This drug could make a huge dent in heroin addiction. So why isn’t it used more?

November 23, 2013

Much of my public-health research has concerned measures to reduce the social and health harms related to the misuse of heroin, prescription painkillers, and related drugs.


(BRIAN STAUFFER FOR THE WASHINGTON POST)

Opiate misuse is a huge problem. In 2010, more than 19,000 Americans died from opiate overdose. By comparison, about 11,000 Americans died from gun homicide. Over the past 35 years, about 200,000 injection-drug users have died of HIV/AIDS.

Substitution therapies — first methadone, more recently, buprenorphine — provide an imperfect but essential tool to treat opiate disorders, and thus to ameliorate harms associated with the misuse of these substances. Our research group has published many studies trying to understand how outpatient treatment facilities can provide these therapies most effectively. This is a major challenge and opportunity in the Affordable Care Act, which greatly expands access to substance abuse treatment services.

This week, the New York Times’ Deborah Sontag published an extensive two-part series, “Addiction treatment with a dark side,” on buprenorphine misuse. The piece is vividly written. It shows the human faces of many drug users. She frankly depicts underground market in buprenorphine, and describes unethical providers who have profited from this medication.

Like many addiction researchers, I’m uneasy about this Times piece. The specific facts are well-researched. There’s some beautiful reporting, such as Sontag’s discussion of the liberating effects of receiving medications at a regular doctor’s office rather than at a forbidding and inconvenient methadone clinic.

Yet the very vividness of the human portraits leaves readers with powerful impressions, and misimpressions. One puts down these two pieces with powerful anecdotes reinforcing the view that buprenorphine is more widely abused than it actually is, that buprenorphine is more dangerous than it generally is, and that buprenorphine providers are less ethical than they generally are.

Sontag cites a statistic that buprenorphine was involved on the order of 42 deaths per year over the past decade, with other substances likely playing the most active causal role in most of these cases. That’s a frightening thing, but it matters that these occur in a population that now experiences 19,000 overdose deaths every year.

A quarter-century ago, methadone treatment was deeply stigmatized among patients, providers, and the general public. Prominent critics included Charles Rangel, Rudolph Guliani, and even Howard Dean. Opposition to methadone—reflected in under-funding, Not In My Backyard (NIMBY) problems, and low take-up among patients who would benefit--caused needless suffering, particularly when barriers to treatment coincided with the worst days of the HIV/AIDS epidemic. These controversies distracted attention from practical ways methadone treatment could be improved. I and many others worry that buprenorphine might acquire some of the same stigma.

To discuss these issues, I interviewed one of the nation’s leading buprenorphine experts, Brown University’s Peter Friedmann. Dr. Friedmann is a general internist, an addiction medicine physician and services researcher. He’s been treating buprenorphine patients since 2003. Past president of the Association for Medical Education and Research in Substance Abuse (AMERSA), Friedmann is a fellow of the American Society of Addiction Medicine and the internal medicine specialty director on the American Board of Addiction Medicine (ABAM). I should mention that we are colleagues on two ongoing studies.

Below is an edited transcript of our conversation. Many readers have never heard of buprenorphine. So this interview is a little longer than usual, with more background and shop-talk. The internet is a glorious place for longer-form interviews….

Harold Pollack: Let’s start with the basics. What is buprenorphine?

Peter Friedmann: When you split open the poppy, which is where most natural opioids come from, you find many psychoactive products. Morphine is the most well-known. This is what's processed and made into heroin. One of the other products present within the poppy is thebaine, which is processed into buprenorphine.

The term opioid refers to compounds that are active at the mu-opiate receptor. The term opiates refers only to naturally occurring forms.  Buprenorphine happens to be one of the innumerable classes of natural, synthetic, and semisynthetic compounds that work at that receptor. That receptor is responsible for many of the effects we see of opioids in our society. These include pain-relieving effects, relief of suffering, but also the euphoria and some of the problems we see with them.

HP: Buprenorphine provides a “substitution therapy” for people with opiate disorders.

PF: Correct. For many years, opiate addiction was considered an incurable illness. It was Dole and Nyswander in New York who proposed that we might stabilize the social and physiologic effects of opiate addiction by administering a long-acting oral, preferably an oral agent, for substitution therapy. The first widely-used medication was methadone, which is a full opioid agonist. Buprenorphine, a partial agonist, has been around for a long time. It's been recognized as a potential treatment for the last several decades. The Drug Abuse Treatment Act of 2000 opened things up for its use in opiate addiction treatment.

HP: Can you explain what an “agonist” is?

PF: An agonist is something that occupies and activates the mu-opiate receptor. Medications that operate on this receptor include full agonists, partial agonists, and antagonists. An antagonist is a blocker, so it occupies your opiate receptor, but does not activate it – so your receptor is blocked but you don’t get any pain-relief or euphoria. Antagonist medications include things like naltrexone and naloxone. These are helpful in a variety of situations. But there’s a problem with these medications in maintenance therapy. Because you don't get any agonist effect, it’s not enforcing for people to take it.

HP: These have value in treatment and in overdose prevention. But it’s unpleasant for people to take these medications. So there’s poor adherence to these in addiction treatment.

PF: Yes, for an opiate user, these don’t relieve a lot of craving. In terms of adherence to treatment, there's nothing in these antagonists that's re-enforcing for many patients.

In contrast to that, buprenorphine is a partial agonist, which means it will occupy but only activate the receptor up to a certain point. Because of that, it's thought to be safer than a full agonist such as methadone, which has greater effects on respiratory depression, euphoric effects, and so on.

HP: So you're less likely to get high on bup, and you're less likely to have depressed respiratory function and other associated effects of opiates that can be life-threatening.

PF: Yes.  Bup can be taken under the tongue, and it's absorbed fairly well. It doesn't have to be injected, which is obviously a critical public health concern. It has a very, very long half-life. It sticks around for a very long time, means that people can be treated with dosing once a day or sometimes three times a week.  And it binds strongly to the mu receptor, so it prevents heroin and other full agonists from working, effectively extinguishing the drug use behavior.

HP: Many people would say that maintenance therapies such as buprenorphine or methadone simply substitute one addiction for another. Why is that beneficial for that person or for the society?

PF: This gets to the definition of the term “addiction.” One might claim that you're substituting one addiction from another, but you're not. Maintenance therapy doesn't have the same compulsive quality. It's not as re-enforcing as short-acting opiate such as heroin. By occupying the receptor with a long-acting agent, we reduce many of the most concerning and harmful compulsive behaviors that go with opiate addiction.

HP: You said that buprenorphine is generally safer than methadone because it's only a partial agonist. What are some things that distinguish buprenorphine from methadone in your clinical life that might make one of these more appropriate than another for particular patient?

PF: Most of the differences reflect differences in the treatment system through which we administer these drugs. By federal law, methadone must be delivered in a highly-structured opiate addiction program. It cannot be delivered in a physician's office. Buprenorphine can be.  The Drug Abuse Treatment Act of 2000 was revolutionary in its specific intention to allow physicians who meet certain criteria to administer it in their office.

Patient severity also tends to differ. In general DATA2000 was intended to reach many people who perhaps have had less severe opiate dependence, or who were unwilling or unable to access a methadone program.

HP: I should note that maybe 20 percent of the people with some level of opiate disorder or misuse will ever access the specialty addiction system. If you can provide services in a physician's office, you can reach a large number of people whose needs wouldn't be otherwise be addressed. Are there other patients for whom methadone is the preferred treatment?

PF: If you're delivering patient-centered care, you're trying to meet the patient's preferences. I think the vast majority of patients would prefer sort of the office based setting to the highly-structured methadone setting. That said, when people have severe addiction, psychiatric, or medical problems, it’s often preferable that they'd be seen in the highly-structured environment of a methadone program.

Also, there's also no dose limit on methadone. So you can keep raising the dose until you’re able to reach a blocking dose for people with severe addictions. Methadone also has a mandatory counseling component; whereas in buprenorphine practice you must have the counseling available but it's not mandated. So for people who have complex problems, methadone is sometimes preferred.

Addiction treatment with a dark side

HP: Now, let's move to Deborah Sontag’s New York Times article, 'Addiction Treatment With a Dark Side'. This has gotten a lot of attention and has upset many people in the treatment community. It's a pretty scary piece. It profiles several people who have overdosed on Suboxone (the form in which buprenorphine is sold).

PF: I was concerned about this piece, for a few reasons. First of all, the field of addiction medicine is very stigmatized. In terms of wanting to bring good practitioners into the field and also trying to gain public and political support for these valuable and highly effective treatments, I think it was quite harmful.

HP: Since its inception, methadone has been extremely stigmatized in the minds of the public, many patients, and providers. Articles such as this one raise the possibility that a similar stigma might be recreated for buprenorphine.

PF: Right. Sontag included many anecdotes that were given equivalent weight to the enormous amount of data and clinical experience out there showing that buprenorphine is a life-saving therapy.

There were other things, too. Bad providers clearly exist, as they exist in all of medicine. Sontag writes that doctors who provide buprenorphine are more likely than the general medical profession to have some history of disciplinary action against them.

This is a tough issue, which reflects how stigmatized the addiction field really is. Some people who go into the addiction field have had addiction themselves. So they've been disciplined on that basis. People rarely come out of medical school saying, "I want to be an addiction doctor."

Because the addiction field is accepting of recovery, many doctors in recovery gravitate there. Suppose, for example, you’re an anesthesiologist, and you have problems with fentanyl. You get censured and you can't practice anesthesia so you look for an area of medicine that will accept you. Addiction medicine has been very accepting of people who are in recovery, and this makes sense. Indeed, many of counselors enter the field this way.  So yes, there are doctors who enter the field through that route. From your own organizational research you know another important issue, too. Stigma applied to unpopular patients is often put on the providers, too.

HP: Let's talk a bit about the diversion issue. How should policy makers and the public think about balancing the costs and benefits that come from expanding access to valuable treatments that also create new channels for people to illegally divert the product, and may exacerbate some of our black-market problems depicted in the story?

PF: No one in the field is surprised by the presence of an illegal market here. The fact that buprenorphine is a partial agonist means that it’s an effective treatment, but it also means that there is likely to be a secondary market for it. I see a lot of people come in to treatment after having tried Suboxone on the street. There are a lot of people out there who use it to self-treat. I'm sure there are plenty of people who have antibiotics in their medicine cabinet and when they get a cold they self-treat, as well. Ironically in the case of buprenorphine, some people who otherwise who wouldn't have access to treatment are able to try it out and then end up coming into treatment.

There are clearly some kids who have used anything and probably injected and snorted it. The Times described this; the issue does exist. When we consider oxycodone and any number of other medications that cause problems, buprenorphine is probably not the drug of their choice for most opiate users.

HP: When Suboxone was first marketed, the manufacturers argued that it had very limited abuse potential.

PF: It was always known that the product had abuse potential. We had experience from Europe indicating that. The addition of Naloxone to buprenorphine in the Suboxone formulation was designed to try to mitigate some of the abuse potential. As I mentioned, Naloxone is a full antagonist. It doesn't have any real action if you take it the way you're supposed to, sublingually. But if you crush the medication and inject it, then you would get the antagonist effect. The thought was this formulation would attenuate some of the abuse potential.

With all such medications, the pharmaceutical effects are double-edged swords. Properties that make for effective medications also create some abuse potential. There’s no question. You have to remember that we tried full antagonist, naltrexone pills in the past. What we found was patients would not take the medicine because it had no agonist effect at all. It did not make the patients feel normal. What buprenorphine does, because it has a slight agonist effect, is to create some reinforcement for patients to take their medication.

To me, the issue is one of properly balancing these concerns. I think this article greatly overstates the extent of the problem, while it under-appreciates how life-saving buprenorphine has been for many people.

Tyranny of the availability heuristic

HP: Part of the problem comes back to familiar problems of risk-perception. In the aggregate statistics, buprenorphine prevents many overdose deaths. It helps many people. There's no question in my mind and in the mind of many drug policy experts that there would be more opiate overdose deaths if buprenorphine weren’t there. At the same time, a smaller number of identified people will abuse buprenorphine and experience very dramatic bad outcomes. Even more will have such outcomes associated with methadone, which is involved in much larger numbers of overdose deaths than buprenorphine is. 

So we can easily cite specific examples where buprenorphine has been horribly abused with tragic results. Meanwhile the much larger benefits are more diffused in the population, and are therefore more readily overlooked or underestimated. This is not a new problem in public policy. Anti-depressants likely prevent many youth suicides. Yet highly-publicized suicides committed by young people taking these medications produced calls for black-box warning labels that probably cost many lives.

PF: That's absolutely true. When somebody takes a medication and dies, that's very vivid. When somebody takes a medication and goes on to proceed quietly with their life, it doesn't show up on anybody's radar screen. There are a lot of those unseen people out there. It's the same for methadone. You hear all these harsh stories about methadone, but you never hear about the tens or hundreds of thousands of people who are taking methadone everyday, who work, who have largely conquered their habits and lead normal lives. You never hear about those people.

Overdose and the loss of tolerance

HP: Many overdose deaths involved people who somehow compromise their tolerance, people who have been abstinent in treatment or were recently released from correctional settings. Other people have in various ways altered their regular use. So when they relapse, or when they have an unexpectedly severe reaction to opiate doses they were previously accustomed to, you might find buprenorphine or methadone in their systems. Ironically, the risk of fatal overdose seems to increases when people are trying to stop, when they are going through an abstinence period and are less tolerant than they expect to be.

A noted study by John Strang and collaborators examined mortality and overdose deaths among 137 consecutive patients admitted to an opiate treatment program. Patients who successfully detoxed and those who had long stays in residential treatment were more likely than patients who quickly relapsed to experience fatal overdose.

PF: Numerous studies have shown that substitution therapy with methadone or buprenorphine prevents overdose deaths. There's also the notion that something like Suboxone, or methadone for that matter, is so long-acting that you'll continue for a week or two to have positive urine toxicology. If you come in and overdose from alcohol and benzodiazepine and you have methadone in your system, it will often be attributed to the methadone, when it's probably a lot of the sedatives and alcohol that are out there that are doing as much damage. I fear we will see buprenorphine unfairly blamed for outcomes the buprenorphine didn’t really cause and actually often prevents.

Improving regulation of incompetent or unethical providers

HP: Let's come back to some of the genuine abuses and regulatory failures. Before we get into that, can you describe for readers the unusual limits that are placed on physicians in prescribing buprenorphine?

PF: This medication was rolled out through a partnership between the federal government and manufacturer. The notion was to make addiction more of a primary care disease. Primary care docs would take on more of this problem. It wouldn't be specialized. The Drug Abuse Treatment Act of 2000 set things up so that initially docs would be limited to 30 patients on this medication at any one time. The law was subsequently revised. So after one year of prescribing, a physician could have 100 patients.

So, what it's done is set up these limits in terms of how many patients you can have. It's also basically said that you can't have a specialization in doing only this, which is contrary to everything else in medicine (or our society for that matter) where specialization has led to great strides.

This also creates a scarcity of slots, with perverse consequences. If I only have 100 slots and I need to pay my rent, am I going to accept Medicaid patients with low reimbursement rates? Or am I going to set up a cash practice to try to use the scarce resource (i.e. these slots) to pay my bills?

We also set up a system in which the ability to enter the field, the bar, is fairly low. All you have to do as a physician is to take an eight-hour online course. And as long as you're a prescriber, you can start doing this. From a physician perspective, the bar is pretty low in having to show any expertise in doing this. That’s not the way we dispense other medications for complex conditions. The law’s low patient limits also suggest that there's no real point in you getting a specialization in this, because you're not going to be able to build a practice.

So those two things have created a scarcity of slots with good providers, while attracting a number of providers out there of varying quality. The low bar for entry allows many people of questionable skill to enter the field, and in some cases, providers with questionable ethics.

I've heard it spoken of as a gold rush. This is an easy way to make cash and that's the sort of the system that is set up. In the meanwhile, if you're a Medicaid patient, it's very difficult to gain proper access using only your insurance.

HP: As the article notes, a for-profit clinic can charge a $100 for a weekly visit. If you maintain a 100-patient active practice, that's a half-million dollars a year. In a different regulatory set up, you might say that an expert such as Pete Friedmann should be allowed to treat a much larger number of patients, and that maybe there should be a higher barrier for entry at the low end. There is one challenge with that. It goes against the aspiration to have these disorders addressed in primary care.

PF: We have to decide what we’re trying to do here. Is this like treating simple hypertension, or is this like treating somebody who's having a myocardial infarction. We don't treat heart attacks in primary care. People with severe disorders need better access to good care. Some people with fairly mild disorders could be treated in primary care, but right now, we don't have a way to really do this well. Docs have been notoriously resistant to gaining the skills they need to really do this. The hope was that the Drug Abuse Act would push them in this direction. It’s not clear that docs really embraced this change.

HP: There's a genuine tension. We need better ways to help patients who are deterred by the stigma of the specialty addiction system. They may never come to see you. They might be willing to be seen by their primary care doctor.

PF: At least some of the stigma surrounding the specialty system has to do with  various requirements and restrictions patients experience in the methadone system. I think primary care docs still need skills in identifying people with these problems and helping to ensure that these patients get the care that they need. But you're right; there is a real tension. This isn’t a new problem. Some primary care docs have gained skill in treating HIV or high blood pressure or diabetes.  There are certainly primary care docs who can gain the necessarily skills.  I just feel that the bar for entry is too low and the limits for those with real specialization are too stringent.

I should also mention something else. I'm not talking about limiting this to the specialty addiction system. I'm saying you need the physician specialist, which is what we're doing at ABAM (American Board of Addiction Medicine). We're trying to create a physician specialty that specifically addresses these disorders and having sufficient physician workforce with the needed expertise to be able to help manage these patients. The current specialty treatment system is very separate from mainstream medicine. It's its own entity with its own history and development.

HP: So you'd still be coming to a standard medical provider—maybe University of Chicago Medical Center, Department of Internal Medicine or Psychiatry—where you would get specialty care that’s well integrated with the rest of your medical care.

PF: There should be a division of the addiction medicine where you'd go and you'd be seen at the University of Chicago. It wouldn't be just recovering people with a certificate in addiction counseling. You'd actually see professionals using evidence-based state of the art practices in counseling and medication and support services to manage both your primary disease, the addiction, but also the ancillary problems such as HIV or hepatitis C that you might have. Many medical centers have comprehensive diabetes centers. We need a system in which there is room for having comprehensive addiction treatment centers in places like the University of Chicago.

Harold Pollack is the Helen Ross professor at the School of Social Service Administration and co-director of the Crime Lab at the University of Chicago. He is a nonresident fellow of the Century Foundation.

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