Policy Makers Are Always The Weakest Link In Healthcare

When it comes to solutions to the opioid epidemic - talk is cheap. The last 20 years everybody has “the solution”. The AMA came up with a new version of theirs entitled “AMA Opioid Task Force Recommendations for Policymakers.”  Inspection of this page shows that it is basically a rehash of everything we have known over the past 10 years or longer. The only new message is that the AMA is now suggesting that policymakers should follow these recommendations. In this era of patient empowerment, direct advice to patients is completely missing.

Drug legalization advocates have apparently vilified the Reagan era “Just Say No” campaign to the point that attempts at primary prevention of substance use are now politically incorrect and forbidden. How can you possibly stop opioid and methamphetamine epidemics when there is a large and vocal advocacy for legalizing all drugs emboldened by the cannabis campaign? There are few reasonable voices out there saying “You know you can really live a better life without drugs or alcohol”.

It should probably come as no surprise that real action on the drug epidemic cannot be expected from a government that is unable to end a decades long streak of mass shootings. We hear the familiar refrain that people were “in the wrong place at the wrong time” or that they are “fallen heroes” and that “now is the time to move on”. A real adaptive response to mass shooting like even slightly tougher gun laws would make a difference. Despite hearing that “this is the last time that our children can be victimized” the mass shooting saga drags on - courtesy of local and federal governments.

The resolution of the opioid epidemic is another example of how our government doesn’t work on serious public health issues.  The epidemic has been in place for the past 20 years.  Using deaths by overdose as a proxy measure suggests that things may be improving the last couple of years, but the epidemic is far from resolved.  The more recent problem has been that people who started using prescription opioids have changed to heroin or fentanyl – the supplies of both are plentiful and less expensive than the street value of typically prescribed opioid pain tablets.

A few words about the points the AMA has in their graphic:

1. MAT - medication assisted treatment for opioid use disorder is considered a major advance in treatment. That applies both to methadone maintenance treatment and more recently buprenorphine maintenance with various preparations. Sustained-release naltrexone injections are also an option but they are more controversial due to the longer induction and wait time until the patient is safely covered by opioid receptor antagonism. The current AMA position is to remove prior authorization from these treatments so that they are more readily available. Some treatments are more cost-effective than others. It is not clear from the statement how the AMA hopes to remove these barriers particularly since they have not been effective in removing them for the past 30 years of utilization management or prior authorization. They may be counting on political leverage in this case but I don’t see it happening. Regulators and politicians could easily make this an exception to the current utilization management and prior authorization statutes that they have on the books but it should be apparent from that statement that they are the problem in the first place.

2. Mental health - the document cites the well-known correlation between mental illness and substance use. The document also cites the Mental Health Parity Addiction and Equity Act (MHPAEA) as meaningful but the only way this law gets enforced is if civil action is brought against healthcare companies. These healthcare companies are protected by legislation and they basically do whatever they want. The AMA Task Force suggests that healthcare company should be “held accountable” but that hasn’t happened in the 10 years since the MHPAEA has been passed.  The document suggests that a number of addiction specialists should be in the networks of these healthcare providers, but for 20 years politicians have been rationing mental health services to the point that county jails are currently our largest psychiatric institutions. The mental health suggestion in this document seems like another wish.

3. Comprehensive pain care and rehabilitation access - I would really like to see the numbers on this one. If anything there has been a tremendous proliferation of freestanding or chains of pain clinics over the past 20 years. That proliferation correlates directly with increasing opioid prescriptions. As far as I can tell there has been no movement at all in terms of determining what constitutes a quality pain clinic versus something else. This may have to do with the politics that wrung the word “quality” out of the healthcare system 30 years ago. There is also an access problem. In other words there has always been “non-opioid alternatives” like physical therapy but healthcare systems ration their utilization.  This might be another area where education is important and convincing people that a course of physical therapy even if their healthcare company makes them pay for it is potentially more beneficial than taking opioids and getting deconditioned for a period of time.

4.  Maternal and child health - there is no doubt that punishment-based paradigms can intrude on the parental relationships with children and result in destabilization of families. This usually occurs on a county by county basis and there are no statewide standards and no specific treatment facilities. The problem is compounded by the fact that most states consider social services to be as expendable as mental health services and it takes more than a suggestion to reverse that 20-year trend.  Recently, the child protection issue as a result of substance use has become so bad that additional tax legislation is needed just to cover this problem.

5. Civil and criminal justice reforms - the most significant reform suggested in this section is that MAT is continued when a person is incarcerated and after they are released. This is a tall order considering how difficult it is for anyone to access MAT in an outpatient setting. Jails and prisons have the absolute worst record. The evidence for that is people who are acutely taken off of methadone, buprenorphine, or other psychiatric medications at the time of incarceration. That can lead to weeks of opioid withdrawal symptoms and intense physical symptoms.  Despite many county jails considering themselves to be psychiatric hospitals very few of these places are equipped to assess and treat psychiatric disorders or do medication assisted treatment of substance use disorders.

That is the AMA WishList and all of its deficiencies. I have not seen a realistic assessment of the problem and how to reverse it in spite of the fact that there are two documented opioid epidemics in the medical literature and suggestions about how they were resolved. I never heard anyone referencing them. Medication assisted treatment was one component but there are other significant factors that no one seems to be talking about at this time.

Working in a residential treatment facility provides me with unique perspective on the problem. The continuum of care ranging from residential treatment to intensive outpatient treatment to date treatment to self-help groups like Alcoholics Anonymous and Narcotics Anonymous depends on a number of factors to make it work. First and foremost is a competent staff in the facility with reasonable boundaries and a supportive environment. Most medical facilities do not have this because of significant bias against people with substance use disorders. There are some treatment facilities that have similar biases and they should not be allowed to admit people until that problem is resolved. The measures recommended by the AMA Task Force are medically weighted and that means that treatment facilities need to have medical staff. If the facility needs histories and physicals done medical staff need to provide that function as well as comprehensive detoxification, treating associated medical problems, and providing psychiatric care and MAT. There is no point in having residential or outpatient treatment programs in a network if they cannot provide that level of care. People who need MAT should not be treated in facilities where they cannot get medical assessment and treatment.

That basic fact seems to be missing from the AMA Task Force guidelines, state regulations, and any discussion at the federal level about what kind of treatment is needed for people with active opioid use disorders.

The AMA could be of more service referring people to appropriately staffed treatment programs and advising the public on the source of all of these obstacles of care. As I have been writing here for years now those obstacles are a product of pro-business government policy at both the state and federal level and how those rationing businesses are able to operate. Until that basic flaw is corrected - I do not anticipate any increase in access to treatment (at least effective treatment), increased access to appropriate social services, or sudden revision of county jails to suddenly make them functional psychiatric units.

There are some changes that would make an immediate difference in the opioid epidemic instead of the continued evidence-based platitudes.  If there are any policy makers or politicians out here that are serious about making some changes - here they are:

 1:  Hold physicians harmless for providing MAT:

The suggestion that more physicians should be providing MAT for opioid use disorder has gone from a suggestion to more of a demand.  Just this weekend there have been debates about why Emergency Department Physicians aren't providing MAT for every person with OUD that they see.  My first thought when I saw that was: "Are they serious?" People are not presenting to EDs with casual use.  They are not people coming into clinic intentionally in withdrawal to start buprenorphine induction. They are generally people with very serious use problems who end up in EDs because of a different problem. Many of them are polysubstance users with multiple drugs on board and in many cases drugs that are typically flagged as having potentially serious interactions with buprenorphine.  Add to that the dearth of buprenorphine prescribers that will accept referrals from an ED and it makes perfect sense that Emergency Medicine physicians do not want to send people out with buprenorphine.

The physicians are not the problem, the practice environment is.  The solutions seem obvious to me.  The first is to indemnify the physicians for providing care that is harm reduction to patients with high risk. This already happens in state statutes that cover Good Samaritan provisions, mandatory reporting of child and adult protection concerns, and civil commitment and guardianship proceedings that hold the petitioners harmless for good faith activity.  MAT is a very similar endeavor. But I would not just stop at a vague statutory requirement. I would tie it in with abbreviated training for MAT.  When I took that training, at least half of the patient case examples were high risk with limited resources, psychiatric comorbidity, and they were using high levels of multiple substances.  The answer in each of these scenarios was to prescribe buprenorphine as a way to assist the patient with the OUD aspect of the problem. 

2:  Open up addiction clinics:

The idea that primary care physicians are all going to start seeing large volumes of these patients will not materialize as long as there is a problem with cross coverage.  I have seen it happen many times. A well intended physician starts prescribing buprenorphine and even in a mutli-specialty clinic has nobody else to assist and is on-call 24/7 for years until they burn out.  There has to be a structure in place where there are clinics that can handle large volumes of patients including the referrals from all of the local EDs and correctional facilities and provide adequate cross coverage for the physicians prescribing buprenorphine. 

3:  Decrease the training requirement:    

Unlike others - I don't think it can be eliminated for the reason I cited above.  The physicians and other prescribers need to know the high risk scenarios that they can treat.  I think it could probably be done in two hours with a case book of treatment scenarios.  The case can be made for collaborative care/mentoring arrangements with experienced physicians, but the funding of those scenarios should be seriously considered.   

4:  Provide temporary housing programs to take people directly from the ED and crisis appointments: 

As a former acute care psychiatrist - I know the uneasy feeling of providing brief opioid detox services and discharging patients with OUD to the street with medications that have street value.  There is no surer path to immediate relapse.  If we are really serious about helping people get established on MAT, they need a stable environment where it can happen. 

5:  States need to license substance use programs only if they provide medical services and MAT:   

If we are all serious about the effects of MAT in OUD it is time to start acting like it.  There is no longer an excuse or reason for not offering MAT to all patients in residential, extended care, or outpatient treatment programs.  There are no religious or ideological grounds that justify not offering these services and the license of all treatment facilities should depend on it.

These are my ideas about stopping the opioid epidemic that stop all of the platitudes in their tracks.  There is a rational way to proceed that does not depend on physicians sacrificing to keep the irrational system afloat. The rational way will cost money, but it will also save money but not in the way politicians usually talk about healthcare savings. It will save money and resources by saving lives, not investing in inadequate treatment, and finally putting a dent in the large circulating pool of opioid and polysubstance users that are circulating between emergency departments, inpatient units, drug treatment programs without MAT, detox units, shelters, and jails.    

George Dawson, MD, DFAPA

Drug Overdoses As A Proxy For Drug Epidemics

Figure 1 - Mortality rates from unintentional drug overdoses.

(A and B) Mortality rates for (A) individual drugs and (B) all drugs. Detailed data for individual drugs are only available from 1999 to 2016, although additional data for all drugs are available since 1979 (this area is grayed out). The exponential equation and fit are shown for all drugs. (Synth Opioids OTM: synthetic opioids other than methadone. This category includes fentanyl and its analogs.) from reference 1 with permission.

A recurrent topic on this blog is drug overdoses due to street drugs and the epidemiology of these overdoses.  As an addiction psychiatrist it is obvious that access to drugs and alcohol is a critical feature of epidemics and the broad exposure has resulted in increased accidental overdoses. The clearest example I can think of is the spread of heroin overdoses to rural America.  That phenomenon did not exist 20 years ago.  The implicit aspect of the access argument is that other commonly held reasons for addiction and overdose deaths like poverty, race, culture, etc are really not reasons that people get addicted to drugs and alcohol.  That happens because they have a biological predisposition and they have access. There is a lot of resistance to this basic idea because it runs counter to the idea of broad legalization of cannabis and other drugs like psychedelics. It runs counter to the idea that the war on drugs is the real problem here and the situation would improve without it.  It also runs counter to the alternate theories about substance use that some people see are identifying remediable problems like poverty and disparity.  I see those theories as being equally stigmatizing and inaccurate.

For all of these reason I was very interested in the recent paper in Science (1) that looks at accidental drug overdoses as a chronic problem rather than a discrete series of events.  The authors analyzed a total of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System, specifically the Mortality Multiple Cause Micro-data Files.  Their main finding is illustrated in Figure 1 above and that is the aggregate overdose mortality rate increases exponentially for a period of 38 years (panel B).  The individual drugs are broken out in panel A. Only accidental deaths due to drugs were included and that determination adds some element of uncertainty to the numbers.

This is probably the best place to comment on the methodology of this research and further visualizations of the data.  Inspection of the individual drug shows that there are a total of 7 drugs.  Common drugs of concern in overdose situations like benzodiazepines and z-drugs are not mentioned specifically but there is a category of unspecified drugs and unspecified options.  The supplementary material lists accidental poisoning due to antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs - not elsewhere classified, hallucinogens - not elsewhere classified, other drugs acting on the autonomic nervous system, and unspecified drugs, medicaments and biological substances.  By that description benzodiazepines, z-drugs, and other neurological and psychiatric medications are probably in that category. Poisoning by solvents or intentional use was not included. Intentional drug poisoning - both suicide and homicide was not included.  The coding of the cause of death changed substantially in 1999 providing more detail and allowing for the separation of synthetic and semi-synthetic opioids after that time. Mortality rates were calculated by drug type, age, sex, and urbanicity.

A few points from the initial graphs. Mortality curves have generally increased for all of the drugs of interest since 2010 except methadone and the unspecific drugs. By the authors definition the range of the unspecified drugs is so broad that it may conceal clear trends within subcategories like benzodiazepines and z-drugs - both important in polydrug overdoses.  The authors suggest that the variability in some of these lines like the dip in the prescription opioid line after 2010 may have been related to attempts to reduce the number of prescriptions, laws making mandatory checking for prescriptions for controlled substances prior to prescribing, and the production of a long acting and less abusable form of oxycodone in 2010.  It seems as likely that that a lot of prescription opioid users switched to heroin at that point reflected by the rapid increase in heroin death rates from 2010 to the end of the study period.  There is a time lag to 2013 and at that point the fentanyl death rates begin an even steeper curve to the end of the study period.  There is no associated decrement in the heroin or prescription opioid curve at that point suggesting that the fentanyl rates reflects a different problem from the baseline opioid death rates. Those problems could include the fact that fentanyl is much more toxic, it could be an adulterant, it could be sold as heroin by diluting it, and it could be sought out as a way to pursue a high when tolerance has developed to the original opioid being used. The authors points out that increased access to fentanyl was documented by increased seizures by law enforcement. The decrease in methadone deaths may have been due to its removal from pain formularies and  CDC initiative on discouraging use for pain medication due to excessive toxicity.

In panel B, the authors shade the area up to 1998 to show when the opioid epidemic begins.  They make the point "of particular interest is the observation that the first half of this long smooth exponential growth curve predates the opioid epidemic."  While that may be true, it is obvious graphically that the 1979-1998 curve could also be extended without the inflection point in 1998 without the superimposed opioid epidemic and significantly higher mortality rates.

The authors also examined what they referred to as drug specific subepidemics, building on their assumptions that the exponential mortality curve that they describe is due to subepidemics. Their methods of analysis included heat mapping and geospatial hotpot analysis.  I elected to license the latter image and include it below.

Figure 2 - Geospatial hotspot analysis by drug and period.

The Gi* statistics are standardized using pooled statistics across all drugs and periods. The various shades of red and blue indicate pooled standard deviations above and below the pooled mean, respectively, as shown in the legend. The small black circles indicate major cities with populations greater than 300,000 people. None of the regions were less than 2 pooled standard deviations below the pooled average. (Synth Opioids OTM: synthetic opioids other than methadone. This category includes fentanyl and its analogs.) From reference 1 with permission.

For the above geospatial hotspot analysis. the authors looked at 8 drug categories, during 4 times frames and all of the time frames are from the opioid epidemic. The only drug that showed a peak intensity and spatial distribution followed by a decline was methadone. All of the prescription and nonprescription opioids show a progressive increase during this time frame.  That patterns are also remarkable for a spread from metro areas to non-metro areas. There are some interesting geographic observations including a relatively cold spot of overdose mortality in the north central states.

Heatmap analysis (not shown) showed a bimodal distribution of mortality in 20-40 yr olds and 40 to 60 yr olds.  Heroin, synthetics, white race, male gender, and urban counties were over represented in the younger group. The older group deaths were predominately white women in rural counties using prescription opioids.  Prescription drug mortality rates four times higher in younger men than women were attributable largely to synthetic opioids.

The authors main point in the paper is that the combination of epidemics came together to compose the exponential curve after the inflection point and that there is no clear way to figure out how that happened. They emphasize the importance of understanding these forces and cite a number of possibilities including supply side components of more efficient manufacturing of drugs, better supply chains, high purities and lower prices.  These are all well known factors in why people stop using prescription opioids and fentanyl from legal sources.  They discuss sociological factors like fragmentation of communities, despair and a lack of purpose. They discuss public health interventions like community surveillance for patterns of drug use and availability of addiction treatment for secondary and tertiary prevention.

As I read the article, I thought about my model of addiction and that is biological vulnerability + access leads to addiction.  Certainly there are people who will say that the sociological concerns described by these authors can lead to the biological vulnerability, but the protective factors in some of those communities are generally ignored. The authors seem to have at least some of the data here to show that socioeconomic status and race do not determine drug epidemics. Availability determines drug epidemics and there is no better example than some of the data they present here. In addition to race, urbanization is also an example of vulnerability + access with the spread of overdose mortality out into the country side. There is an additional dimension of data here that could be used to look at these mortality rates and that is US Census data provided tract-level measures of poverty, education, crowding, and race/ethnicity. In other words how does the mortality correlate with these factors. A recent study of alcohol retail density showed a high correlation with these factors.  In other words, urban minority populations face a higher level of retail alcohol outlet density and exposure than white populations in urban or rural zip codes. The only difference from the study in reference 2 is that there are no clear measures of opioid exposure. 

This is an important study with a unique approach to the problem of progressive drug epidemics.  Mortality rate from overdoses is not the same as measuring the total drug exposure and resulting addiction but there is no clear way to determine that.  I would also not consider the heroin and fentanyl mortality rates to be independent of the original increase due to prescription opioids. My rationale is that there are very few people that start using either compound. Once an addiction to opioids starts there are progressively larger numbers of people each year competing for the pool of illicit opioids. They are looking for less expensive alternatives. Many are not risk averse and are consciously looking for more potent opioids. Although there is no data to support the progression from prescription opioids to fentanyl and heroin - clinical experience suggests it is the likely explanation and it could account for the mortality curve in Figure 1 as a single rather than multiple epidemics. 

These authors have come up with a unique contribution to the literature and I encourage anyone interested in the epidemiology of drug epidemics to read the full text of this paper.

George Dawson, MD, DFAPA 



References:

1:  Jalal H, Buchanich JM, Roberts MS, Balmert LC, Zhang K, Burke DS. Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016. Science. 2018 Sep 21;361(6408). pii: eaau1184. doi: 10.1126/science.aau1184. PubMed PMID: 30237320.

2: Berke EM, Tanski SE, Demidenko E, Alford-Teaster J, Shi X, Sargent JD. Alcohol retail density and demographic predictors of health disparities: a geographic analysis. Am J Public Health. 2010 Oct;100(10):1967-71. doi: 10.2105/AJPH.2009.170464. Epub 2010 Aug 19. PubMed PMID: 20724696.

Permission:

Both Figure 1 and Figure 2 above are used with permission from the American Academy for the Advancement of Science (AAAS) the copyright holders.  The figures are both from reference 1 above used with permission per the following license number  4441420359702  obtained on October 3, 2018.  The AAAS also requires the following notice based on this content:

"Readers may view, browse, and/or download material for temporary copying purposes only, provided these uses are for noncommercial personal purposes. Except as provided by law, this material may not be further reproduced, distributed, transmitted, modified, adapted, performed, displayed, published, or sold in whole or in part, without prior written permission from the publisher."

To All Of The Opioid Epidemic Deniers........

I encountered an absolutely stunning piece the other day about how there really was no opioid epidemic.  The author's various arguments all centered on the basic idea that law enforcement and other special interest groups spread the lie about opioid use being epidemic so that they could increase law enforcement measures and make it more difficult for chronic pain patients to get access to opioids.  There are a lot of these conspiracy theories going around. There are active posters on Twitter who continue to beat the drum that this is a heroin or fentanyl problem and not a problem with prescription opioids. The same group will suggest that the problem is now benzodiazepine prescriptions - maybe even gabapentinoids! They make the false claim that "anti-opioid zealots" want to stop opioids for chronic non-cancer pain, even if it means that some of those pain patients will commit suicide. They continue to post debunked information about how a trivial number of pain patients become addicted to opioids if they are properly prescribed.

Time for a lesson about the opioid epidemic and how it evolved from the land of 10,000 lakes - my home state of Minnesota.  The graphics I am posting here are all from the Minnesota Department of Health and the Minnesota Department of Human Services.  In some cases the opioid involved overdose mortality is broken down into specific categories and in other cases it is just an aggregate number.  The first graphics I am going to post is on the epidemiology of admissions for substance use treatment from two time intervals for comparison.

These maps are county by county density plots of the rate of admissions from a particular county comparing 2007 to 2017.  There are certainly limitations using administrative data but on the other hand it is the only data available and I would not be surprised if there was not some reporting obligation by licensed treatment programs to the state.  The most significant limitation on admissions data is that services in the US are rationed and there are never enough openings or finances to treat the people who need it.  Treatment programs also open and close. There is the question about whether all admissions are captured.

Given those limitations it is clear that the rate of admissions form Minnesota counties of residents being being treated for heroin use, methamphetamine use and intravenous drug use (IVDU) have all increased significantly from 2007 to 2017. In fact, the total number of IVDU admitted in 2017 was about the same for both heroin (N=5148) and methamphetamine (4843) users.  By comparison, in 2007 the number for IVDU were about 20% of the current numbers with heroin admissions at 1008 and methamphetamine admissions at 798.  In a separate report speedballing or the injection of methamphetamine and heroin is discussed but there are no numbers given on people who are using both.

The first lesson from admissions data is that the total number of residents using this compounds per county and the rate of use per county are both increasing. The geography of the spread is also of interest.  Minnesota has 54 counties and only 7 are considered metropolitan or urban counties.  The rest are considered rural.  Large blocks of these rural counties have increasing numbers of residents being treated for heroin, methamphetamine, and IVDU.  To me that is an epidemic.

 Additional data looking at the epidemic in Minnesota comes from reference 2.  It is interesting because it is a direct comparison of deaths occurring in rural versus metro or urban counties.  It also looks at the types of drugs involved in the overdoses.

As can be seen in the above graphs, opioid and heroin overdoses both increased over the 16 years of the study period. In the Metro sample, the baseline rate of opioid overdose deaths was 43 Metro and 11 Greater Minnesota in 2000 and by 2016 this had increase to 256 and 138 respectively.  In the case of heroin overdose deaths the baseline rate was 1 Metro and 1 Greater Minnesota in 2000 and by 2016 the increases were to 110 and 40 respectively.  The rate of increase in opioid and heroin deaths in Greater Minnesota may have been impacted by the greater rate of increase in stimulant use and associated deaths.  This may imply greater availability of stimulants across a wider population area than opioids - but overdose deaths is an obvious problems for all of the compounds listed on these graphs.  According to my arithmetic that is a 9 fold increase in the death rate due to opioid and heroin overdoses over 16 years.

The final consideration is how is it that so many people started using heroin and fentanyl?  Many of the epidemic deniers seem to be suggesting that it just happened that way.  It was totally unrelated to opioid prescriptions.  If a clinician like me tells them that I have talked to hundreds of opioid users and I have heard initial use of heroin from exactly one person - they suggest that I don't know what I am talking about.  That is where this compelling graphic about opioid prescriptions comes in showing about an 8-fold increase in opioid prescriptions in the USA over about the last two decades. It would place opioid overdose deaths as about the 13th leading causes of death in the state.  Once an addiction starts, the economics of drug use is that most people can get heroin for considerably less than they can buy prescription opioids on the street.  That and the general characteristics of addiction lead to higher risk use of intravenous heroin and a greater potential for overdose.

Even though every data set has it's limitations, the alternate hypotheses by the epidemic deniers need to be considered as alternate explanations.  Conspiracy theories about people scheming to prevent the treatment of chronic pain and the "war on drugs" don't make any sense. If either explanation were true it would have to explain the explosion in opioid prescriptions in the 21st century and everything that unfolded since.

It does not.

The only reasonable public policy must stop these overdoses and explode the associated myth that excessive opioid prescribing is necessary for the treatment of chronic non-cancer pain.



George Dawson, MD, DFAPA


References:

1:  DAANES SUD Detox and Admission Trends CY1995-CY2017.  Minnesota Department of Human Services, 2018.

2:  Drug Overdose Deaths among Minnesota Residents 2000-2016.  Minnesota Department of Health Injury and Violence Prevention Section, 2018. Link


Graphics:

All graphics are from public documents from the Minnesota Department of Health and Minnesota Department of Human Services.

The Whitening of the Opioid Epidemic....

I was reading the most recent copy of the Psychiatric News (May 4, 2018) when a story jumped off the page at me.  It was called "How the Opioid Addiction Crisis Was Rendered 'White'.   I knew I had to post about it here because it contains several inaccuracies that typically occur when racial explanations are used to look into any complex phenomenon.

The article is about positions espoused by Helena Hansen, MD, PhD and in fairness it was not written by her.  There is no guarantee that she might consider these accurate depictions of her positions.  The article starts out discussing a 2015 PNAS article on mortality in white middle aged Americans (1) and what the authors termed "deaths of despair" claiming that the new opioid crisis affects these people "linked with social and economic causes: decreasing wages, disappearing jobs, and a diminishing standard of living."  In the same paragraph, the author points out that rate of increase of opioid related deaths is occurring in 55- 64 year old African Americans (see the recent respective slopes in the top 2 graphs used in the article).  For completeness, I suggest going through this data visualization and generating graphs for all of the age ranges, looking at absolute rates and the rate of increase, and comparing those generated graphs to the total deaths bar graph above it.

Dr. Hansen spells out a selective marketing strategy of opioids to white Americans - specifically selling them OxyContin as an opioid painkiller with minimal addictive properties in the 1990s.  She said that was followed up with selling white Americans buprenorphine as  a treatment for addiction.  She describes this as the "whitening" of a new class of opioids "against a backdrop of a long history in which heroin and other drugs of abuse were similarly "racialized" as the substances of choice among blacks and other minorities...."  The racializiation was accompanied with "sinister criminal imagery that ignored the socioeconomic circumstances that had always contributed to addiction in minority communities."

She suggests this racialization or whitening of the opioid epidemic was made possible by:

1.  Deliberate ethnic marketing by Big Pharma.
2.  The pharmaceutical "magic bullet" approach or buprenorphine as a solution to the opioid problem obscuring psychosocial and economic factors.
3.  A health care system that does not make psychosocial treatments equally accessible by "geography, class, or race".

She goes on to point out that the distribution of methadone versus buprenorphine has an unequal distribution with methadone being more inconvenient and distributed primarily in inner city neighborhoods.  Buprenorphine on the other hand is easier to take and is distributed primarily in the suburbs and is more easily available to the white middle class.

She brings up a familiar refrain that promoting addiction as a brain disease devoid of environmental or psychosocial context that "anyone" can get - is really code for "anyone" = "white".  She suggests that white opioid crisis has stimulated discussion of of economic revitalization for the white victims of addiction while the black victims were criminalized.  She concludes that addiction is rooted in "social problems mediated by mental illness" and therefore we need psychiatrists to address this problem.

As an addiction psychiatrist I have addressed all of these themes on this blog in the past.  I can make it as straightforward as possible.   All of the social, economic, and psychosocial explanations of addiction are highly flawed simply because the vast majority of Americans laboring under those conditions do not become addicted.  As far as I  can tell economic revitalization is political rhetoric, especially in the current circumstances where what the government will actually do to address the opioid crisis remains unclear. 

There are two critical variables for addiction.  The first is biology.  There are strong genetic components that correlate with addiction as well as some epigenetic components.  Race is not a factor.  On that same spectrum, genetics determine that some people are protected against addiction by their biologically determined reactions to addictive drugs and alcohol.  This is not speculation on my part it is a known historical fact and scientific fact.  No matter who you are or what your race is - you need this biological disposition to addiction or it probably is not going to happen.

The second variable comes down to exposure.  If there is no exposure of addiction prone individuals to the addicting drug there is no addiction.  That is where Dr. Hansen is partially right.  When Big Pharma targeted physicians to prescribe opioids for trivial pain and maintenance opioids for chronic noncancer pain that brought opioids to a much larger group of people, basically non-metropolitan whites who started to die in rural areas of opioid overdoses.  And it was much more than opioids.

The example I use in my lectures is a teenager in rural northern Minnesota in the 1970s versus today.  Let's say he knows his grandfather died of alcoholic cirrhosis and his father is an alcoholic.  What would he need to do in order to avoid being an alcoholic or addict in the 1970s versus today?  In other words if we assume his genetic make-up is the same and he inherited the family predisposition to alcohol misuse - what does he have to avoid?

In the 1970s there were basically three things: alcohol, tobacco, and cannabis.  In some areas of the country there was an amphetamine epidemic but that had not reached the northern frontiers of the US.  How about in 2018?  Today he has to avoid everything - opioids, alcohol, tobacco, cannabis, synthetic cannabinoids, amphetamine, methamphetamine, and everything he can acquire over the Internet.  We have gone from a country where rural (and white) Americans were relatively sheltered from all of these addictive compounds to where they are widespread and easily accessed.  So easy in fact that you can get many of them (opioids, amphetamines, benzodiazepines) directly from your physicians office.

I disagree with Dr. Hansen's basic theory of this opioid epidemic and how it was "whitened."  This is not a racial issue at all.  As I have been telling my students for nearly a decade now - "Until recently - why was a kid in northern Minnesota relatively protected against opioid addiction relative to a kid in the inner city?"

The answer is that kid in Minnesota - until recently - did not have to walk past any drug dealers on the way to school.

Now they do and the only relevant equation is biological predisposition + exposure = addiction.  That same simple equation is also the most compelling argument against legalization of addictive drugs because by definition it would mean a larger percentage of addictions with increasing exposure.

Men discriminate based on arbitrary definitions of race and class.

Biology does not. That is why anyone white or black can develop an addiction.



George Dawson, MD, DFAPA



Reference:

1:  Case A, Deaton C. Rising midlife morbidity and mortality, US whites.  Proceedings of the National Academy of Sciences Dec 2015, 112 (49) 15078-15083; DOI:10.1073/pnas.1518393112

2:  Moran M.  How the Opioid Addiction Crisis Was Rendered White.  Psychiatric News, May 4, 2018, pages 19 and 23.

3:  Greene, Eddie L.Thomas, Charles R. et al.  Minority Health and Disparities-Related Issues: Part I
Medical Clinics of North America 2005, Volume 89 , Issue 4 , xi - xii

4:  Greene, Eddie L.Thomas, Charles R. et al.  Minority Health and Disparities-Related Issues: Part II
Medical Clinics of North America 2005 , Volume 89 , Issue 5 , xi - xii


Graphics Credit:

1:  National Center for Health Statistics - Drug Poisoning Mortality in the United States, 1999-2016 https://www.cdc.gov/nchs/data-visualization/drug-poisoning-mortality/



Supplementary (too tedious for the post).

Dr. Hansen	Dr. Dawson
Deliberate targeting of white people by Big Pharma marketing	Influence was at the physician and institutional level.  Increased access at many levels increased exposure to all Americans. Goal of the pharmaceutical industry is to develop “blockbuster” drugs by marketing and selling to as many physicians and patients as possible.
The pharmaceutical "magic bullet" approach or buprenorphine as a solution to the opioid problem obscuring psychosocial and economic factors.	If it was marketed that way – it was a poor job considering the number of overdoses that could have been prevented since it was released in 2002.  Even today there is widespread reluctance to prescribe it and use it and large social media groups advocating to not use it or taper off it. It is prescribed without considering the race of the patient.  In healthcare systems, a focus on a medication is frequently a way to not provide necessary services for anyone.  The obvious example is closing state mental hospitals and focusing on the success of chlorpromazine.
A health care system that does not make psychosocial treatments equally accessible by "geography, class, or race".	The problems with racial and class disparities in care have been widely known and occurred long before the current opioid epidemic (see ref 3 and 4).  Government sanctioned managed care system has been rationing mental health and addiction care for 30 years for corporate profitability.  Despite continuous discussion of the epidemic there is little evidence that the infrastructure or service for treating addiction has improved in any way.
No broader cultural theory.	Increased cultural permissiveness for drug use as evidence by widespread legalization of cannabis and the promotion of addictive drugs as therapeutic agents can increase the likelihood of illicit use.
Distribution of methadone clinics versus Suboxone prescribers	Suboxone is clearly more convenient but access to prescribers is very limited.  Suboxone patients often have to travel as far as they would have to get to a methadone clinic and then see a provider who does not accept health insurance and charges ala carte fees for service.  A segment of Suboxone users may do better on methadone.
Medical definition of addiction as a neurobiological disease that anyone can get was invented for white people.	Clearly applies to everyone unless you believe that there are some racial characteristics to suggest that one race is more susceptible than another.  As is the case with the majority of human illnesses I don’t believe there are any susceptibilities to acquired illness based on race.
Mental illness is a product of socioeconomic circumstances and a precursor to addiction.	In genetic studies mental illness co-aggregates with addictive disorders, genetic susceptibility to one increases susceptibility to the other.

Latest From MMWR On Opioid Prescribing In the USA

The CDC continues to do outstanding work in providing useful metrics for monitoring the current opioid epidemic.  The latest edition of the Morbidity and Mortality Weekly Report is no exception.  In this analysis the authors look at a database representing 88% of the opioid prescriptions through retail pharmacies in the USA over the period 2006 to 2015.  Buprenorphine products used for medication assisted treatment of opioid use disorder and other preparations containing opioids for non- pain treatment like cough syrups were not included in the total amounts.

They calculated various metrics of interest from the data including the milligram morphine equivalent (MME) per capita and prescribing rates (per 100 persons) for overall rates, high dose rates, and prescribing rates by days of supply given (<30 days or ≥ 30 days).  They also looked at county by county rates over the time period studied.  

Before I look at the result,  I will digress a bit on the MME measure.  There are standard conversion charts like this one used by the CDC that allows for conversion of a standard dose of an opioid into a MME.  A few examples will illustrate the utility of this conversion.  Suppose a person is prescribed oxycodone and acetaminophen tablets.  Most of them contain 5 mg oxycodone + 300 mg acetaminophen.  If the prescription says to take one tablet 4 times a day of needed for pain that is 20 mg oxycodone total or 20 mg x 1.5 (conversion factor) = 35 MME.  Using the same example for hydrocodone (5 mg hydrocodone + 300 mg acetaminophen) yields 20 mg x 1 (conversion factor) = 20 MME. That means that roughly either of these prescriptions taken for one month, once a year gets to the per capita MME of 640.

In addiction practice it is common to see people who are taking 120 to 240 mg/day of oxycodone per day.  Doing the conversions yields a range of 180-360 MME.  There is no good conversion from heroin to MME due to varied methodologies of use and very short half-life.  With methadone the problem is long half-life and tolerance leading the conversion table to yield higher conversion factors at higher dose.  With the calculations it was observed that the MME per capita peaked in 2010 at 782 MME and then decreased to 640 MME per capita in 2015.  Both numbers are significantly higher than the MME per capita in the US in 1999 when it was 180 MME.   Additional graphics of the other metrics from this article can be found in the tables below.

   A scan of the above graphics starting from the top left shows that the rate of opioid prescribing including high dose prescribing (> 90 MME/day) has decreased beginning in about 2010.  The rate by number of days supply has increased slightly as has the number of days supply per prescription.  The overall MME per prescription has decreased.  The authors quote studies that show that patients are at risk for continued opioid use if they take them for more than 5 days and that once a person has been taking opioids for 90 days they are not likely to discontinue them.  There is also the CDC infographic of prescription opioids as a gateway drug.  People addicted to prescription painkillers are 40 times more likely to be addicted to heroin.

In the county by county assessment there were more decreased in overall prescribing rate (46.5%) and MME per prescription (49.6%) than stable or increased rates.  The high dose prescribing rates dropped the most (86.5%).  It is likely that guidelines describing the higher risk of high dose therapy affect these rates than the recognition of opioid use disorders in chronic pain patients.  There was a significant increase in the average day per prescription in the county by county analysis (73.5%).

The authors also looked at a complex stepwise multivariable linear regression looking at numerous demographic variables and concluded that several variables accounted for higher amounts of opioids being prescribed including ( lower educational attainment, higher unemployment, more physicians and dentists per capita, higher prevalence of conditions associated with chronic pain (diabetes mellitus, arthritis, disability), higher  suicide rates, and higher rates of uninsured and Medicaid enrollment.  These variables accounted for 32% of the opioids prescribed at the country level.

The study has the expected limitations of a large retrospective database study.  There are signs that that physician education and some regulatory action may be  having an influence in opioid prescribing.  Any reduction in the populations exposure to opioids would be expected to have some impact, but as of 2015 there were an estimated 2 million prescription opioid addicts (2).  The recent transition from prescription opioids to heroin and some street products containing fentanyl and carfentanil has been responsible for an increase in opioid overdoses despite the change in prescribing patterns.  Although the total opioid MME per capita has decreased it is still about 3 times higher than it was in 1999 - the year before the current epidemics inflection point.  Proponents of liberal opioid prescribing might say (and have said) that the prescribing of opioids for chronic noncancer pain in the years leading up to 1999 was too stringent and deprived patients of needed pain relief.  My experience with addiction suggests otherwise.

The risks of addiction with opioids is great.  A current underemphasized area is primary prevention or not exposing young adults to opioids.  The take home message from this paper is that secondary prevention may have an impact but at this point it is not clear cut.  One thing is certain and that is the CDC does great work getting this data out and freely available to all interested physicians and patients in the world.

It will be a solid record of how the opioid epidemic evolved and hopefully at some point - resolved.          


George Dawson, MD, DFAPA





References:

1: Guy GP Jr, Zhang K, Bohm MK, Losby J, Lewis B, Young R, Murphy LB, Dowell D.Vital Signs: Changes in Opioid Prescribing in the United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017 Jul 7;66(26):697-704. doi: 10.15585/mmwr.mm6626a4. PubMed PMID: 28683056.

2: Substance Abuse and Mental Health Services Administration. Prescription drug use and misuse in the United States: results from the 2015 National Survey on Drug Use and Health. Rockville, MD: Substance Abuse and Mental Health Services Administration; 2016. https://www.samhsa.gov/data/sites/default/files/NSDUH-FFR2-2015/NSDUH-FFR2-2015.htm

Attribution: Both of the graphics in this post are from reference 1 above.  Both are used per the user agreement for the MMWR that states this information is in the  public domain.

Enhancing The Volkow-Collins Approach To The Opioid Epidemic

Nora Volkow, MD - Director of the National Institute on Drug Abuse and Francis S. Collins, MD, PhD - Director of the National Institutes of Health co-authored a paper on the role of science in the current opioid crisis.  Full text of the article is available free online from the New England Journal of Medicine at the reference given below.  In the article the authors review the scientific interventions at three levels of care in treating opioid addiction and use, treating and preventing overdoses, and the treatment of chronic pain.  The treatment of chronic non-cancer pain (CNCP) with opioids can be realistically viewed as the precipitant of this epidemic.  The brief 4 page review is a good rapid review of the science behind these interventions.  The level of cooperation between NIDA and NIH with private industry may surprise a few people but as the authors point out -  the level of mortality with the current epidemic needs to be approached with urgency at all levels.

At the level of opioid overdose prevention and reversal - more potent and long lasting opioid antagonists are being developed to counter exposure to fentanyl and carfentanil appearing at an increasing rate on the street.  Narcan Nasal Spray is probably the most effective and practical outcome of the industry-NIDA partnership.  A wearable device that can detect signals of an impending overdose and administer a μ-opioid receptor antagonist is mentioned.  At the level of addiction treatment methadone, buprenorphine, and extended-release naltrexone are all mentioned as current treatments for opioid use disorder.  Access to providers is discussed as a limiting factor.  vaccines and novel receptor approaches are discussed as potentially new pharmacological approaches to the problem.  New approaches to chronic pain are discussed in greater detail.  Cooperation between the NIH and industry is emphasized again in terms of getting these approaches to market and clinical use.  In the concluding section - the emphasis on NIH-industry partnerships is a central theme.  The argument makes imminent sense, but after two decades of rancorous debate about the effects of pharmaceutical company pizza on prescribing - this level of access to the highest level of taxpayer funded research is somewhat stunning.

But what else might be immediately useful?  I can concentrate just on buprenorphine and come up with a couple.  Anyone working with this compound and people who are addicted to opioids routinely encounters problems with its use.  It is common to treat people who still have withdrawal symptoms and cravings on the  recommended doses and remain at high risk for relapse even after being treated with what is described as one of the best current therapies.  Taking a look at the recommended dose range from the package insert:

The upper limit of the recommended dose is 24mg/6mg buprenorphine/naloxone per day for SUBOXONE. The reported lack of significant increase in brain mu‐receptor occupancy between doses of 16 mg and 32 mg implies that there should be little difference in clinical effectiveness at doses between 16 mg and 24 mg in most patients. When a patient expresses a need for a higher dose, consider the possible causes (e.g., environmental stressors or psychosocial issues that increase cravings or possible drug interactions). Before increasing the patient’s dose, explore other alternatives. Also consider the possibility that the patient may be exaggerating symptoms to obtain additional medication for diversion. (p 34-35).

And:

The recommended target dose is 16 mg buprenorphine/4 mg naloxone per day. Clinical studies have shown that this is a clinically effective dose. Although lower doses may be effective in some patients, for most patients, a 16 mg dose should alleviate withdrawal symptoms and block or attenuate the effects of other opioid agonists for at least 24 hours. (p. 34)

In clinical practice there is a wide range of effects to buprenorphine doses.  The FDA approved considerations show the subjectivity involved in adjusting the dose.  But that is even an understatement.  There needs to be a much greater investigation of the causes of continued craving and withdrawal symptoms when the patient is taking a recommended dose of buprenorphine.  This may be a genetically determined phenomenon either at the pharmacokinetic or pharmacodynamic level.  That is only partially accounted for by drug interactions.

Investigation of withdrawal symptoms and continued craving is more than just a passing concern.  It potentially determines who will be able to remain on maintenance therapy and stay off of heroin.  It is important because a significant number of these patients are being actively treated for psychiatric disorders with antidepressants, anxiolytics, atypical  antipsychotics and mood stabilizers.  How much of that medication use is due to inadequate treatment with buprenorphine and the common symptoms of insomnia, anxiety, and depression associated with opioid withdrawal.  These are all very complex clinical situations.  Many of these patients have a life long history of stress intolerance and there can be a reluctance on the part of clinicians especially if they have no mental health training to explore and treat those problems.  Once the patient has been indoctrinated into the idea that a maintenance medication is going to help them stay off heroin - it is a difficult transition to now say that all of these other factors are now important and need to be addressed.  That is especially true when some of the existing buprenorphine studies minimize counseling or are publicly presented as "counseling adds nothing to the results obtained with buprenorphine."  Finally, there is a large social media movement of people who want to stop buprenorphine and are warning others about it.  What is behind this widespread dissatisfaction and what needs to be done to resolve it?  The overall impression that all of the issues in this paragraph leaves is that buprenorphine is another heavily hyped medication that does not live up to the claims.  All of these areas could use much clearer input from NIDA through additional scientific investigation.

Additional studies on drug interactions with buprenorphine are critically needed.  I use a standard commercially available drug interaction software package.  Any time I enter a psychiatric medication I get a warning to consider to modify therapy and a list of 230 potential drug-drug pharmacodynamic interactions at the CNS level.  Since there is a high prevalence of patients on maintenance psychiatric medications this represents a deterrent to some physicians, especially if they are not psychiatrists and they are in a state with an unfavorable malpractice environment.

The next issue is determining who is susceptible to opioid overuse and dependence.  In my mind the phenotype is very clear.  The person who takes the first opioid tells me that they either "fall in love with it" or they experienced an intense euphoric and almost hypomanic effect.  They felt transformed by the medication into a person that they had always wanted to be.  Side effects are modestly effective deterrents, but I have been told that side effects and a complete lack of analgesia are acceptable in order to get the intense, euphoric high.  How can these people be identified?  The authors discuss biomarkers for pain and pain relief - but the single-most important biomarker would identify this high risk group of patients for addiction.  There are currently commercial databases out there that poll their members on various traits and symptoms.  Can NIH or NIDA design the polling questions and look for markers in these existing databases?

Even before that marker is identified, is there a simple strategy that could be used in clinical practice? Could a clinician tell a patient to self monitor for the intense euphoria and report back to the physician as soon as possible if it occurs?  Could the patient be told to just dispose of the pills by bringing them in to the pharmacy if euphoria and thoughts of dose escalation occur?

These are some thoughts that come to mind that might be immediately useful.  They would address both the limitations of medication assisted treatment and identifying the at-risk population for primary prevention of opioid use problems.                
    

     
George Dawson, MD, DFAPA

1: Volkow ND, Collins FS. The Role of Science in Addressing the Opioid Crisis. N Engl J Med. 2017 May 31. doi: 10.1056/NEJMsr1706626. [Epub ahead of print] PubMed PMID: 28564549.

Lawyers, Libertarians, and Journalists On the Opioid Epidemic

It was a perfect confluence of events today.  At one point or another I heard or read about somebody's theory of why there was an opioid epidemic, deaths from drug use, and who was to blame.  Although some of the discussants were quite heated they all had one thing in common - they were all dead wrong.

Let me start with the lead story - the Attorney General of the State of Ohio suing drug manufacturers for the massive opioid problem in that state.  I say massive because there are an estimated 200,000 opioid users in the state and an associated mortality.  If you listen to the story (1) many local coroners and morgues are overwhelmed by the body count.  I heard the story on Minnesota Public Radio on the drive home tonight.  Ohio Attorney General Mike DeWine is suing Purdue Pharma, Johnson & Johnson, Teva Pharmaceuticals, Endo Health Solutions and Allergan for their role in the opioid epidemic.  Apparently the state of Mississippi filed the first law suit in the area.  The AG alleges that these companies basically convinced physicians through their questionable marketing efforts that these drugs were much safer than they really were and more effective for the conditions that they were supposed to treat.  Robert Siegel the reporter made an attempt to blame physicians instead and asked why they were not named in the law suit.  The AG's position was that the culture of medicine was affected by the false promotion and that it will take a while to change things around.  See the press release here for the exact position of the AG.  A copy of the entire complaint by the AG is available here.

The second story (2) came to my attention on my Facebook feed.  This was a case of  Ross Ulbricht - who was apparently convicted and sentenced to life in prison based on operating a darknet market that he created called Silk Road.  The conviction was apparently for money laundering, conspiracy to traffic narcotics, and computer hacking.  My interest in this case has nothing to do with the charges, the defendant himself, the conviction or the sentencing but the reaction on various web sites about the case.  There is a consensus on some of these web sites that he was offering valuable service for adults who want to come together and freely exchange items that it might be difficult for them to exchange in other places.  The associated arguments are that competent mature adults should be able to do this, that any interest the state has in suppressing such activity is an inappropriate intrusion on individual rights, and that in fact a service like this was essentially competing against cartels and may put them out of business. Some suggested that there was a conspiracy between the state and cartels to put sites like this out of business.  

All of these arguments fall flat to an addiction psychiatrist like me.  They seriously underestimate the effect that an addiction has on the brain and conscious state of an addicted individual.  Imagine what it is like to get out of bed in the morning and the very first conscious thought is: "How can I score some dope today so that I can function?" At that stage you are no longer a competent adult able to weigh decisions and make them in your best interest.  All of your decisions are weighted in the direction of ongoing drug use and addiction.  That is true if you are on the darknet looking for drugs or standing on a street corner in Ohio.  That is true if you are sitting in a physician's office and telling them what you think they need to hear to enable them to prescribe you more opioids.

The second aspect of opioid addiction that is difficult to understand is the genetic predisposition to addiction.  There are still a lot of pop psychology theories about addiction being just a bad habit or a lack of moral character that seem to explain the differences between people with addiction and people without addictions.  The fact is a substantial part of the population is genetically vulnerable to addiction and it is just a matter of whether or not they are exposed to a highly addictive drug.  If I had to estimate, my best guess would be that number is at least 40% of the population.  By that I mean that 40% of the population will get an extremely euphorigenic response to opioids (whether or not they work for pain).  They will remember that response and if exposed to more opioids are much more likely to use them than not use them.

That is what makes it so hard to stop this epidemic.  Without those two basic features of addiction there is no unlimited demand for addictive medications from pharmaceutical companies.  There is no need to go to a part of town that a person would never typically travel in to purchase diverted prescription opioids or heroin.  There is no need to search out opioids or other addictive drugs on the Internet or the dark net.

Doctors don't get off the hook.  All physicians are taught about controlled substances and the schedule of controlled substances.  All physicians know that opioids are scheduled according to their addictive potential.  The problem is that most physicians do not know how to interact with people who have significant addictions, and even experts can be fooled.  Most physicians have an incredibly naive approach to addiction and how they can prevent it or approach it once it is established. The cultural norm that physicians help people by prescribing them medications, combined with the fact that physicians are trained to help people, creates a powerful force to continue to prescribe addictive pain medications.  The absence of competent detox facilities is another.  

Pharmaceutical companies, doctors, judges and prosecutors - the pro and anti-blame rhetoric around this issue is intense and unrelenting.   It is not any easier to stop the current opioid epidemic when lawyers, libertarians, and reporters are spreading the blame around to anyone or anything other than the real cause of the problem - the addiction itself.

Start there - treat it as a public health problem and start to make progress.


George Dawson, MD, DFAPA      


References:

1:  Ohio Sues Drug Companies Over Role In Creating Opioid Epidemic.  All Things Considered; may 31, 2017.  Transcript and audio clip.

2:  Brian Doherty.  Ross Ulbricht Loses His Appeal Over Conviction and Sentencing in Silk Road Case.  Hit and Run Blog.  Reason.com  May 31, 2017.


Supplementary:

A reminder about the Ross Ulbricht case.  I am not focused on the case per se or the War on Drugs.  I am solely focused on the argument that anything can be openly traded on a market between consenting adults.  I do not dispute the argument that the sentence was excessive or any other arguments for that matter.

Minnesota Street Drug Bulletin - Carfentanil

Opioids morphine (upper left) and hydrocodone (lower left) and synthetic opioids fentanyl (upper right) and carfentanil (lower right)

I don't know how widely known the issue with potent opioids  on the street is - but I am concerned that the information is not getting out to the people who need to hear it.  There are warnings that are read mostly by health care providers.  There are politicians talking about tougher penalties and legal approaches to solving the problem.  Like many people, I don't believe that the War on Drugs has been very successful.  At the same time, there are not many readily available options, there is a historical precedent for control of narcotics, and we will never know what the outcome might have been without legal action against illicit drugs.  I don't think that a failed War on Drugs means that there should be mass legalization of drugs.  The reason is obvious.  We are in the middle of an opioid epidemic that has been initiated and sustained by legal prescription opioids.  This epidemic says more about the nature of addiction than legal deterrents.  It is very clear that people with addictions will not hesitate to obtain what once were legally prescribed medications and use them.  It is very clear that designating legal addictive drugs does not reduce the black market for highly addictive drugs or create more tax revenues for governments - both common arguments for drug legalization.  All of these abstract arguments don't reflect what happens on the street.

I have personally talked with hundreds of opioid addicts over the course of my career.  In the 1980s and 1990s - there was a small population of users largely due to limited access.  Heroin and illicit opioid prices were relatively high and the barriers to use were also high.  Widespread exposure to opioids in high school was unheard of.  Most of the people I treated were part of a small, relatively fixed population of heroin users and some were on methadone maintenance.  That has all drastically changed in the last 15 years.

Now it is common for me to talk with young people in their 20s who were exposed to opioids when they got opioid prescriptions for injuries that used to be treated with ibuprofen or acetaminophen.  In some cases their peers in high school suggested they should try taking hydrocodone or oxycodone to get high.  In many cases those drugs were scavenged from unused medications in the family medicine cabinet.  Like many people in their teens and early 20s there is a cultural movement among users that they have a special body of knowledge about these drugs.  That reinforces drug taking behavior and keeps them in contact with people who are actively using and supplying these drugs.  In some cases it leads to mistakes in how the drugs are taken and what they are mixed with.  Drug users often have illusory relationships with drug dealers that makes it seem like these dealers care more about them than their friends and family do.  With continued and progressive use, opioid users might not notice how their judgment is more and more impaired - often to the point that they don't care if they die in the process of trying to get high.  To be clear, these people will deny any intent to harm themselves but get to a situation where they are using a questionable amount of drugs and realize it could be a problem but at that point they no longer care.  Heroin overdoses and deaths are common in small towns across America.  That was unheard of in the 20th century.

Against that backdrop - carfentanil has hit the streets in Minnesota.  Carfentanil is an extremely potent opioid that was never intended for therapeutic use in humans.  It is a large animal veterinary tranquilizer.  Its toxicity in humans is not disputed.  The most significant incident was the use of a gas that probably contained carfentanil in a hostage situation at the Dubrovka theatre in Moscow.  There were 40 Chechen rebels holding 912 hostages.  Russian security forces pumped in a gas that killed all of the rebels and 130 hostages.  The gas was described as a sleeping gas and later fentanyl.  Recent research suggests that the gas was a combination of carfentanil and remifentanil.  Some authors suggest that this was an anesthetic, but I have not been able to find any clinical application of this opioid in humans.  Potent opioids like fentanyl are used as anesthetic agents as well as pain medications.  

One of the ways that drug dealers amplify their profits is by taking a relatively inexpensive but potent product and diluting it down and selling the diluted product.  I have a previous post that shows how drug dealers can take $3800 of the synthetic cannabinoid AMB-FUBINACA and produce about a half million dollars worth of product containing about 64 mg of the original compound sprayed over shredded plant material.  I am not about to post how carfentanil can be diluted.  There are media reports that talk about how much more potent the drug is relative to both fentanyl and morphine.  Anyone trying to guess about how the raw drug can be cut is making a big mistake.  The amount of drug that can lead to a lethal overdose is so small that any non-uniform distribution in a powder or tablet can result in a lethal overdose.  The drug is so potent that even touching the powder can result in an overdose and health care workers have been warned not to touch the powder for that reason.

The problem is that carfentanil is being sold as a number of different products on the street. People are being given carfentanil as powders and tablets and being told that it is heroin, oxycodone, hydrocodone, and even benzodiazepines. This is an extremely dangerous practice and several Minnesotans have already died because of it.

Don't make the mistake of even trying opioids to get high. If you are currently addicted to opioids go to detox and get treatment. Don't make the mistake that you have another 5 or 10 years to get clean.  If you need to take opioids, get Medication Assisted Treatment with buprenorphine or methadone, rather than continuing to use what is available on the street.  With FDA approved medications used under a physician's supervision - you know exactly what you are getting.  The Minnesota Department of Health recommends education in overdose prevention and naloxone administration.

I can tell you that you can't trust what you are buying on the street.

But deep down you already know that.  Carfentanil is just another clear-cut example.



George Dawson, MD, DFAPA        


References:

1:  Influx of Fentanyl-laced Counterfeit Pills and Toxic Fentanyl-related Compounds Further Increases Risk of Fentanyl-related Overdose and Fatalities.

2:  Health Advisory: Drug Overdose Deaths Linked to Carfentanil Minnesota Department of Health Mar 31, 2017 12:00 CDT

3:  Carfentanil Medline references


Attribution:

All molecules at the top of this post were downloaded from PubChem and are in the public domain.