Saturday, October 20, 2018

The NEJM "Addiction As Learning And Not Disease" Article




The latest installment of what appears to be an endless debate about whether addiction is a disease or not hit this weeks New England Journal of Medicine in an article entitled "Brain Change in Addiction as Learning and Not Disease." I have looked at a few of the previous articles along the same line that purport to show why addiction is not a disease and it is fairly easy to show that disease or not a disease generally depends on the author's definition and pointing out why the other definitions do not seem to fit. It is basically an exercise in rhetoric.  Those approaches invariably end up at quite a distance from opinion polls that illustrate that most of the public and even more medical professionals consider addiction and severe mental illnesses to be diseases.  I will come back to the philosophical underpinnings of those polls at the end of this article.

In this case the author is essentially making three arguments.  Two of the arguments are in side panel graphics and the third argument is in the main text.  The first side panel argument (p. 1552) concerns the Brain Disease Model and Stigma. In it the points out that the disease model can be destigmatizing but it also can be stigmatizing to some people.  Although I do not agree with some of his premises let us accept that his argument is basically a wash and the people who feel stigmatized and recoil from the prospect of the addiction illness perfectly cancel out those that accept the model are are consoled by it. I recognize that a substantial part of the recovery community base their recovery work on the disease concept of addiction although it is not strictly similar to the biomedical disease that is typically described.  This entire panel described a sociocultural model of disease (2).  This concept is basically that different societies and the physicians in that society may have diverse views of diseases that vary from other cultures.  A secondary factor is that medical recognition may change how that disease has come to be viewed by the society at large.  For example, an illness that was once thought be be caused by moral deficiency is seen differently after it is recognized as a process that may be beyond the control of the afflicted person.  Mental illness, alcoholism, and addiction are common examples.  An associated feature of this model is that this concept cannot be used by the medical field that must concentrate on understanding the biological mechanisms that underlie the disease.  The makes this panel irrelevant to a medical disease concept.

The second side panel (p 1553) looks at Learning Models and Empowerment.  It can also be understood as a sociocultural model.  In this panel the author develops a number of arguments to suggest that if people were free of thinking they had a disease they would be more prone to self examination and less dependent on professionals and the need to adhere to what professionals tell them.  He suggests that disease mechanisms would lead to pessimism on the part of the person with the problem that would not exist if they were engaged in any number of learning programs to help them recover.  He uses the familiar quote that most people recover spontaneously without any help from professionals.  This argument depends on a couple of premises that are clearly flawed.  The first is the group that is described as having an addiction.  The convention I use for that is Volkow's definition of being equivalent to severe DSM-5 substance use disorder in any category.  That category has a high level or mortality, comorbidity, and chronicity. In this case the author seems to minimize the interventions used by addiction professionals to "making life-style choices to improve their prognosis."  That minimization serves his purpose to suggest that learning is an entirely novel approach to addiction when it has been used for decades.  Spontaneous recovery is an often quoted argument against a disease model, when it happens all the time in other conditions (obesity, metabolic syndrome, diabetes mellitus Type II, hypertension).  The fact is, spontaneous recovery by any number of conscious interventions does not preclude a disease process.

The bulk of the author's argument in the main text is based on illustrating how learning in addiction and normal learning are similar if not identical processes and therefore disease is a learning problem rather than a disease.  The most logical way to analyze this argument is to examine the conclusions first.  Looking at the conclusion highlights the seriously flawed premises in the author's argument that addiction is not a disease but is just learning.  I did not see any qualifiers that addiction is a special case of learning or not.

The author's believes that he has developed a "balanced model of addiction" that incorporates various learning mechanisms into what he calls and "embodied cognition model" of addiction.  In this model he sees baseline and adaptive biology interacting with the environment to produce the addiction.  It is interesting that the key environmental feature of drug use disorders - exposure to the drug is way down his list of other social, cultural and familial factors.  Some of his examples illustrate this point.

He discusses the socially disadvantaged youth raised in an adverse environment: "These persons tend to find increased meaning in drugs that reduce stress or promote feelings of security and well being especially because these effects can be attained without medication by other people." That does not explain the flood of advantaged white middle class youths who became addicted to heroin and represent a substantial number of overdose deaths.  It also does not explain the difference between two inner city youths who have to walk past 3 drug dealers on their way to school each day and one of them becomes addicted and the other does not.  One of the important lessons of the current  opioid epidemic should be that exposure to a highly addicting drug in biologically predisposed people is one of the central mechanisms of addiction.     

The authors "addiction spiral" is also problematic.  It begins with "early adversity and trauma" as the first step effectively limiting any explanatory power to that population. In step 2, he discusses development changes in the autonomic nervous system that may occur in response to childhood trauma that can lead to hypercortisolemia as an adult. That makes this model appropriate only for adults who have been traumatized as children and even then - only those children with this pathophysiology.  There can be a broad range of factors that lead to behavioral inhibition and anxious temperament (3). In step 3, he discusses early childhood adversity as a cause of epigenetic changes that can predispose to addiction.  He omits the concept that exposure to compounds like nicotine and other addictive substances are much more potent causes of an array of epigenetic changes and correlate highly with addiction. Kandel and Kandel (4) among others have shown that DNA hyperacetylation from nicotine is associated with cocaine use.  Epigenetic changes from drugs of abuse are widespread .  A recent study of the impact of smoking on the human genome concluded that as many as one third of genes in the human genome can be affected (5) by methylation of 18,760 statistically significant cytosine-phosphate-guanine sites. In order to claim a more potent learning effect at least an equivalent neurobiology of learning with equivalent impact that it applies across the entire population of people with addictions should be presented.  I don't think this paper reaches that threshold.   

That brings me to the point of whether it is relevant to use the disease concept at all.  I am sure that students have heard me say from time to time that it is not. That statement is usually accompanied by the statement that it still has to be recognized as a severe problem that is a significant cause of mortality and morbidity.  There is a little used philosophical approach to the disease concept that I have rarely heard about outside of reference 2.  That concept is disease as a departure from normal functioning (p 160).  In this discussion the authors develop the concept that organisms are a special case of programmed systems.  Normal homeostasis in humans is a result of that programming.  Biomedical research is focused on being able to discover that program and how it is coded, uncoded, and expressed as disease.  One of the authors' conclusions is:

"There is reason to believe that as research progresses, more and more biological processes at all levels of organization will come to be understood as programmed processes."

They refer to closed programming that are those resulting from direct decoding of the genome with inborn errors of metabolism being a key example.  Other phenomenon require an interaction with the environment to result in the full development of the programmed process.  They go on to suggest the existence of "open" programming where some form of learning or conditioning is required to complete the process.  Some of the programs may be "closed" at a certain point and not amenable to further decoding.  All of these programs are shaped by the evolutionary process.  Viewing organisms as biologically programmed systems (p 163) takes social values and norms out of the equation and provides a definition of normal functioning and it also defines the acceptable evidence necessary to delineate abnormal functioning.  The authors' straightforward definition of disease is given below:

"Disease is a failure of normal functioning."

Consider the following vignettes to illustrate that definition. None of the subjects noted had any adverse childhood experiences or pre-existing psychiatric disorders.  They all had positive family histories of addiction.

Patient 1: 22 year old woman who received hydrocodone after her wisdom teeth were removed at age 20.  She received a 14 day prescription and continued to take it even when her pain was gone.  At this point she started to acquire opioids from nonmedical sources and eventually switched to heroin for economic reasons and was injecting herself 4-6 times per day.  She went to treatment and was placed on buprenorphine-naloxone 16 mg/day.  On that dose she had no cravings for opioids and no withdrawal symptoms.  Her family has decided to withdrawal support based on considerable expenditures for various therapies that have been ineffective. She goes to a sober house but after a week there learns that there are fentanyl based products available.  She leaves the sober house in search of these products.

Patient 2:  45 year old man who is an IT professional.  His father and grandfather were alcoholics.  His grandfather died of cirrhosis. He decided at an early age that he needed to avoid alcohol in order to avoid alcoholism and did well with that strategy until about age 40.  At that point professional pressures to socialize with clients lead to some drinking that he escalated at home.  He can work from home and his drinking escalated significantly to the point he was drinking a liter a day of vodka that he consumed between 7PM and midnight.  This pattern continued for several years until he started to get episodes of alcoholic pancreatitis that required longer and more complex hospitalizations. He tried to stop drinking on his own.  He tried online courses that used cognitive behavioral therapy.  He went to Rational Recovery and eventually AA. Nothing worked and he knew that every episode of pancreatitis at this point was life threatening.       

Patient 3: 30 year old carpenter with no previous history of substance use. He was working in a new construction area and found one of his coworkers inhaling paint out of a plastic bag.  He tried it and experienced an intense episode of euphoria.  That night he went home and found Internet sites where solvent-inhalant users compare their experiences and give tips on usage. He picked up a popular computer duster product and was soon inhaling many cans a day. He eventually crashed his truck while inhaling the solvents and as the police pulled him out of the vehicle - he was still inhaling the solvent. When he was seen in the emergency department he told the physician there that he could not stop using inhalants because: "It felt like pure dopamine was coursing through my veins!"

The previous examples are not extreme cases in addiction medicine and addiction psychiatry. They illustrate a failure of normal functioning by compulsive use of a substance despite knowing that this use is irrational and repeated failures to stop.  One of the common comments about the majority of people with addiction stopping on their own totally ignores the people being seen in addiction settings.  It is this combination of severity, inability to stop despite severe consequences, and chronicity that leads physicians and lay persons alike to consider addiction as a disease.

What about the evidence of failure?  It can come in various forms.  In a standard medical format there is a signature clinical course or phenomenology of the illness.  Symptoms can be obvious in a physical or mental status exam. Laboratory testing including chemical and microbiological analyses, electrophysiological studies, imaging studies of various regions and tissues can be undertaken.  In all of these determinations the evidence can always be equivocal, false positive, false negative, or truly positive.  It often takes a level of expertise to interpret the evidence and a good example is electrocardiography.   

From a philosophical standpoint the authors in reference 2 point out the initial value of a functional-failure model of disease.  It has obvious implications for basic science research of disease mechanisms.  That research should be focused on discovering the programming errors in the human organism that results in failure of normal functioning with the hope of understanding the underlying pathophysiology and correcting it.  The model clarifies a role for statistics in the disease model specifically the strength of association of certain variables with normal and abnormal functioning as well as ways to analyze tests for those variables.  And finally, the concept makes it very clear that the disease in question is real and exists independently of societal biases.  I don't think for example that any of the above vignettes could be considered anything less than a failure of normal functioning. In the people addiction specialists treat, there is generally a trajectory of progressive isolation, multiple psychosocial losses, loss of relationships, poverty associated with addiction, and in too many cases - premature death due to the direct or indirect results of addiction.

That is the reality and it is captured by disease as a loss of normal functioning.

I am going to bring this post to a close at this point, but look for a more extensive look at the specific types of learning listed in this article compared with the biological impact on plasticity when people are exposed to addictive drugs.  I started out thinking that I was just going to continue my opinion about the disease concept being irrelevant but instead find that I have been invigorated by a view from a book I read over 20 years ago that is still relevant today.  I will end with a communication I received from one of the authors that I hope sums up this post and illustrates why physicians should probably not cloud the disease concept with popular notions like stigma or  empowerment:

"Most people would think epistemology is always irrelevant to ordinary life, but clearly it isn’t."


George Dawson, MD, DFAPA



References:


1: Lewis M. Brain Change in Addiction as Learning, Not Disease. N Engl J Med.2018 Oct 18;379(16):1551-1560. doi: 10.1056/NEJMra1602872. PubMed PMID: 30332573

2:  Albert DA, Munson R, Resnik MD.  Reasoning in Medicine: An Introduction to Clinical Inference.  Baltimore, Maryland: The Johns Hopkins University Press, 1988: 150-180.

3: Fox AS, Kalin NH. A translational neuroscience approach to understanding the development of social anxiety disorder and its pathophysiology. Am J Psychiatry. 2014 Nov 1;171(11):1162-73. doi: 10.1176/appi.ajp.2014.14040449. Review. PubMed PMID: 25157566.

4:  Kandel ER, Kandel DB. A Molecular Basis for Nicotine as a Gateway Drug. The New England journal of medicine. 2014;371(10):932-943. doi:10.1056/NEJMsa1405092.

5: Vaillancourt K, Ernst C, Mash D, Turecki G. DNA Methylation Dynamics and Cocaine in the Brain: Progress and Prospects. Genes (Basel). 2017 May 12;8(5). pii: E138. doi: 10.3390/genes8050138. Review. PubMed PMID: 28498318.

5:  Joehanes R, Just AC, Marioni RE, et al. Epigenetic Signatures of Cigarette Smoking. 2016. Circulation: Cardiovascular Genetics. 2016;9: 436–447. Full text


Supplementary 1:

My thanks to both Ron Munson and Mike Resnik two of the authors of Reasoning in Medicine - reference 2 above.  Further thanks for Ron Munson for the quote at the end of this post and encouragement to explore his ideas about the disease concept.  It means a lot to hear from both of these authors at a point when they could have easily ignored me.  It is a sign that there are many kind and thoughtful scholars out there. 

As I type this at 2AM that thought about scholars gives me a warm feeling.


Supplementary 2:

The quote used for patient 3 is found on the Internet and used for this hypothetical patient.  I have feedback from at least one addiction psychiatrist that the vignettes provided above are realistic and typical of addiction psychiatry practice.




1 comment:

  1. I have been practicing for 25 years, and I have not seen anything deter me from my paradigm about addiction, which is the following:

    there is a genetic basis to about 1/2 of the addiction population; there is about a 1/2 that is based on self medicating; there is about 1/4 that is about serendipity exposure to substances that leads to dependency, and there is about an 1/8 that is purely a sensation seeking model of use to seek out euphoric experiences. Yes, they add up to more than 1, as there are overlaps with these patients having more than one factor to their developing dependency/addiction. The Sensation Seeking folks are the ones who most likely can get out as unscathed as possible because they get bored with the addiction experience and move on to other experiences with some ease. The Serendipity folks seem to overlap with both the genetic risk group and self medicating group, but, they too seem to move out of addiction with some ease if not too embedded with a "support"system that sabotages their efforts to get out.

    The last two, the genetic and self medicating groups, why they are at least 1/2 the population of addicts each, more likely more than 50% for each, but, when they overlap, these are the multi factored group hardest to see maintain abstinence, because the genes AND the self medicating are so hard to reframe and commit to alternative models of stability.

    By the way, sorry for my more usual side bars, but, the Suboxone model has really deteriorated into Methadone 2.0, and frankly, even more heinous when one considers how much pure cash these providers are hauling in the way Suboxone is still being managed as of now.

    Where I am now, what a farce at hand, Suboxone providers are "mandating" patients see a therapist for psychotherapy to stay on Suboxone. HAH! They are just trying to find a scapegoat to legitimize these patients accessing other controlled substances the Suboxone Providers know they will get heinously gigged if they stupidly wrote for benzos and stimulants!

    Thank God I am I done this assignment in 5 weeks. Frankly, I cringe when I pick up an eval chart and see Suboxone or Buprenorphine in the intake section....

    ...as these therapists want someone to bail them out from having to take these patients on alone!....

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