A physician explains how “precision medicine” can lead to comprehensive recovery.
It is well known that the field of medicine has been slow to welcome addiction as a treatable condition, contributing to the stigmatization of substance misusers and causing them to seek help outside of the medical community. Thankfully, all of that is now changing with advances in the field of addiction medicine and the development of new treatments specifically targeting addiction. Dr. Howard Wetsman argues that most addiction treatment has been misguided and ineffective but that we are finally able to “throw away the cookie cutter” and “treat addiction like the disease it is.”…Richard Juman, PsyD
We use the word “disease” a lot in addiction treatment. We’re proud of our “disease model” and like to talk about how it is such an advance on the stigmatizing old “moral model.” We talk about the techniques that we use to treat the disease of addiction and how people get better in response. There’s only one problem: We don’t really believe that addiction is a disease!
Most of how we think about [addiction], research it, diagnose it, pay for it and treat it is wrong.
I say that because, in spite of the language that we use in describing addiction as a disease, we don’t actually treat it like it is a disease. In working with patients that have chronic illnesses, physicians routinely put patients on medications with the intention of the patient staying on the medication indefinitely. Examples of this would be cholesterol-lowering medicine for heart disease, insulin for diabetes, beta blockers for high blood pressure, etc. Would we ever tell someone who had one of these chronic illnesses that they should take their medication for six weeks, or three months, or even two years, and then stop, unless their condition had been fully treated? I think even the least-educated layperson would understand that’s not a logical strategy. Yet, it is routine practice in addiction treatment to tell a patient to take a medication for a brief period, “until your brain normalizes,” and then stop. That is simply not an evidence-based practice in medicine, and indicates how far we still are from thinking of and treating addiction as a real disease.
For instance, I recently went to see my internist who was late to the appointment. He apologized and I asked what happened: “An old patient of yours,” he replied. “Really,” I asked, “Who?” He told me the name; I remembered her from about eight years ago. She had done well on buprenorphine maintenance until I closed my private practice to work at a treatment center. She had evidently gone to see someone else who thought that buprenorphine wasn’t consistent with being “sober.” In the years since I’d treated her successfully with ongoing buprenorphine, the medication was discontinued, she had gone back to using a few times, gone to inpatient treatment twice at centers that didn’t use buprenorphine, and been to a few psychiatrists who had treated her for other diagnoses. He told me she had never done as well as when she had been on buprenorphine, and that he had put her on it at the old dose a few weeks ago and she was doing fine.
“So what’s the problem?” I asked, “Why did it make you late?” “Because her parents and husband want her off the medication,” he said. He went on to explain that over the last seven years the advice she and her family had been given about buprenorphine was that it was only a short-term medication until “her brain normalized.” The mindset behind this advice is that addiction is really just a long-lasting intoxication that will eventually go away, leaving the person normal again; this is not a true understanding of addiction as a disease.
My internist knows the definition of disease: the loss of some function of some part or organ of the body. It is pretty clear in diabetes what organ doesn’t work. It’s pretty clear in emphysema what part has lost some function—in addiction, not so much. To meet this problem in understanding addiction, scientists have sought and found a tortured biochemical pathway of second messengers and enzymes that change when lab animals are given drugs. We use this pathway to explain what happens to the normal brain on drugs and how the “disease” happens. But it still doesn’t answer why the person took the first and second doses of the drug. For that, we invoke many other personality and psychiatric problems that bring us perilously close to the moral model.
With every other chronic disease we look at data. With addiction, we believe.
As long as we think of addiction as something a “normal person” has done to himself by using a drug, we will only see it as a temporary abnormality brought on by bad behavior. We will continue to expect that person to “return to normal,” “get better and not need medications,” and “be clean (including no medicines) and sober.” We don’t expect that in a person with decreased insulin production. We don’t expect that in a person whose pulmonary alveoli have lost integrity. We don’t expect that in any other chronic disease. That’s because with every other chronic disease we look at data. With addiction, we believe.
We believe in lots of things that help explain to us why we can call addiction a disease even when we don’t treat it that way. One of them is Post Acute Withdrawal Syndrome (PAWS). This syndrome (as a dog lover I think the name is very cute) explains to us why people who have recently withdrawn from a drug such as an opioid might be feeling poorly months later. It explains to us that drug use is long lasting without invoking a permanent physiological change. I’m not suggesting that there aren’t long-lasting changes from an environmental assault such as chronic drug use, but only that there is another, more primary, explanation of the phenomenon.
We need PAWS to explain the phenomenon because we don’t believe addiction is really a primary disease. Here’s a case I had that explains why: I treated a 54-year-old woman (details changed and obscured to protect her identity) who had no indication of a DSM Substance Use Disorder or other mental illness until she was 45, when she took a prescribed opioid for pain after a physical trauma. She loved it; “best feeling ever.” She noticed that she could get things done, wasn’t scared of other people anymore, and was far kinder to her husband and children with an opioid onboard. It’s always wonderful at the beginning. But notice her reaction to this “narcotic” drug: It wasn’t narcotic—it was stimulating. Narcotic means “to produce sleep,” but opioids woke this woman up, as they do to about 10% of the population that don’t normally release enough dopamine. These people therefore get an increased dopamine signal from something that releases dopamine, like an opioid. Still, so far she’s a fairly normal-sounding opioid dependent patient.
Her next decade wasn’t pretty: dose escalation, increased alcohol use, addition of amphetamines, a lot of scheming to get opioids, crossing lines she thought she’d never cross, the usual. So she came for treatment, refused IOP or inpatient treatment, and we discussed buprenorphine, among other options. She stopped her pills, entered moderate withdrawal and I titrated her up to 16mg a day of buprenorphine. Withdrawal went away and she felt much better. So far, so good. So far, this is a picture most people who treat addiction and call it a disease can identify with.
And here’s where things change direction: a couple of weeks later she told me that she was much better, but there was still something missing. She didn’t have much “get up and go;” she felt blunted; she found she was more irritable with her family. She’d wanted me to give her an amphetamine for ADD because they had helped her so much when she couldn’t get opioids before. At this point, most people are having one of two reactions, which I will simplify into a false dichotomy for illustration. The first reaction is from the school that believes that addicts just want to get high; this group would argue that her wanting amphetamine on top of buprenorphine is an example of a deeper character flaw, a need for extended inpatient treatment, and an example of why buprenorphine isn’t really addiction treatment. The other reaction is that her continued symptoms are real, an example of PAWS, and that this is an indication for getting her off buprenorphine and onto naltrexone to combat her opioid receptor accommodation and end her PAWS. The second school would call the first school a “bad” name, like the moral model, and call itself the disease model. Remember, this is a false dichotomy. Don’t take it personally!
So what did I do? Genetic testing. I found that she had a polymorphism of Methylenetetrahydrofolate Reductase (MTHFR), an enzyme that turns folic acid from our diet into L-methylfolate, the only form that our brains can use. One use for L-methylfolate is as a co-enzyme in two stages of the production of dopamine. This polymorphism decreased the function of MTHFR so that she didn’t produce as much dopamine as normal. The other thing I found out is that she had a polymorphism of Monoamine Oxidase B (MAOB), an enzyme that breaks down dopamine. Her polymorphism increased MAOB function so that she broke down dopamine too fast, before it could be packaged in a vesicle for release. This meant that her dopamine-releasing vesicles were never packed with as many dopamine molecules as they should have been.
So, I started her on a prescription form of L-methylfolate to supplement what she was missing. When she wasn’t well a few days later, I started her on a selegiline, a selective MAOB inhibitor. What other clinicians would have described as PAWS went away. The point is that her PAWS went away as I increased dopamine tone, not as her opioid receptors lost accommodation. It wasn’t PAWS, what she had was partially treated addiction. Buprenorphine was only part of the treatment because opioids were only part of the problem. I’ve had several patients like her that could never have come off of buprenorphine without the addition of other medications that were genetically indicated to raise dopamine release. She did get off of buprenorphine, but has stayed on L-methylfolate and selegiline.
I also talked to her about 12-step recovery from the very beginning of treatment. I do that for two reasons. The first is that I’m a doctor and I’ll use whatever works, and 12-step recovery works in many people. The second is that I’m a doctor who was trying to raise her dopamine tone to relieve her primary symptoms of addiction, and 12-step recovery is the best way I know of increasing dopamine receptors by stopping isolation and “feeling less than.”
In spite of my urgings, this woman did not attend meetings, get a sponsor, or, most importantly, work the steps. I did 12-step facilitation therapy (TSF) instead, but that’s a pale substitute for daily practice. I am the Chief Medical Officer of a treatment company whose goal it is to get as many people into recovery as we can. I view addiction as a chronic and progressive disease and am a big believer in recovery communities that allow for lifelong participation beyond treatment because the support and fellowship that such groups provide is an important element of long-term recovery.
I think the world changed when, a few years ago, the American Society of Addiction Medicine published its definition of addiction. Instead of a categorization of behaviors, it’s a definition worthy of an actual illness, based in biology and developed from essential principles.
There are several points of ASAM’s definition that represented a paradigm shift, and these are encompassed in the first three sentences, which I’ll include here:
“Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry. Dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations. This is reflected in an individual pathologically pursuing reward and/or relief by substance use and other behaviors.”
The first thing to notice is that the illness is primary. That means it doesn’t have to have a cause. It can be there first. Next, notice the order. Illness first, then symptoms and signs, that are in turn reflected by the substance use. The exact opposite of the paradigm in which substance use causes the signs and symptoms that define the disease. Next, notice the last words, “other behaviors.” Addiction is not limited to drugs, and once you accept that, you have to have a way of explaining it other than “the drugs did it.”
So, what are the implications of understanding that addiction is a disease? It means that most of how we think about it, research it, diagnose it, pay for it and treat it is wrong. It means that we now have a good explanation of why, after decades of thinking about addiction as something caused by drugs, and billions of dollars spent trying to treat addiction along these lines, the problem is no better. But, now we have a way forward.
We are now able to look at the genetics and do early recognition before a person ever picks up their first drug. We can look at the epigenetic factors, other than drugs (poverty, social injustice, physical isolation, etc.), that affect normal brains and aim our prevention efforts where they’ll actually work. We can have real medical treatment, both short term and long term, combined with the non-medical treatments that have been shown to impact the disease biology and say who will benefit from each. We can throw away the cookie cutter, and we can take a lot of people we thought were hopeless and get them real, comprehensive treatment, rather than say that the best they can expect is harm reduction.
We can finally treat addiction like the disease it is in nature.
Howard C. Wetsman, MD, is the Chief Medical Officer of the Townsend Addiction Treatment Centers in Louisiana and the author of Questions and Answers on Addiction.