly means that in their view opioids are not to be used for chronic noncancer pain. By definition, imposing a 90-day limit like that means it’s not to be used for non-cancer pain. They’re essentially asking that the FDA not give an indication for chronic non-cancer pain, and I think that that would be a travesty.

That would be a radical departure from current practice.

It’s a very, very radical position. Having said that, it doesn’t mean everyone who has moderate to severe pain is going to benefit from an opioid. Clearly, that’s not true. There are many people who should not receive opioids long-term, who do not benefit from opioids long-term, and who could develop a problem of substance abuse or unintentionally overdose and die. Clearly, that has happened and we need to do more to prevent that from happening. But that doesn’t mean we should eliminate access to opioids for the vast majority of people who tell us the medication has been enormously beneficial to them and that their lives would not be the same without it.

Where does patient autonomy and preference fit into this discussion? How do you reconcile the call for hard dose and duration limits with the multitude of patients who are helped by opioids?

That’s an issue that needs to be reconciled, and I think that’s one of the good attributes that the PROP petition places on the table. It offers us an opportunity to have this discussion. What about the input of people who report that their lives are much improved because of years of being treated with opioids? Should they have a voice in all of this? I think so. That is what has driven me over the years to try to find that balance of safety and benefit. My patients have told me how much better off they’ve been due to opioids. Now, at the same time, I know that some patients have not been honest, and that our struggle is to try to figure out how to manage the risk with the benefit.

-- Lynn Webster, MD

Is that the wildcard in all this? That you still have patients who, despite the educational efforts of their clinicians, take their medications inappropriately, plus the fact that even experienced clinicians can’t be 100% sure that a given patient is not engaging in aberrant behaviors?

I don’t know that there’s any area of medicine that is more complex and more difficult than treating chronic pain patients with moderate to severe pain. It is not just about a neurotransmitter and a receptor. Pain management requires clinicians to integrate a variety of physical sensory and emotional components. And it is very difficult to try to separate all of these things out during a brief interview or evaluation. The other thing to keep in mind is many people who are in pain and misuse their medicines find that the medicine helps them cope in life as well as treat their pain. Most people who have moderate to severe pain have a significant amount of stress. There’s no greater stressor in life than moderate to severe pain, and we know stress increases pain and that opioids may mitigate the anxiety or stress that’s associated with chronic pain. It’s not just the physical component that is being modulated by the opioids; it could also be the emotional component. Separating those out clinically is really difficult. Although it’s dangerous for patients to use opioids more for the emotional component than the physical, it is being done. Figuring out where that balance exists is our clinical, research, ethical, and moral challenge.

Are more pain management clinicians beginning to understand that risk management is really the key to successful treatment with opioids?

Yes. Ten or 15 years ago, we didn’t think opioids had much risk associated with them. Clinicians had a false sense that opioids wouldn’t lead to addiction. Over the last decade, we’ve learned that it’s far more complex than that and that people can misuse and overuse their medicines for many different reasons. Tremendous pain is a horrific experience that people are trying to escape. Some people will do whatever it takes to get out of that horrific experience. Sometimes those actions result in tragedy, whether it’s a person in pain or a person who’s received diverted drug and they’re trying to escape an emotional pain and/or physical pain.

Are primary care physicians equipped to deal with this? Have they received enough training to handle that responsibility?

I think that these physicians are certainly intelligent and compassionate enough. They’re interested in doing the right thing. I don’t think there has been adequate education and training for most physicians, nor is the health care reimbursement structure set up to optimize the care of a chronic pain patient, meaning that there’s usually not enough time allowed to adequately address this. We reimburse far more for procedures and for volume than quality, and that is a perverse structure inherent in our health care system that is contributing to the problem.

Will greater focus on the risks associated with opioids push people more toward interventional pain management?

Oh, I think it clearly will. I think there are a lot of physicians who are afraid to prescribe opioids and don’t have the time to manage patients who are on opioids, or they don’t feel that they have the time because of the reimbursement structure. Interventional procedures are a lot easier. It’s a lot easier to perform an injection than it is to counsel a patient for 45 minutes about why they don’t need a medication. Now, don’t misunderstand me: I’m not saying that interventional pain management is bad. I think pain management is all about taking the appropriate multidisciplinary approach with the appropriate health care reimbursement structure that rewards quality. That’s what we need.

Are primary care doctors prepared to coordinate a multidisciplinary approach to pain management involving other specialists and other modalities? You mentioned that they do not have much financial incentive to do that. Have you seen that changing?

The Patient-Centered Medical Home is an example of how this might work. There are experimental models being tried around the country that attempt to structure care so that the primary care clinician is the hub of everything that is going on. I’m hopeful that we will have such a system in the future for all chronic diseases, including chronic pain. I think that the primary care people have done an excellent job coordinating care for chronic diseases like diabetes, cardiovascular disease, and pulmonary disease. However, when it comes to pain management, they need more training. They receive very little pain management education in medical school and during residency. Frankly, what we really need is a primary residency in pain medicine where all of the specialties can go to get input and direction about the care of people with chronic pain.

-- Lynn Webster, MD

Are there any current continuing education efforts that can address this educational gap in pain management?

Currently, the REMS program for extended release, long-acting opioids has created a large amount of discussion around the topic and has superbly outlined the content of the information that needs to be disseminated. The CDER outline blueprint for the REMS doesn’t talk about research, but it clearly shows where there are gaps in our knowledge and where we need to spend some resources to better understand and advance the field of pain management.

The REMS in and of itself is the discussion point that gives us an opportunity to introduce messages and programs that I believe will have a major impact. I mean, just the PROP petition has created an opportunity to have a discussion at a higher level than we had had in the last decade.

Now that the discussion is progressing, and programs are being put into place, what would you like to see happen next? If you were the czar of pain management in America, what would you like to see happen next? What would be most beneficial for patients and clinicians?

The American Academy of Pain Medicine has developed an educational program that’s based upon eight principles for prescribers. We have to have a consistent message that physicians can understand and adopt that will have an impact. Now, I believe that it is far more complex of a problem than what eight principles can convey. But, at the same time, we have to have something that is digestible, understandable, and implementable that will affect physicians’ behavior. And so the Academy, and work that I’ve done over the last six years, has identified these key educational points that, if they were understood by every prescriber in the country, I’m absolutely convinced would curb a large part of the prescription drug problem, reverse the trend in overdose deaths, and give us time to then have more dialogue about where we go in the future.

Given the stakes that are involved, should physicians be required to participate in educational programs that would lead to that level of understanding?

I think most physicians do not want to cause any harm. Most physicians want to do the right thing. A lot of people volunteered to attend the Safe Opioid Prescribing course at our last annual meeting. We’ve had dialogue with numerous other organizations and interested parties who believe that physicians will seek out this kind of education. I recently gave a full-day course at another meeting and asked the audience whether they would attend a program on how to safely prescribe opioids. They almost all raised their hands. This is topic I believe most physicians want to know more about, and they clearly want to be able to safely prescribe and take care of their patients in pain. I don’t think you have to make it mandatory. I think that doctors and prescribers at all levels will want to do the right thing. All physicians who are prescribing opioids need more education. I think that the standard of care will have an impact on people seeking out that education. As we expand our knowledge about how to safely prescribe opioids, other physicians will want to make sure that they’re able to provide the standard of care.

If there is no real progress made in reducing overdose deaths and injury from prescription opioids in the next several years, do you think there will be more severe steps taken in terms of restrictions on the use of opioids and the scrutiny that physicians are placed under?

There could be. I think this is a crisis. There needs to be a sense of urgency among physicians. We’re the ones in the middle of all of this and are being held accountable or blamed appropriately or inappropriately. We, as physicians, need to feel a sense of urgency to correct the trend and curb the problem, while making sure that our patients receive the treatment they need. I believe that within three years we can have a dramatic impact on reversing the harm from prescription opioids that’s been developing over the last decade. My goal is to work with the FDA, ONDCP, SAMHSA, other professional organizations—anyone who is interested so that we can demonstrate a dramatic reduction in the harm that’s been associated with prescription opioids but also maintain access for those patients who need them. I think we can do that within three years.