Overprescribing Bubble Diagram Explained

This post is intended to explain the bubble diagram that I used in the last post about overprescribing.  It focuses on the physician rather than a number of extraneous factors that are the speculative causes of overprescribing that do not make sense.  The literature on this is spotty.  There are a few references that include diagrams and purported mechanisms of overprescribing.  Before I consider those, I want to put down what I know.  The bubble by bubble explanation follows starting at the top left of the diagram - but each bubble is easily identifiable:

1.  Unconscious Motivations:  This is one of the areas that I consider to be the primary cause.  It encompasses both unconscious and preconscious causes.  The best way to look at it is with a few examples.  Overidentification with the patient seems to be a fairly common cause.  For example, a physician might have attention deficit hyperactivity disorder and realize that with treatment they were able to do much better academically.  They have a lower threshold for seeing the problem in others based on their experience.  In their medical group they are seeing many more ADHD patients than their colleagues and prescribing far more stimulant medications.  That is really a special case of the physician wanting to do something positive for the patient.  That can lead to a reduced awareness of other causes such as substance use or a person seeking cognitive enhancement and drive the prescription process.  The wish to be appreciated and have a positive relationship with the patient is another issue.  Consider the patient in clinic an uncomplicated upper respiratory infection.  Near the end of the clinical encounter, the patient senses that there will be no prescription and starts to get annoyed.  The patient talks about his or her past experience and how an antibiotic always seems to clear up their cold symptoms.  They put the physician on the defensive about the antibiotic issue and rather than argue with the patient - the physician hands over the prescription.  All of these scenarios and more reflect unconscious factors involved in prescribing and as far as I can tell this important area is untouched in the overprescribing literature.

2.  Medical knowledge:  This occurs at two levels.  The first is just the rote declarative knowledge that involves the memorization of factual knowledge about medications.  This seems like a fairly basic skill, but the amount of information we are talking about is encyclopedic.  To illustrate this all one has to do is to pull up recent FDA approved package inserts for drugs that are advertised on television.  All of the pharmacological details are presented in a neutral and highly detailed manner.  There is some prioritization in terms of  contraindications and precautions, but that is still a lot to memorize.  Experienced clinicians will still read these documents repeatedly and use summary references until they gain enough experience with the medication.  The second level is the patterns that become familiar when using the drug.  For example, after I have prescribed a drug enough times, I can tell anyone taking it what my experience with the medication is and what the experience of my patients has been.  That information is really not available anywhere else and it also can lead directly to additional testing.

3.  External validation:  The best objective source of external validation is prescribing medications according to the FDA approved indications and as instructed in those documents.  Off label prescriptions should be backed up by some data. I typically research all off label prescribing by doing Medline searches and looking for actual clinical trials looking at that application.  Example would include looking at the use of gabapentin for chronic pain and treatment of alcohol withdrawal.  Even though there are no FDA approved applications, there is ample evidence about how to use these medications, including very specific dosing recommendations.

4.  Conservative prescribing bias: My goal has always been to treat the primary problem but also eliminate or minimize problems related to the medication.  That is not the goal of some physicians.  I heard an expert in the treatment of anxiety disorders suggesting that patients needed to be treated to the point of toxicity with a medication and then the medication could be reduced.  That is not necessary as far as I can tell.  Another issue here is exceeding the FDA approved range for medication use.  Quality markers for dose range and multiple medications from the same class are nothing new and date back at least 20 years. This information is also part of informed consent and the patient should hear about it and other options at the time the change is being considered.  I have spent a lot of time correcting unnecessary high doses and polypharmacy, generally to the benefit of the patient involved.

5.  Social context:  A group of interested physicians who keep up on the research and analyze prescribing patterns is a robust safeguard against overprescribing. There are some settings for example where benzodiazepines or benzodiazepine related sleep medications are not prescribed in any circumstance.  Stimulant medications are used only by review with a colleague and the medical director and documentation on a signed form.  Such a review procedure is available to any group has utility in preventing variation in prescribing patterns and practice variation.  Practically every major clinic and hospital has a program that targets antibiotic overprescribing especially the overuse of expensive, toxic or antibiotics that are the last defense against bacteria with multiple drug resistance.  This social factor is a powerful safeguard against overprescribing.

6.   Physician as a source of information and teaching:   If the physician is in a position to teach patients about a medication they generally have a more nuanced knowledge about the medication.  They avoid stereotypes like: "When I see this problem I always prescribe this drug."  They are also aware of the likelihood of the patient recovering without the drug and the fact that any drug effect may be weak.  A classic example is low back pain in adults.  Patients generally lack knowledge about the importance of avoiding deconditioning and the need for ongoing physical therapy and back specific exercises.  They are generally surprised that conditioning provides a significant amount of pain relief.

These are a few brief examples about what can be done.  All of these dimensions occur in the context of political and regulatory influences.  For example, the FDA initiatives to approve potent opioid medications that are essentially not much different in terms of risk from current medications during an opioid epidemic.  Guidelines suggested by outside sources may not be very useful if there is insufficient evidence and the information is broadly disseminated to clinicians.  The bubbles listed on the diagram are potent factors in countering any trend that may lead to oversubscribing and they do not involve penalizing or threatening physicians - typical actions used by law enforcement or politicians that may have caused the problem in the first place.

The reader will note that I am not concerned about diagnostic proliferation.  I don't think that overprescribers do this based on the availability of new diagnoses.  I base this on my observations of the patterns that exist independently of new diagnoses and can provide a number of examples.  Physicians are trained to "do" something medical or surgical and over the course of my career that bias has not panned out in a number of areas.  Targeting that tendency will be more productive than complaining about pharmaceutical companies, diagnostic manuals, or guidelines especially when our major regulatory agency has the bias to get a drug out there for general use based on highly variable scientific evidence.  As recently noted the FDA can also ignore the recommendations of their own scientific committee.

In the end, the best assurance of adequate medical treatment and minimal risk from the treatment depends on the expertise and judgment of a physician.

George Dawson, MD, DFAPA  

Supplementary 1:  After staring at the diagram for a while I think I need to add a 7th Bubble that I would probably call "Heuristics".  It would focus on the cognitive and emotional biases that exist in prescribing.  For example,  everyone in their practice may have a person with an addiction who was subsequently able to take an addicting medication without relapsing to their primary addiction.  Is that a reason for making that a rule for prescribing?  There are a number of ways to look at potential biases in prescribing that can improve the evaluative structure of that process.

Some Arguments on Drug Tolerance and Prohibition

I have extensive experience treating people with alcohol and drug use problems.  I am always amazed at the lack of knowledge about addiction and alcoholism in the general public and how that impacts public policy.  As a result I occasionally get involved in public forums to argue a few points.  As a matter of disclosure I am thoroughly independent and vowed not to vote for any major party candidates a long time ago.  That doesn't prevent people from sending me heated e-mails accusing me of either being a Democrat or a Republican.  Of course you can also be attacked for being a independent and being too much of an elitist to not accept the fact that only major party candidates can be elected.  I have never found that to be a compelling argument.  My latest post to the quoted excerpt follows.  You can read the entire sequence of posts by clicking the link at the bottom.  There are obvious limitations to engaging in this exercise and that should be evident by reading the exchange right up to the last post where I get the expected shot for being a psychiatrist.  Tiresome isn't it?

“Come again...Politicians are pushing for legalization?  Politicians have been spewing the “war on drugs” “tough on crime” protecting the “fabric of society” bullshit for the last 40-plus years.”

Sorry – I try just to stay to the facts.  If you read the actual history of drug use in this country we swing from periods of prohibition to drug tolerance.  We are currently swinging into a period of drug tolerance and I fully expect to see drugs legalized in some way or another in most states.  So I really don’t have a stake in this fight either way.  So you can lighten up.  I am not “on your side” but I can predict with certainty that it will happen.  You can Google “politicians who support drug legalization” as well as I can.  As more of them get on board you will hear an escalation in rhetoric on how they will tax and control it.

You can put any type of spin on it you want – more freedom, freedom from the war on drugs, ability to generate more taxes, ability to treat any problem you might have with medical marijuana, you name it – history shows the outcome will be the same.  If you are still serious about legalizing heroin and coca like you previously stated that experiment has already been done and the outcome will be the same.  That experiment is being done right now with diverted legal opioids (the source of synthetic heroin) and according to the CDC we are in about year ten of an opioid epidemic that is killing more people in many states than motor vehicle accidents – about 15,000 people a year.  If you consider that the drugs typically called synthetic heroin on the street are usually pharmaceuticals with known safe doses, that also illustrates the nature of the problem.  If you think that nobody will be looking for synthetic marijuana if marijuana is legalized – I know that is false per my previous post.  No matter how free you are to smoke marijuana, there are very few employers I know of that will tolerate it at work and none if you are in a job where your decision making can lead to substantial liability. 

The problem with the “war on drugs” and excessive incarceration of people with drug charges in many ways parallels the excessive incarceration of the mentally ill because we have a health care system that is politically managed.  The politicians realized a long time ago that you can save health care costs by incarcerating the mentally ill instead of treating them in medical settings.  It may not have been a conscious decision up front but they have done little to stop it after it was clearly underway.  The three largest mental hospitals in the US right now are county jails.  Addicts in many cases are treated even more poorly if they are incarcerated because they do not get medically supervised detoxification and go through acute withdrawal.

In any “war” somebody has to be blamed and denied resources.  I prefer Musto’s analysis of the US tending to blame other countries for our drug problems:  “That analysis avoids the painful and awkward realization that the use of dangerous drugs may be an integral part of American society.”  That is reminiscent of Mexico’s Past President Vincente Fox pointing out that Mexico’s problem with cartel violence is fueled by America’s massive appetite for drugs supplying the money.  On that basis he was a proponent of the legalization and control of marijuana argument.  That doesn’t address the massive appetite for drugs problem.

The problem with the politics of addictive drugs is that people generally don’t know much about addiction.  There is a significant portion of the population that is vulnerable and the only thing it takes in increased availability for them to start having significant problems.

So good luck with the new temporary American dream of increased access to intoxicants and enjoy it while you can.  Depending on exactly what gets legalized – I would predict that would be the next 20 – 40 years.  That is the usual time it takes to complete a cycle.

Minnesota Politics and Issues Forum

George Dawson, MD, DFAPA

David F. Musto.  The American Disease: Origins of Narcotic Control.  Third Edition.  New York, Oxford University Press, 1999: p 298.  

Additional Clinical Note 1: A couple of graphs from my other blog that show alcohol use patterns over time are available on my other blog for the United States and the United Kingdom.  Graphs of opioid consumption over the past decade by the UN drug control agency shows a linear increase in consumption and production.

Additional Clinical Note 2:  If you had the patience to follow the political thread you probably notice the marijuana advocate trying to tell me that I was saying there was an epidemic of synthetic marijuana abuse that occurred with the legalization of marijuana.  My argument was simply that marijuana users if they are screened for THC at work will switch to synthetic marijuana in order to avoid positive toxicology screens and job loss.  Now in the February 5, 2014 edition of JAMA a report from the CDC it turns out that there was an "outbreak" of synthetic marijuana use in Colorado in August and September that involved about 200 people.  There was a similar outbreak in Georgia in August of 2013.  In addition  to the medical characteristics I would encourage the CDC to collect data on how many people were smoking marijuana to avoid toxicology testing and how many people were unable to stop smoking marijuana in order to achieve that same goal. I sent the CDC a note on how to refine their methodology. 

Supplementary Material Note 1:  My response from the CDC.

Why Has Suboxone Turned Into A Problem?

The short answer is that it is like very other drug and there was always the potential for a problem.  Any practicing physician realizes that when a drug is approved by the FDA for general release to the public there are all kinds of unintended consequences that are possible.  That is the basis of post marketing surveillance by the FDA.  There is invariably a lot of hype associated with the release of a drug, but as I have previously pointed out the FDAs approval process is not in place to guarantee a drug that is safe for everyone.  It is focused on a releasing a drug that is a potential tool for responsible practitioners.  That means any drug can potentially cause a small number of serious unexpected reactions (liver failure, cardiac arrhythmia)  that even the most experienced practitioners will not be able to predict.  There is also an implicit understanding that the practitioners prescribing the drug have a thorough understanding of its pharmacology, indications and contraindications.  Many practitioners advise against trying out a product that has just been released but that advice is tempered by the severity of individual circumstances and the hope of relief and also the general bias that new drugs are somehow better than the old ones.  That bias has been repeatedly disproven.

Suboxone prescribers have to take a special course in order to get a prescriber number in addition to their usual DEA number.  I took the Suboxone prescriber course about 7 years ago.  It was a total of 8 hours of lectures given in a convention center room in a hotel.  It was jointly sponsored by state medical association.  The morning sessions were largely a review of the pharmacology of the drug and the scope of the opioid addiction problem at the time.  The afternoon session focused on vignettes of patients with addictions of varying complexities and the exercise was to determine of Suboxone should be prescribed to that person and how the induction would be done.  That was the first suggestion that something was problematic.  There apparently were no contraindications to Suboxone.  The clear message was that it should be given to anyone with an opioid addiction no matter what their social circumstances or comorbid psychiatric diagnoses and addictions.  There was a definite implication that this was a drug that would revolutionize the treatment of opioid addiction.

 
Suboxone is a combination of buprenorphine and naloxone.  Buprenorphine is the active ingredient in terms of treating addiction.  In this post I will use Suboxone and buprenorphine interchangeably.  The pharmacological properties of buprenorphine that were interesting in terms of potential use for addiction included the fact that it was a opioid mu receptor partial agonist and antagonist at the kappa receptor.  The partial agonist effects relevant for addiction such as euphoria and sedation occur at the lower doses and the antagonist effects occur at higher doses.  The antagonist effects like preventing respiratory depression were thought to put a ceiling effect on this side effects and make it safer than pure mu receptor agonists that would produce dose related toxicities.  In the Suboxone course the mixed agonist/antagonist effects were described as producing less toxicity and less risk of abuse.  The naloxone component of Suboxone is a pure mu receptor antagonist.  In the course I took, the explanation for the combination of buprenorphine and naloxone was that it reduced the risk of intravenous drug use and that this had occurred in Europe and it resulted in several deaths.  The company also sold Subutex which was buprenorphine only and indicated for use in pregnant women.

The pharmacodynamics and pharmacokinetics in real life can differ quite a bit from the idealized cases that the initial marketing and advertising was based upon.  Like many medications it can be a life changing drug.  People can recover and break the cycle of addiction, recovery and relapse and go on to productive lives.  It is the outliers that physicians need to be most concerned about.  In real life there are always going to be people who get significant side effects even at low doses and cannot tolerate the drug.  There are also people who tolerate the drug at high doses and do not experience the ceiling effect of mu receptor antagonism.  The people are probably very low in number but they are significant because they are not protected by the ceiling effect that is supposed to be there from the drug.  Drug addiction always attracts or produces a significant number of people who become amateur pharmacologists and use the drug to facilitate their addiction.  The word gets out and suddenly buprenorphine has street value (about $1,000 for a 1 month prescription) and opioid addicts can use it when they run out of heroin or oxycodone.  In a few people it is their preferred opioid because it has a longer half life.

The politics of Suboxone are as complicated as you will find in the pharmaceutical industry.  There are plenty of conflicts of interest in terms of how the drug was initially marketed and plenty of crossover between regulators and the company who developed, marketed and sold it - Reckitt-Benckiser.  According to a New York Times article last fall, the company was granted a period of exclusive sales that ended in 2009.  After that they went on the offensive to suggest that their new product - a Suboxone film was superior to the generic tablets especially in the area of child safety.  They stopped selling the Suboxone tablets at that point.  Insurance companies can work any controversy to their advantage and people on buprenorphine maintenance have been cut off based solely on the amount of time they have been taking the drug.  There are no scientific guidelines for how long a person should take buprenorphine and like most drugs used for maintenance therapy there will never be a study that looks at that question due to the expense.  Most experts would agree that if you have a severe addiction and have recovered based on buprenorphine there is no reason why you would be cut off.  In fact discontinuing buprenorphine seems to present a more significant problem as dose is tapered to 2 mg and  lower.   We also have a familiar political theme in the issue of opioids with the government seeming to create the problems in the first place and now saying: "Trust us we have the solution."  That may have explained the desperation in the descriptions of how public health officials were trying to increase Suboxone prescribers to address a public health opioid epidemic that was a likely result of government initiatives to improve the treatment of pain.

Suboxone has become a problem for the same reason that every other drug becomes a problem - unrealistic expectations, conflicts of interest, and a knowledge deficit on the part of the practitioners.  The title of the New York Times article illustrates how the press can look at the dual nature of drugs and imply that there is a larger problem.  I don't know of two many drugs that do not have a "Dark Side".  The negative trends in buprenorphine use can be reversed but it will take more than the suggested strategy in the NY Times article.  Here are a few ideas:

1.  The CDC needs to get involved and look at Suboxone/buprenorphine related deaths and study it in the same manner that they studied methadone.  It would be very instructive to see exactly where Suboxone/buprenorphine falls on the spectrum of deaths/100 kg MME (milligram morphine equivalents).  The expectation of some in the article is that it is much safer, I would prefer to see the numbers.  Only the CDC has access to the detailed data to look at this issue.  I would take it a step farther and suggest that the CDC recalculate this table on an annual basis as a key metric in reversing the significant public health problem of accidental opioid overdose deaths.

2.  The physicians prescribing the buprenorphine need to be highly motivated and well versed in prescribing medications to individuals with addictions.  The NY Times article suggests that there are many who take an entrepreneurial approach to the prescription of buprenorphine with cash only practices that vary from $100 - $250 a visit.  I have no problem with cash only practices if there is a quality approach.  By definition that involves a lot more than handing someone a prescription in 5 minutes.  The problem is the rest of what happens during that time is poorly defined.  The original prescribing information said that the physician needed to refer the patient to counseling services.  In many presentations of research that I have seen there is a clear movement to illustrate that - counseling adds little to nothing to outcomes when buprenorphine is prescribed.  There are problems drawing that conclusion about this research given the modest outcomes of the buprenorphine treatment.

3.  At least part of the interview of any patient recovering from the severe addiction that occurs with opioids is assessing their functional capacity.  What are they doing on a day to day basis and is that routine consistent with both recovery and a lack of cognitive side effects from the buprenorphine?  Being able to corroborate that improvement with a third party makes it even more reliable.

4.  A big part of the unconscious aspects of addiction is the behaviors that are present to continue the addiction despite the best conscious efforts of the person affected.  Good examples include craving, lying, and hiding use from others.  That requires prescribing physicians to engage their patients at this level and not develop a law enforcement transference.  A lot of physicians don't know how to respond to an accusation of: "You don't trust me!" when there is a question of the need for a toxicology screen or a discussion of a positive toxicology.  The interpersonal aspect of treatment is very important and it received no attention in the standard Suboxone prescribing course.

5.  Continued work on a model of treatment looking at all of the potential positive factors is needed.  There is nothing worse in medicine than to treat a scientific topic like a political one and not have a rational approach to the person with the problem.  Like the original course I took, there are  people out there who say that buprenorphine prescribed out of a physicians office is all that is needed.  Is that the case when you have a person who takes two to three times the prescribed amount to get high?  Or the person who is crushing it and snorting or injecting it?  Or the person who is selling it on the street to get purchase heroin?  Or the person who can't function due to cognitive problems at 2 mg a day?  Or the person who is hospitalized for recurrent bowel obstructions due to severe constipation?  As the prescribing physician - are  you confident that you can accurately screen for these problems?  What about competing approaches like the long acting mu antagonist naltrexone injections?  Where does 12-step recovery like Narcotics Anonymous fit in?  Where do sober housing and residential treatment fit in?  And finally - where can a person get detoxified and should anyone be forced to go through acute opioid withdrawal when they are incarcerated?

All of these questions are currently unanswered.  But like most treatments in medicine, the solution is typically a lot more than a pill.  Drugs with addictive potential always add the complication of significant financial gain from a captive audience.        

George Dawson, MD, DFAPA

Deborah Sontag.  Addiction Treatment With A Dark Side.  New York Times. November 16, 2013.

SAMHSA.  Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction.  A Treatment Improvement Protocol.  TIP 40.

NICE.  Naltrexone for the management of opioid dependence. 2010.

NICE.  Methadone and buprenorphine for the management of opioid dependence.  2010.

The FDA and Opiate Regulation

Does the FDA have a clue about the safe prescribing of opioids?  Based on their September 10 press release we are about to find out.  If you go to the FDA web page this appears to be the most relevant document.  It contains the following warnings:

BOXED WARNING

In the boxed warning in Highlights, include the following text:

• Tradename exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk before prescribing, and monitor regularly for development of these behaviors or conditions. (5.1)

• Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely, especially upon initiation or following a dose increase. Instruct patients to swallow Tradename (formulation) whole to avoid exposure to a potentially fatal dose of (active opioid). (5.2)

• Accidental consumption of Tradename, especially in children, can result in fatal overdose of (active opioid). (5.2)

• For patients who require opioid therapy while pregnant, be aware that infants may require treatment for neonatal opioid withdrawal syndrome. Prolonged use during pregnancy can result in life-threatening neonatal opioid withdrawal syndrome. (5.3)

For products with an interaction with alcohol, also include the following:

• Instruct patients not to consume alcohol or any products containing alcohol while taking Tradename because co-ingestion can result in fatal plasma (active opioid) levels.  (5.4)

As I read through these warnings I have several associations.  First off, physicians were told 12 years ago in JAMA that they were undertreating pain, misunderstood pain, and that pain treatment needed to change.  That was a naive document that depended on an assumption that pain could be "quantitated" on a 10 point scale.   Over a decade and 100,000 opioid overdose deaths later we are not told that providing this information on drug labels will make a difference.  That leads me to my second association, there is nothing in the above warning that I didn't learn in medical school 30 years ago, including the risk of neonatal withdrawal.  The third association is that this definition and intervention is almost completely naive about addiction.  A person with an addiction does not care about dire warnings.  They don't care about their pain ratings.  They care about acquiring and using addictive drugs.  It is the nature of addiction.  Their entire conscious state has changed. The tendency toward opiate addiction or not is probably biologically determined and a doctor cannot predict who is at risk.  If you take an initial dose of opiate and experience intense euphoria, high energy and productivity, and intense sense of well being or feel like you finally have become the person you always wanted to be - you may be a person at high risk for opiate addiction. It doesn't really matter if they have a chronic pain disorder.

What needs to be done?  What should the FDA being doing immediately.  The four most important misconceptions driving both the epidemic of opioid dependence and the accidental overdose trend are:

1.  Opioids are a silver bullet and will eliminate chronic pain if the dose is high enough.

2.  Once a maintenance dose is achieved the level of pain relief should be constant.

3.  Opioids are only taken for primary gain - the analgesic effect or the elimination of pain.

4.  Opiates - prescribed by a doctor will not lead to reactivation of a previous addiction.

What do people need to know now?  Probably not the new package insert for opioids.  Most physicians don't read it.  Every person taking an opioid need to know that it can affect their subjective state in such a way that it will place them at risk for addiction.  They need to know at that time that they need to contact their physician and discuss it and the possibility of alternate or more closely monitored treatment.  They need to know that there is no medicine that will treat chronic pain into remission.  Physicians need to know a number of things including the fact that there is no medication that will eliminate chronic pain.  They also need to know that it takes time and detailed evaluations (calls to pharmacy, tox screens, limited prescriptions, assessment of functional capacity) to optimize treatment and prevent addiction.

The warning on a package insert from the FDA containing seriously dated information will not do it.  Dire warnings about an epidemic won't do it.

George Dawson, MD, DFAPA