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.

The NY Times Opinion On Congress and the Opioid Epidemic

The NY Times came out with an opinion piece of the opioid epidemic on May 16 (1).  In their opinion it was a good thing that Congress had finally decided to "get involved."  They emphasize the need to fund treatment and prevention programs.  But wait a minute, didn't Congress already approve the The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA).  That act was supposed to provide equal treatment for mental disorders and addictive disorders.  Here it is a few years later and we are supposed to be still trying to fund treatment despite a specific piece of legislation was was already supposed to provide funding?  In fact, this same editorial board came out with a very rosy assessment of the MHPAEA three years ago and they were wrong back then as well.  In that link, I posted reasons why the parity act would fail and of course - it did.  That failure is the only reason the editorial board is now calling for funding for treatment and prevention programs,  I criticized their original post because they lacked anyone with medical expertise on their panel and they did not seem to know how health care works or why Congressional intervention does not work. It looks like the same mistake has been repeated.  At some point we need to recognize that the opinions and legislation about health care aren't worth the paper they are printed on.  At least from the perspective of the prospective patient or the physicians who are trying to treat them.

This piece does reflect a dim grasp of the health care system in this country that is set up by Congress in the first place.  Some of the suggestions made me want to laugh out loud.

"The federal government can make the biggest difference by expanding high-quality treatment programs. States, which have more sway over doctors and hospitals, need to do more on the prevention side by placing limits on opioid prescriptions. States can encourage doctors to order alternative pain treatments, like physical therapy, and require insurers to cover those services." (1)

This seems to assume that the federal government is somehow interested in quality while they are setting up managed care organizations that really have nothing to do with quality.  Everything is set up to be cost-effective (translation = cheap).  There is nothing cheaper in the way of mental health care and treatment for addictions than refusing to fund it and that is a routine occurrence in spite of the MHPAEA, the bill that was supposed to put the care of mental illnesses and addictions on par with other medical conditions.  The second error in this paragraph is the idea of a bureaucrat somewhere placing limits on opioid prescriptions.  That will immediately alienate the majority of the physician workforce that currently prescribes opioids appropriately and of course the patients of these physicians.  And finally the idea that alternate treatments will be covered misses the cultural contributions to the opioid epidemic and the fact that Congress doesn't seem to be able to mandate insurance companies to do much of anything.  If they can't mandate equal coverage for mental illness and addiction, why would physical therapy be any different?

On the question of how much legislation must be written and how much money appropriated, the money figures quoted range from $600 million to $1.1 billion to address the treatment needs of 435,000 regular heroin users, 1.9 million people who are regular prescription opioid users, and 4.3 million people engaged in non-medical use of prescription painkillers each month.  Considering only the prescription of buprenorphine for medication assisted treatment of opioid use disorder and the $1.1 billion dollar figure, at about $1,000/month for buprenorphine, that figure would result in the treatment of 92,000 individuals and that is not including the cost of medical evaluation and administration of the drug.  That is less than a quarter of the heroin users and less than 10% of the painkiller users.  It also does not fund any of the additional treatment services including addiction counseling and a continuum of sober support and housing.

In situations like this, seeming to address the problem by political one upmanship is always tempting.  A Governor is quoted in the article giving her opinion that the cause of the current epidemic is the prescribing practices of physicians.  I am sure that many legislators take the same concrete approach to problems but this is a much more nuanced problem.  Technically speaking - all physicians leave medical school knowing how to prescribe opioids.  Not all of them are good at managing the relationship with the patient or telling patients what they might not want to hear.  The commonest errors I see in prescribing addictive drugs to people has nothing to do with technical expertise of the physician.  It has to do with the idea that the patient is in distress and that it is the physician's job to do something about it.  Many of these physicians have a difficult time balancing the decision to prescribe an addictive drug versus the potential harm of addiction or the harm of not treating a pain syndrome that does not respond well to opioids.  Many of these same physicians lack an understanding of addiction and the fact that it is possible to continue to take an addictive medication even though it is providing no symptomatic relief from pain.   The third problem is the patient's lack of insight.  There a lot of biases when it comes to addiction and assigning responsibility.  There are numerous arguments about whether addiction is a disease or not and these are generally arguments about who is responsible for the addiction and its treatment.  I don't think that there is any doubt that a person who is addicted to opioids will behave in a predictable manner to keep the addiction going.  They will not tell their physicians that they have an addiction and in some cases try to get extensions on prescriptions, escalate the dose of a prescription, get more opioids from non-medical sources (dealers or acquaintances) or use the opioid for a reason that it was not intended - usually insomnia, anxiety, or depression.  How do legislators address this complex problem?  Basically by blaming physicians and passing legislation that doesn't make any sense.

It is important to remember that this epidemic did not start in a vacuum.  There was an activist movement among some professional societies and regulatory bodies to treat pain more aggressively.  Looking at past  New York Times editorials, some of this was recorded and in at least one case, the opinion came down on the side of aggressive pain treatment.   Congress and the media seems to have come full circle on the issue of opioids and is ready to head back in the other direction.  The news can be a powerful source of influence in encouraging people to use public health measures to stop this epidemic.  That can be as basic an idea as not hoarding leftover opioid painkillers and discarding them.

Hoping that Congress will solve the problem, when they were supposed to 7 and 22 years ago, does not seem like the best idea.  If they went back to sleep - nobody would notice the difference.


George Dawson, MD, DFAPA



1:  The Editorial Board.  Congress Wakes Up To The Opioid Epidemic.  New York Times May 16. 2016.

2:  The Editorial Board.  Making the Pain Go Away.  New York Times.  March 4, 1994:

"The new guidelines, issued in detail for physicians and in brief for patients, call for treating pain early and aggressively, starting with the simplest options, like aspirin and acetaminophen, and progressing through mild opiates to more potent drugs like morphine."

And....

"But there are scant data from scientific studies to document whether or not marijuana is as effective as or better than other anti-nausea drugs. The same outdated attitudes that inhibit the use of narcotics for pain relief should not be allowed to suppress clinical investigations into the therapeutic uses of pot."

Opiates And Moral Dilemmas For Physicians

I became aware of an article from Reason magazine written by a physician Jeffrey A. Singer titled Physicians Face A Moral Dilemma In Conscription on War on Drugs (1). In keeping with the main theme, the subtitle was “In the government’s new war on opiates, physicians and their patients find themselves caught in a crossfire.”  Physicians are generally in the crossfire of any number of government healthcare reforms. The opening lines of this essay should not surprise any physician.  We have been in the crosshairs for thirty years.  There is a tangible difference in the War on Drugs.  In the 1990s, I can recall a vague threat about incarceration for not doing my notes properly.  That wasn’t a threat to me specifically but an entire clinic of physicians than I belonged to at the time.  In retrospect it sounds absurd, but that the was pre-911 days when the FBI spent a lot of time reading physician notes and deciding whether or not they had committed health care fraud by not doing enough documentation.  These days physicians can be prosecuted and incarcerated for the way that they prescribe opiates. The threat is much more real.

Dr. Singer’s introductory paragraph points out that when any health crisis occurs politicians are eager to step up and offer their solutions and throw a lot of money at the problem.  In this case President Obama is building new drug addiction centers and “training” government physicians on opioids to the tune of $100 million.  Hillary Clinton is promising $10 billion as a criminal justice initiative as grant for drug treatment centers and training for first responders to administer opiate antidotes.  I have never seen a single politician or government bureaucrat acknowledge that the reason why the opiate epidemic exists has to do with policy initiatives that occurred right around the year 2000.  At that point, physicians were encouraged to treat pain more aggressively and with fewer checks and balances than they had in the past.  The cumulative effect of these policy changes was a lower threshold for prescribing opiates for chronic noncancer pain and a removal of some of the gatekeeper mechanisms – like getting second opinions from pain specialists on this practice.

The First War on Drugs was described as the initial prohibition of opiates and cocaine by the Harrison Act in 1914.  Singer describes a scenario where a physician who would prescribe an opiate to help a patient “cope with their addiction” as being in conflict with the law.  The Harrison Act prohibited physicians from prescribing opiates to maintain an addiction.  He cites this example as being the first moral dilemma.  It is more complicated than depicted.  There have always been a number of physicians who consciously or unconsciously maintained large numbers of patients in addiction and that was their medical practice.  That practice does not pass current conflict of interest considerations much less the ethical obligation of physicians to do no harm.  It is a given that legal interventions are generally blunt instruments for protecting people from their problematic decision-making and that a complete picture of all of the data (the number of people addicted by medical treatment versus non-medical sources) is never clear.  Is there a problem with suggesting that physician themselves should not be a primary source for creating and maintaining addiction?  The main problem is that even the most well-informed and well-intentioned physician can end up with a patient who is addicted to a medication.  There is currently no known way to prevent that.  Are those physicians criminals in any way?  I don’t think so.  At the same time, should there be a prohibition against physicians setting up a practice that maintains high number of patients in addiction, does nothing to facilitate their recovery from addiction, and has no other purpose – of course there should be such a prohibition. 

The next argument in the essay has to do with the safety of opiates versus alcohol.  This is a common argument by people who see nothing wrong with the legalization of drugs.  I am not suggesting that Singer is making this argument; he is trying to point out that opiates are relatively safer than alcohol and alcohol is a legal drug.  I think that he is wrong on several counts in this argument.  The first point has to do with the overall toxicity of alcohol.  He cites a number of diseases that have to do with the long-term toxicity of alcohol.  Alcoholic cirrhosis for example is typically the fifth or sixth leading cause of death in middle-aged men.  The estimated dose required in most cases is 15-pint years or drinking one pint of whiskey per day for 15 years (2).  Doing a quick calculation shows that this is about 143.26 grams of ethyl alcohol per day.  The progression to cirrhosis will vary based on sex, genetic factors, and rates of metabolism.  The overriding point is that alcohol consumption at this rate is limited to a small percentage of drinkers and the population exposure to alcohol is relatively stable based on current legal and cultural factors.  A related issue is that if you are alcohol dependent tolerance and withdrawal phenomena may lead to a marked increase in consumption – up to 750-1,500 ml/day in order to maintain blood levels high enough throughout the day to prevent withdrawal.  The exposure of multiple tissues over time causes the damage.

The primary mechanism of injury and death from opiates is respiratory ataxia and arrest by the direct action of the drug on small clusters of cells in the midbrain and medulla.  Opiates have a direct effect on the center that determines respiratory rhythm and the center that responds to chemical changes due to oxygen deficiency and carbon dioxide accumulation.  Benzodiazepines, alcohol and sleep medications are often involved in these situations and have a combined effect.  Alcohol in high enough doses can have a similar effect in depending on the individual and their state of tolerance.

Looking at the acute mortality related to alcohol and opiates, I don’t think that there should be any doubt that opiates are probably more lethal than alcohol.  The CDC states that about 2,200 people die every year from acute alcohol poisoning (3).  The population at risk appears top be 38 million binge drinkers.  Men ages 35-64 are at highest risk.  In 2014, there were 18,893 overdose deaths from prescription painkillers and 10,574 deaths from heroin overdose (4).  In this case the estimated populations at risk include 1.9 million people with a prescription painkiller problem and 586,000 heroin users.  Furthermore the death rate from prescription painkiller and heroin use parallels the availability.  I am puzzled by the author’s suggestion that opiates are “much safer” and that there is “honest disagreement among health care practitioners over just how harmful long term opiate use can be…”.

I guess that I am one of those disagreeable health care practitioners.  Anyone can fact check the above argument for acute toxicity and I would encourage a close look at the trendlines over the past 15 years.  If you look at this lines, you will find that the rate of deaths due to heroin overdose was relatively stable for at least a decade before a sizable number of prescription painkiller users decided to start using heroin.  The decision is a strictly economic one.  The most commonly abused prescription painkiller costs a dollar per milligram on the street.  Addicts are typically using 120-240 mg per day.  The equivalent amount of heroin can be purchased for about ¼ as much.  The end result is that stable rate of heroin overdose deaths has quadrupled in the last 5 years.  It is stark to contemplate that the total opiate death rate is based on a population at risk that is about 10% the size of the drinking population at risk.

Dr. Singer describes the movement that led to increased opiate prescribing at the beginning of the 21^st century as “enlightened” and “compassionate.”  He uses the term opiophobia as the irrational fear that doctors and patients have about these medications.  I think it is very clear that these advocacy groups and bureaucrats had no clue that increased access would lead to an epidemic of addiction and overdose deaths.  The moral dilemma for physicians is not colluding with law enforcement in the War on Drugs and “cutting patients off.”  The moral dilemma is practicing sound medicine in a system that blames them for not prescribing enough opioids and then ten years later blames them for prescribing too many.  All of this occurs against the backdrop of a culture that has an insatiable appetite for intoxicants in a country that has one of the highest per capita opiate consumption rates in the world.  The moral dilemma for physicians is recognizing that they can’t predict who will or not become addicted to an opiate and that many physicians do not have the skills necessary to not prescribe to patients who either really don’t need the drug or are probably addicted to it.

There is more than one moral dilemma in the opiate epidemic.  On the patient side should you let your doctor know if you have an addiction before the opiate prescription is written?  Should you let your doctor know that the first pill from the prescription left you feeling euphoric, energetic, confident and like you have never felt before in your life?  Should you let your doctor know that you are continuing to take prescription painkillers even though they don’t work for the pain or because the pain is gone?  Should you tell your doctor or pharmacist know that you suddenly have access to all of the opiates from a deceased family member who was in hospice care and ask how to keep them off the street?

There are many moral dilemmas associated with opiates for everyone and very little moral guidance.

      

George Dawson, MD, DLFAPA


Supplementary:

To calculate the mg alcohol in a pint of whiskey:

1 pint = 473.18 ml

473.18 ml x 0.4 (percent alcohol) x 0.757 g/ml (specific gravity of alcohol) = 143.26 g ethyl alcohol

References:

1:  Singer JA.  Physicians Face Moral Dilemma In Conscription on War on Drugs.  Reason.com  March 23, 2016.  Accessed on March 25, 2016.

2:  Lefton HB, Rosa A, Cohen M. Diagnosis and epidemiology of cirrhosis.  Med Clin  North Am. 2009 Jul;93(4):787-99, vii. doi: 10.1016/j.mcna.2009.03.002. Review. PubMed PMID: 19577114.

3:  Centers for Disease Control and Prevention.  Alcohol Poisoning Deaths.  CDC Vital Signs, January 2015.

4:  American Society of Addiction Medicine.  Opioid Addiction 2016 Facts and Figures.  ASAM web site accessed on March 26, 2016.   

       

The Beginnings Of True Pharmacosurveillance

From:  Morbidity and Mortality Weekly Report (MMWR)  October 16, 2015/ 64 (9): 1-14.

I am an advocate of real pharmacosurveillance of anyone prescribing medications in the United States.  To some that might seem like a controversial statement and it needs to be argued at a couple of levels.  There will be some privacy advocates who suggest that medication information is protected information.  Sensitive medical information can be extrapolated from prescriptions and all medical diagnoses are not seen as equal in the eyes of employers or average citizens.  In this era, the knowledge that a person has a significant amount of specific medication in their possession may also put them at risk for theft or exploitation.  There are very good reasons for making sure that this information is not leaked to the general public.  The overriding argument is public safety defined as making sure that a person seeking medical help is going to see competent physicians or in this era competent prescribers.  There are many reasons why a prescriber may not be competent and may put patients at risk, but one of the most significant reasons is that they have developed a practice or prescribing that makes them an outlier.  They are prescribing medications or combinations of medications in a manner that is not like the majority of practitioners. That prescribing pattern may be frivolous or unsafe.  In the case of unsafe patterns, the practitioner should receive immediate feedback and where necessary intervention.

Some reviews currently happen at some level in the US.  In hospitals and care systems where there is routine review of physicians, some cases are reviewed prescribing patterns are observed and they are given feedback.  That process is limited by a lack of standardization and objectivity.  Just a few cases may be reviewed when today's information technology (IT) capability allow for reviewing all of a physician's caseload all of the time.  The review is often part of a larger process like an annual review where there may be conflicting agendas like spinning the review to make the person look as good or as bad an an administrator wants them to look.  Physicians can also be contacted by managed care organization (MCOs) or pharmaceutical benefit managers (PBMs) with letters expressing various concerns.  Examples might be patients who have filled only one prescription for antidepressants, patients seeing multiple prescribers, and polypharmacy.  These letters are often poorly thought out, probably don't apply to the physician or patient at the time the letter is sent, and seem to be heavier on public relations than the technical details of prescribing medications.  In some cases these reviews can be totally inappropriate.  To cite an example, a reviewer notifies nursing staff that a patient on lithium needs follow up and immediate blood tests upon discharge because the inpatient physician has not ordered the appropriate tests when they do not have the most recent records, have not spoken to that physician, and don't know that all of the testing has been done.

Another very relevant question for pharmacosurveillance is: "Who owns the data?"  Any managed care company that I am aware of treats patient data as their own proprietary data whether they know what to do with it or not.  I gave the previous example on this blog of asking a managed care executive for permission to use deidentified brain images for teaching purposes and being told: "Why would we want you to use our data?" despite the defined teaching purpose of the institution and a long history in medicine of teaching all of the available abnormal findings for the purpose of developing better diagnosticians.  Prescription and pharmacy data has an even more clandestine history.  Most physicians were not aware until very recently that all of their prescription data was collected from pharmacies everywhere by a company called IMS America and that information was used primarily by pharmaceutical company sales forces to monitor the products being prescribed and whether their detailing people were having an impact on those prescriptions.  The individual physician was not able to see these records or look at the trends in their prescribing data over time.  The data collection was centralized only for the purpose of selling the collected data to pharmaceutical companies or (for the past 15 years or so) buried in clinic or hospital electronic health records.  The best a physician could do would be to request prescribing data on a particular patient from their pharmacy.  That might result in 20 or 30 faxed pages of lines and lines of prescriptions, usually encompassing only the most recent years.

The state may not only claim the data, but set in place mandatory rules about how practitioners collect the data and transmit it to them.  In the state of Minnesota, all practitioners treating depression are mandated to have their patient complete PHQ-9 rating scales for depression and have those results sent to the state.  The state also monitors prescribing data on stimulant prescriptions for children and mandates that any person taking an antipsychotic medication needs to sign a written consent form.   Currently 49 of 50 states participate in Prescription Drug Monitoring Programs (PDMPs) to track drugs classified on the Controlled Substances Act Schedules II - IV.  The PDMP programs were originally set up to help law enforcement identify illegal activities with controlled substances but developed into a resource for physicians who wanted to know if their patient was getting multiple prescriptions or prescriptions that increased the risk of medications that they might be prescribing.  These pre-existing systems led the CDC and the FDA to develop the Prescription Behavior Surveillance System (PBSS) to look at the trends in the prescriptions of controlled substances.   Typically all pharmacies within a state submit data on controlled substances within a week of the prescription being filled.  The PBSS categorizes all of the data into three categories: benzodiazepines, stimulants, and opioid analgesics.  Buprenorphine is classified in the opioid analgesic category even though the primary use is for treating opioid dependent patients.  Tramadol was not included in the database until it was reclassified in 2014.  There is also a miscellaneous category that includes zolpidem and carisoprodol.  I think it probably makes sense to include GABA enhancing sedative hypnotics like zolpidem, zaleplon, and eszopiclone in the benzodiazepine category.

The preliminary data from the PBSS system that was just released in October is very interesting.  In terms of a representative sample, the eight states reported cover 1/4 of the US population and represent all 4 US Census Bureau Regions.  Prescription rates were calculated as the prescription rate per 1,000 residents as given by the most recent Census data.  Perhaps most surprising is that the rate of opioid prescribing approaches nearly one prescription for every state resident in some states in some states and the rate of opioid prescribing is twice as high as the rate of benzodiazepine or stimulant prescribing.  There are two to four fold differences in state-to-state prescribing of controlled substances across the board.   The top 1% of opioid prescribers in Delaware wrote for one out of four opioid prescriptions in the state.   The top decile of prescribers account for 50-60% of opioid prescribing but that decile does not solely account for state-to-state differences.  Specialists in pain clinics (pain medicine, surgery, physical medicine) were more likely to write more prescriptions per day but are thought to account for < 20% of all opioid prescriptions per day.   The authors suggest that most of the prescriptions in that category are written by general practitioners, family medicine, internal medicine, and midlevel practitioners.

Overlapping prescriptions ( benzodiazepines and opioids and long-acting and short acting opioids) were common.  Multiple provider episodes or MPEs defined as a resident filling a controlled substance prescription from 5 or more prescribers at 5  or more pharmacies in any 6 month period varied significantly by state, age, and the number of controlled substance schedules added.  The totals ranged from a low of 4.4/100,000 residents in Louisiana to 66.8/100,000 in Ohio.  An overall first impression of this system is that there are limitation but it clearly provides valuable information on prescribing behavior relevant to controlled substances.

The current epidemic of accidental overdose deaths was the driving force for the PBSS system.  It shows that a pharmacosurveillance system is possible, but that there are some limitations.  Data quality as inputted from the pharmacies needs to have quality control measures to assure consistency.  An ideal system would also include a diagnosis or indication.  Physician speciality would also be a useful marker.  I think that the best use of a system like this would be to allow physicians to mine their own prescription data and see how they compare with other physicians in general and within their own speciality.  Specific strategies could be developed for self correction at the earliest possible stages.  I wrote about a pharmacosurveillance system used in Wales in a previous post.  The top 5 drugs causing complications in that system were opioids, antibiotics, warfarin, heparin, and insulin - in that order.  With a sophisticated system it would be possible to pick up significant adverse drug events and monitor those events as well.    

All of the talk about patient safety these days is really about patient safety being practiced in the silos: health care businesses, hospitals, and clinics.  Places where individual health care data is considered proprietary - at least until there is a complication big enough that the state authorities mandate that it be reported for investigation.  These businesses have an inherent conflict of interest in reporting adverse drugs events and severe complications.  Pharmacosurveillance should be out there across the entire health care landscape.  It should not depend on reports about complications made by businesses that are in effect protected by patient privacy.  Complications can be actively sought out and investigated any time a prescription suddenly stops or changes.  This data also needs to be freely available to physicians so that they can look at their prescribing data relative to their peers and make changes where necessary.

It is time to view the process as as a way to learn about how to provide the safest possible environment for patient care,  rather than a way to "catch" somebody when something goes wrong.        


George Dawson, MD, DFAPA


References:

1:  Paulozzi LJ, Mack, KA, Hockenberry JM.  Vital Signs: Variation Among States in Prescribing of Opioid Pain Relievers and Benzodiazepines — United States.   Morbidity and Mortality Weekly Report (MMWR) July 4, 2014 / 63(26): 563-568.

2: Paulozzi LJ, Strickler GK, Kreiner PW, Koris CM.  Controlled Substance Prescribing Patterns — Prescription Behavior Surveillance System, Eight States, 2013. Morbidity and Mortality Weekly Report (MMWR)  October 16, 2015/ 64 (9): 1-14.

From Morbidity and Mortality Weekly Report (MMWR) October 16, 2015/ 64 (9): 1-14.

APA Misses On The Opioid Crisis - Several Times

The above infographic is courtesy of the CDC (see attribution for the direct link).  To those of us involved in treating addictions talking with many people who are addicted to opioids, getting them to see the problem, and helping them prevent accidental overdoses and death is an everyday occurrence.  The prescription opioid problem is widespread and has been a reality for the last 15 years even though it seems to have hit the news in about the last 5.  That probably coincides with heroin use starting to escalate.  The driving force for that has been economics.  Heroin is generally available in most areas for about a quarter the cost of diverted prescription painkillers.  In the past 5 years I have probably given about 50 lectures on the topic to physicians and graduate students and been actively involved in the clinical care of individuals with heroin addiction only or heroin addiction in addition to a number of other addictions.

When I got a post from the American Psychiatric Association (APA) on my Facebook feed last week it piqued my interest.  Part of what I teach is how failed policy is the root cause of the opioid epidemic and what physicians can do on an individual basis to correct the problem.  I was very interested to see what the APA had to say at a policy level.  Reading through the document that is really a blog post from the Medical Director the answer is "not much".  It appears that the APA has joined a Task Force of other professional organizations that includes that other great laggard the AMA.  They will be working to identify "best practices" and implementing them as soon as possible. Using Prescription Drug Monitoring Programs (PDMPs) is encouraged.  There will also be the focus on stigma.  Dr Levin states: "The APA maintains that substance use disorder is a medical condition that can be successfully treated, and we are actively advocating on behalf of the patients who are too often stigmatized by their community and disenfranchised by insurance carriers who fail to comply with mental health parity laws."

While there is no doubt that most people are biased against people with mental illness and addictions as well as their psychiatrists - I don't think that stigma has any traction in terms of increasing access to care or more importantly access to quality care.  I could argue that the APA support for the collaborative care initiative colludes with stigma-like biases.  That takes the form of "you don't have to see a psychiatrist - take this checklist instead."  I won't get into that today, only to say that I wonder how many people with heroin or opioid addiction are being seen in primary care clinics and being treated for anxiety, insomnia, or depression?  From what I see the numbers are significant.  But it is hard to fault primary care doctors because unless they are the prescribers of opioids, they may not realize that their patient has a problem with them.  There is also the issue of institutional stigma versus public stigma.  Public stigma or the type of stigma that everyday people have is more elastic and it usually depends on their experience with the problem.  If you live in a family where a member has a severe mental illness or addiction - you know that these problems are real, life-threatening, and you are ready to let people know that.  Institutional stigma is the type of stigma that governments and businesses can have, especially health care businesses.  They might grudgingly admit that there is some kind of problem largely because there is such a large secondary impact on medical and surgical services.  In some trauma centers over half of all admissions are primarily due to drug and alcohol problems.  At the same time,  institutional stigma is impervious to change.  It is codified in some texts on healthcare management and as noted in the APA blog post - not even amenable to change when new federal parity laws are implemented.  In terms of managing health care systems there is nothing like having a certain groups of disorders to shift resources away from in a pinch.  Mental illnesses and substance use disorders are that group.  The other considerations would include:

1.  Irrational policy initiatives:  There is no doubt that several policy initiatives to liberalize opioid prescribing were responsible for the start of this epidemic in or around the year 2000.  Making pain the "fifth vital sign", encouraging the use of opioids for chronic non-cancer pain, treating minor conditions with opioids, and a widespread policy initiative that encourage more aggressive treatment of pain even though specific measures were not know are among these initiatives.  I use the word irrational here to mean speculative initiatives that were not based on science.

2.  A serious misunderstanding of the current problem:  When all else fails blame physicians.  That is a highly effective political strategy that worked to consolidate control of the health care system under business and government.  To many of the politicians involved it flowed directly from their negative campaigning experiences.  In this case, the opioid problem is being framed at some level as a problem of inappropriate prescribing by physicians.  Some physicians are being subjected to criminal prosecution for deaths and complications that have resulted from opioid prescribing.  There are no references to the policy changes that occurred in the late 1990's that led to this change in physician prescribing behavior - the loss of gate keep functions in particular.

3.  A misunderstanding of the epidemiology of the problem: The upper decile of opioid prescribers (total number of prescriptions) account for 50-60% of all opioid prescriptions.  These prescribers are almost all family physicians, internal medicine specialists, and mid-level prescribers.  Available databases allow for rapid identification and intervention with these prescribers and that is where resources should be focused and not on all physicians across the board.  A mechanism for feedback on an individual physician's or physician extender's ranking in terms of their prescription of controlled substances is needed as well as individual access to that information.

4.  A serious misunderstanding for the overprescribing problem in general exists: As I have previously pointed out, opioids are one small group of medications that are overprescribed in the US.  Practically everyone who wants this problem to go away sees it as a cognitive problem or knowledge deficit.  If the physician involved just knew more they would not prescribe pain medications this way.  In fact, it is a much more complicated interpersonal, social and intrapsychic problem for physicians.  Until there is a widespread acknowledgement of this - all of the CME courses in the world on appropriate opioid prescribing will not change a thing.

5.  There is a widespread cultural problem:  Opioid hoarding in medicine cabinets across the country, neighbors sharing opioids and neighbors and family members discussing what is the best (translation best = most euphorigenic) is a major problem in the US.  Many politicians have agreed that America's "insatiable appetite for illegal drugs" fuels the international drug trafficking problem.  It also fuels the opioid epidemic.  There are very few initiatives focusing on cultural change.

6.  Misunderstanding the problems inherent in prescribing addictive drugs:  Most physicians are not aware of the unconscious and conscious elements that are activated in susceptible individuals when they take addictive drugs.  There are widespread misconceptions in this area that lead to the prescription of addictive drugs during active addiction,  not assessing the risk of prescribing addictive drugs to a person in recovery, and failing to assess some of the indirect signs of addiction in patients who deny that they have a problem with addiction.  There is also a belief among many physicians that if their goal is to help people that well intended prescribing will not lead to problems in the future.  

These are 6 areas that the APA could be focused on.  I don't think that you will see that analysis anywhere else.  I expect that "best practices" will fall disproportionately on the average physician and be a waste of time on their time and energy.  But it does fall back on the time honored political strategy of taking the heat off of the people who really failed and pretending it is a physician based problem.


George Dawson, MD, DFAPA


Attribution:

The infographic is from the CDC at this URL:  http://www.cdc.gov/vitalsigns/heroin/infographic.html#use

The CDC has done great work in this area and their site should be closely monitored for new data relevant to the problem.

The Myth of "Rescue" Medications

First off a clarification.  I am talking about the specific case where a short acting medication is added to a long acting form of the same medication and not "as needed" medication in order to determine the correct daily dosage.   In my line of work it occurs in two situations, long acting stimulants and their immediate release versions and long acting opioids and their immediate release versions.  I will illustrate that these practices are driven by myths about the medication rather than pharmacokinetics.  There is always the additional consideration about addiction lurking in the background, but the conscious and unconscious determinants of addiction frequently depend on the myths that I will be discussing about medication effects.

The example that I will use here is Concerta (long acting methylphenidate) compared with immediate release methylphenidate.  The graph from the package insert above shows the plasma concentration from a single 18 mg dose of Concerta and three successive 5 mg doses of immediate release methylphenidate.  As noted in the comparison of the curves and additional pharmacokinetic parameters the curve associated with three successive doses of immediate release methylphenidate is nearly identically replicated by a single dose of Concerta.

What is happening when additional doses of a immediate release methylphenidate are prescribed to a person who is already taking Concerta?  I  have seen this happen with sustained release stimulants and sustained release opioids.  I have seen it happen as a single dose of the immediate release preparation or multiple doses over the course of the day.  The patient is usually advised that this is a "rescue" medication that they should take if needed.  The first possibility is that the dose of sustained release medication has not been optimized and a higher dose of the sustained release medication needs to be given.  That is usually not the case.  The most frequent reason for taking the rescue medication is that the patient believes they are experiencing breakthrough symptoms and for a moment they need a higher dose of a medication.  There are serious problems with that concept.  As can be seen from the curves comparing Concerta and methylphenidate it does not make pharmacokinetic sense.  Any additional dose of immediate release methylphenidate on top of Concerta would greatly increase the expected plasma concentration at that point.

The main problem is that both ADHD and non-cancer pain are chronic conditions.  By definition they do not respond well to medications and they will not resolve typically with any amount of the medication.  Many people who take stimulants for ADHD assume that the human brain can be fine tuned with a medication.  There is also a widespread myth that they are cognitive performance enhancing drugs.  The real effects of stimulants are modest at best and there is no good research evidence to support a cognitive enhancing effect.  A similar bias exists for the use of opioids for chronic non-cancer pain.  The person believes that "If I take enough of this medication - my pain will be gone."  Study after study of opioids for chronic non-cancer pain shows that pain relief with opioids is modest at best, with results very similar to what would be expected with non-opioid medications like gabapentin and antidepressants.

There are secondary problems with believing a medication will produce perfect cognition or perfect pain relief.  The first is a tendency to see any medication with such powerful abilities as being able to solve a number of problems that are not the primary indication for the medication.  As an example, with a stimulant - if this medication has such a profound effect on my cognition maybe it can help with with other difficult problems like excessive appetite and weight problems or feeling like I don't have enough energy at certain times during the day.  With the opioid the  thought typically is that it can be used for mental pain as well as physical pain and it is used to treat anxiety, depression, and insomnia.  Whenever a medication is not used strictly for the prescribed indication there is a risk that it will be used for "what ails you."  The danger is dose escalation and addiction.  There is also the risk of attributing too much of an effect to the medication when it does not appear to be doing much.  A person may start to believe that they can't function without the medication but a detailed review of their target symptoms and ability to function shows that there has been a negligible effect.  And finally there is the danger of taking a medication that may produce euphoria, increased energy, and create a sense of well being and not realizing that at some point that is the only reason the medication is being taken.  I have had many people tell me that the medicine did nothing for their pain or cognition but that they kept getting refills because they "liked taking it."

There is what I call the Talisman effect, but probably to a lesser extent than with benzodiazepines.  Many people develop the idea that they are taking a medication that is much more effective than it really is and therefore they have to take it with them wherever they go.  They are conferring what are essentially magical properties to the medication and at some level thinking that they are unable to function in life without it.  They get anxious if they think about not having it or running out.  This not only causes a lot of unnecessary anxiety, but it also prevents the person from using other psychological or conditioning techniques that may work as well or much better than the medication.

These are some of the problems with the idea of taking a rescue medication if you are already on a long-acting form of the medicine.  Physicians in general do not do a good job of explaining these potential problems or even the basic problem of taking a medication that causes euphoria or reinforces its own use.  A more widespread recognition of these problems would go a long way toward curbing overprescription, overuse, and addiction to these medications.    

        

George Dawson, MD, DFAPA

References:

1.  Graph of plasma concentrations of Concerta and methylphenidate is from the package insert on FDA web site at:  http://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021121s014lbl.pdf

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.