Another PSA On Pain, Opioids, and Addiction

It turns out that Twitter is an inadequate forum for discussing the issue.  Twitter is an ideal format for discovering if a poster knows anything at all about the problem.  A lot of people don't and they seem to just be there to argue.  I don't have a lot of time to waste on political approaches to medicine.  Political approaches to medicine typified by managed care companies, pharmaceutical benefit managers, and government guidelines that are supposed to improve care but don't are the reasons we have an expensive, fragmented and inefficient health care system.

The apparent political factions on Twitter consist of pain specialists who take the position that pain care and access to opioids is now being rationed and their pain patients are being unjustly treated.  They claim there is a faction of addiction specialists making various claims that they take offense to.  But my experience there is the past few days is that these are all basically red herring arguments.  A few of those claims include the idea that addiction specialists would consider pain patients "drug seekers", would recommend treating pain with only acetaminophen, are calling pain specialists "quacks", and of course that addiction specialists have some interest in distorting and overplaying the dangers of opioids.  In some cases the arguments have gotten to the absurd claim that the pain advocates (or more appropriately anti-addiction contingent) claims that most heroin users start using heroin directly rather than using legitimately prescribed or diverted pain medications first.

Where is the reality in all of this distortion?  The reality centers like most things in medicine in primary care settings.  The hundreds of thousands of internists and family physicians who provide the bulk of care for almost all problems in the US.  As I have posted on this blog many times, the evidence from both the CDC and CMS is that the majority of these physicians do a good job with opioids.  Only a fraction of their number prescribes a disproportionate amount of opioids.  Many of these physicians have a bias to underprescribing if anything.  That means the bulk of physician punitive legislation about mandatory course for opioid prescribing for these physicians will be just that - punitive toward most physicians who already know about prescribing these medications.  That legislation is also untested in terms of whether it will have any impact on the physicians who are overprescribers.

The other facet of the problem is overprescribing in general.  Part of the quality problem in medicine today is that the business and governmental management systems are focused on a brief physician-patient encounter where some medication gets prescribed.  That is the focus of the encounter. Patients expect that and come in the door with a medication request.  That results in predictable overprescriptions of medications from many classes.  The classes that reinforce their own use - opioids, stimulants, and benzodiazepines are more problematic than the rest.

At the extremes of this landscape are the pain specialists on one end and addiction specialists on the other.  Both have a broad spectrum of quality settings from state of the art to nonexistent.  These specialists know this and they know there is very little that can be done about it except to mind your own business and do the best job possible.  There are pain clinics that are "pill mills" where there is an understanding that a cash exchange with a prescriber will get you a script that can be filled on site for opioids.  That prescription is then sold in the parking lot for diversion.  There are other pain clinics where no attention is paid to addiction, psychiatric comorbidity, polypharmacy or the functional capacity of the patient being treated.  There are similarly low quality addiction treatment facilities where people are warehoused with no active treatment.  Where there is no therapeutic environment because nobody in the program is willing to consider that they may have an addiction.  There are programs where there is no medical supervised detoxification.  There are programs where there is no medication assisted treatment for opioids or alcohol use.  There are programs that do not address psychiatric comorbidity.  There are programs based on some sketchy ideas that have no proven relevance in treating addictions.  The houses of both pain and addiction specialists are not perfect because of these serious flaws.  And let's face it - the regulators of every state in the union are to blame for having so many low quality pain and addiction treatment facilities open for business and accepting reimbursement for shoddy services.   

For a moment - let's return to the idealistic world of the Twitter protagonist where the position seems to be "I am all knowing and do a perfect job."  The realities will  differ based on whether you are on the addiction or pain specialist end of the spectrum.  To illustrate, I am on the addiction end and 100% of the people are see have addictions or substance use problems.  On any given day the problematic substances average out to about 30% alcohol, 30% opioids, 20% mixed, 15% stimulants, and 5% cannabis.  Of the opioid users 30-50% have chronic pain problems.  In every case, I have a detailed discussion with the patient about how their substance use problem evolved and what keeps it going.  Over the years I see thousands of people with these problems and in that process come to know a lot about the associated issues.  My opinion is not based on my personal experience or politics.  My opinion is based on understanding the problems of thousands of people that I am supposed to help.  For example, when somebody tells me that the "average" heroin user in this country starts using heroin rather than prescription painkillers - I can say that is unequivocally wrong.  I have heard all of the details about how heroin use begins and it is almost always with a prescribed or diverted pain medication.  When somebody tells me that taking a person who is addicted to opioids and who has chronic pain off of opioids is cruel - I can also say that they are wrong.  I have had those same people tell me that they have never felt better and in less pain in years.   I can also say the following based  both on research, theory and clinical experience:

 1.  A significant portion of the population is predisposed to addiction - 

My estimate would be about 40%.  When a genetically predisposed person uses an intoxicant their reaction to it is markedly different from a person who lacks that predisposition. Opioid users report an energetic hypomanic felling where they have mental clarity like they have never experience before.  In some cases they will say that they felt like they had become the person they always thought that they could be.  This is a highly reinforcing state that leads to more opioid use.

2.  If the population predisposed to addiction is significant - the only limiting factor is access or availability -

This is the basic reality of the current opioid epidemic and of course very drug epidemic (methamphetamine, cocaine) that the US has seen over the past 200 years.  It is quite easy to look down from the high perch of a low availability area with low addiction rates to a high availability area with high addiction rates and conclude that "there is something wrong with those people".  The usual conclusion has been that they are morally defective.  This is how addiction services have been rationed, poorly researched, and fragmented over the years.  Even if you subscribe to a top health plan in the country - it is likely that you will have poor access to quality addiction care because of these attitudes.

3.  The burden of prescribing medications that reinforce their own use falls squarely on the prescriber - 

It is above all else an informed consent issue.  The patient needs to know that the medication they are taking is not a panacea and that there are significant risks up to and including addiction and death.  They also need to know that these medications can have cognitive side effects and affect their day-to-day functioning.  They should not be prescribed solely out of the notion that the physician feels like they need to do something for the patient.  There needs to be a pain diagnosis and treatment plan.  In the case of chronic pain the patient needs to know that there is no known medication that completely alleviates chronic pain and therefore continued dose escalation of opioids is not a solution.  The treatment plan needs to contain more elements than taking the opioid prescription.

An associated prescriber issue is polypharmacy.  Chronic pain is frequently associated with anxiety, depression, and insomnia.  That can lead to a contraindicated polypharmacy environment that includes a benzodiazepine, a z-drug, or a sedating antidepressant used with the opioid.  It can also lead to the patient taking alcohol or diverted sedatives on their own initiative with the opioid.

4.  Chronic pain patients taking opioids need thorough evaluations if possible -  

Some people in the Twitter debate seemed shocked by the idea that opioids are taken for reasons other than pain relief.  I suppose they would be even more shocked if they heard that there are people that take them who get no pain relief at all from them.  They taken them strictly because of the positive euphorigenic effects.  There are also people who take them despite the side effects for the same reason.  The first thing a physician needs to do is step back from the indication - prescription mode that most American physicians have been trained in to take a look at the entire prescribing landscape.

That means that is a person has come to idealize a medication or abusable substance they will start to use it for anything - insomnia, anxiety, depression, or "just to feel right to get through the day."  As many people tell me: "Look doc - if you can't get rid of this depression I know what I can take to feel OK for a couple of hours."  On Twitter and some other blogs readers are incensed that these behaviors exist and yet they are documented in the literature (see paragraph 6).

When I say if possible I am more aware of the fact that patients lie to physicians than non-addiction specialists.  I have had an endless number of patients tell me that they can get whatever addictive medication they want out of one physician or another.  The Mayo clinic had an addiction medicine conference three years ago and one of the presenters was a patient in recovery who basically talked about how he systematically lied to physicians to get opioids for years.  He talked about how he could identify a physician who would give him the script that he wanted and who would not.  In the case of the latter he would just move on to another clinic.

Many non-addiction specialists consider it to be poor form to suggest that patients lie.  That denies the basic reality that everybody lies.  It also denies the reality of addiction, that you are transformed into a person who is dishonest and a person that you never thought that you would become.  In the addiction field it is critical to acknowledge this to help people deal with guilt and shame so that they can recover.  The worst thing that can happen is to collude with dishonesty when the final result is the prescription of an addictive drug.  I do not consider it to be an issue that I can get this history when the physicians being approached for the medication cannot. It is all part of the illness of addiction.  On the other hand, if you are the opioid prescribing physician - the amount of information that you can get asking the direct questions about problematic use is not known until you try it.   

All things considered it is possible to treat people with chronic non-cancer pain with opioids.  I have been involved in that treatment before I switched to seeing only patients with addictions.  I consulted with some of the top pain experts in the state.  All the limits in this post need to be acknowledged and cautiously addressed.  The treatment of chronic pain is not perfect, I know that because I see a lot of the failures.  Addiction treatment is not perfect either.  The treatment needs to be highly individualized.

I wish that I could provide more clear guidance to the patients involved.  As an individual I cannot just start pointing fingers at the places (pain clinics and addiction treatment) that I think should be shut down.  I think that you need to depend a lot on your primary care physician referring you to places that he or she knows will do good work.  On either the addiction or pain end of the spectrum - there has to be more going on than the prescription of medications.

Even the most basic psychological models suggest that other cognitive, emotional, affiliative, spiritual and reconditioning changes need to occur.


George Dawson, MD, DFAPA 

  








   

Why Most People Don't Have A Mind For Medicine

The inspiration for this post was a story I just read about the "victims" of the crackdown on opioids.  A number of chronic pain patients were described who were only able to get pain relief from opioids.  They discussed being limited to arbitrary reductions in medications or monthly limits imposed by politicians.  In some cases the people taking pain medications were being treated like criminals.  They don't like being treated on the basis of people who are addicted to opioids.  I did a more extensive search and there are several articles out there like this.  The general tone of the article is that there are tens or millions of people out there with chronic pain and that since many of them need opioids for chronic pain aren't we overdoing it a little with the restriction on opioids?  Why should good people suffer just because some addicts misbehave and die?

Some of these articles attempt a semblance of balance.  They discuss the timeline of the opioid crisis based on policy changes and pharmaceutical marketing.  They may get the opinion of some experts than generally falls along polarizing lines.  In the end the reader is generally left with a definite viewpoint on what might be the right or wrong approach to chronic pain and the opioid crisis.  There is never an explicit statement about right or wrong approaches being the way we got into the opioid crisis in the first place.  Medicine is not a a field that you can generally approach with a pre-existing right or wrong bias - at least not for the majority of patients.

Most medical care is directed at a collection heterogeneous disorders spread across the entire population.  Each of these conditions has numerous etiologies and no clear cure.  That means from a medical standpoint it typically takes a number of trials to see if something works.  Since only a fraction of the target population responds to the intervention and a significant fraction of the target population does not tolerate it - the interventions are generally seen as being weak across the entire population.  That supports odd arguments like: "Antidepressants don't work" or "Beta blockers don't work for hypertension" or "Thiazide diuretics should always be the first line medications for hypertension".

It is also very tempting to look at the entire heterogeneous population and think: "Now we have a medication that can treat everybody.  This is the magic bullet for this disorder".  There are really very few medications that work that way.  The reason for the less than robust response blockbuster drugs is quite simple - a significant number of people typically do not respond or get side effects to the point that they want to discontinue the medication.   That negative response to medication is typically the main limitation when it comes to the overall effect of a medication on any population.  In my experience about 1/7 people cannot tolerate an SSRI type antidepressant medication due to side effects.  An addition 2/7 will not get an adequate therapeutic response.  On the other hand the 4/7 of the people that respond may feel much better and notice a complete remission of depression or anxiety symptoms.  Looking at the entire population the overall effect of the medication is not robust, but that does not mean that it might not be a life changing medication for some.

Opioids present a much different landscape because in many people they reinforce their own use irrespective of whether the medication works or gives that person significant side effects.  You read that correctly.  I have had people tell me directly that they got absolutely no pain relief from an opioid but they liked taking it so much they continued to get the prescription filled.  I have had people tell me that they got significant side effects from opioid medication but they kept taking it because they liked how it made them feel.  Keep in mind that there is always a range of these effects but I have never heard people describe these experiences with SSRI antidepressants.  The mere taking of an SSRI antidepressant does not reinforce continued use.      

This is the special dilemma with opioids and all medications that reinforce their own use (benzodiazepines, stimulants).  When a person says that they need to keep taking that medication - what does it really mean?  I will be the first to admit that they may need to take the medication and have treated chronic pain patients for years who were taking opioids.  They were still in pain to some degree but they also believed the opioid was providing them with some degree of relief.  The only visible sign that they could take opioids on a chronic basis was that they did not escalate the dose and did not get additional opioids or addictive drugs from other medical or non-medical sources.  The obvious question in this case is "Why don't you just increase the dose of opioid to get rid of the pain?"  The answer is that there is no medication - not even opioids that completely alleviate chronic pain.  I have had many acute pain sufferers tell me that they did not get much relief from acute pain with opiates until the non-specific effects like sleep took over.

Another factor to consider is that most chronic pain patients who come to addiction treatment centers feel markedly better and in less pain when they are tapered off opioids and placed on non-opioid medication for pain.  People are often surprised to hear that, but based on what I just said it should not be that surprising.  If you are taking a medication that will not completely eliminate chronic pain, has a lot of side effects, and biases  you into taking it and ignoring those side effects - how can you not feel better without it?

The final piece of the equation is addiction or severe opioid use disorder.  At this stage - the problem is compounded by the fact that a person needs to take the medication in order to function on a day by day basis.  If you happen to be a person with chronic pain - not being able to function in addition to the chronic pain puts you in an impossible situation.  That is especially true if you are escalating the dose of medication in order to try to recapture the original high, cope with an emotional state,  or  get some sleep.  In many of these situations the person will find themselves "cut off" from the clinic they attend because they have exceeded their prescribed amount of medications.  Because that precipitates acute withdrawal they may seek prescription medications from a non-medical source or start using heroin.

I hope that I have been able to convey the complexity of the situation with opioids for a chronic wide scale problem as opposed to other medications for similar problems.  The stimulus for this post is the usual swing in journalistic opinion with complex problems.  I was going to title the post: "Why journalists and politicians can't practice medicine".  Complex chronic problems in medicine cannot be oversimplified into binary solutions at this point in time.  Researchers are currently developing the tools that will allow us to identify subgroups in these populations and subject people to less trial and error.  At some time in the next 10 years, I expect that we will be able to rapidly identify who might be able to take opioids in a non-addictive manner and who will not be able to.  We might even have better medications for chronic pain that are safe and non-addictive by then.

In the meantime, a rhetorical approach casting some people as victims and  others as villains is unproductive and stigmatizing.  As I tell my students it is the difference between drawing inferences about people in a large city based on the amount of addiction there.  Twenty years ago in that large city children going to school would have to walk past three or four drug dealers.  As a result urban addiction rates were much higher than rural addiction rates.  Now that the rural kids have to walk past as many drug dealers, people in rural settings are addicted to heroin and dying of overdoses.  Exposure to drugs rather then moral superiority is the limiting factor.

To do well in medicine a physician needs to have good probabilistic thinking.  A lot of that process is acquired rather than learned on a rote basis.  Errors in this decision making process are almost guaranteed, but the only real problem are the physicians who seem to error all of the time.  That turns out to be a minority of physicians.  I expect that this group has difficulty managing both the treatment probabilities and interpersonal dynamics required to treat chronic pain, recognize addiction and implement the appropriate interventions.

One thing is for sure journalists, politicians, law enforcement, and insurance companies do not do a better job than the majority of physicians.  It is a major mistake to think otherwise.        



George Dawson, MD, DFAPA    





Supplementary:

Graphic is supposed to indicate that only a physicians with direct responsibility to the patient can appreciate the complexity of the situation especially when it comes to the nuances of addiction and chronic pain treatment.  It should be apparent that complexity can not be captured by rating scales.


Attribution:

Eyeball graphic is from Shutterstock "Untitled" per their standard agreement.
  

The Conscious Experience of Pain

Drawing of Pain Matrix from reference 2 with permission.

One of the main problems with the assessment and treatment of chronic pain is that there are no quantitative or even good qualitative measures of whether pain exists and how much pain is really there.  The current crisis of opioid overprescription began as an initiative to treat pain more aggressively and that started based on the use of a 10 point scale to estimate pain.  There are many problems associated with that approach but the main one is that it is completely based on the patients self report.  Self report is probably not the best measure when prescribing medications with a significant secondary gain component.  Since that scale is used as a basis for potentially high risk therapies - better metrics would be very useful.

That brings me to two papers that I caught a little earlier this year in JAMA Neurology on the Pain Matrix.   The first is a research letter on the pain matrix.  The authors define the pain matrix as the set of brain structure that are activated by nociception or pain perception.  As a general example they describe the general brain structures like the anterior cingulate cortex, thalamus, and insula.  They cite evidence that these activated structures are considered a possible biomarker for drug discovery and legal proceedings.  The paper is designed to test the veracity of this potential biomarker for pain.  Their model was the administer mechanical noxious stimuli to subjects with congenital insensitivity to pain.  These subjects had SCN9A mutations in the sodium channel of sensory neurons that results in loss of pain sensation but preservation of tactile sensation.  For a discussion of the polymorphisms of this gene see reference 3 and the link on Congenital Insensitivity to Pain (CIP) (4). There were two pain free subjects and 4 controls.  All subjects were scanned with a 3-T fMRI.  They were also asked to rate the stimuli on two dimensions - sensation and pain using a 0 (no pain or sensation) to 10 (most intense pain or sensation).

The test subjects and control reported the same responses to sensation in terms of the subjective ratings with mean ratings(standard deviations) of 4.6(0.5) and 4.4(1.2) respectively.  The painful stimulus was not rated as painful by the subjects but at a level of 3.2(1.8) by the controls.  Most importantly there were no differences on fMRI scanning between the groups with similar levels of activation seen in the thalamus, anterior cingulate gyrus, insula, and pain matrix as a whole.

The fMRI results of the pain matrix response in normal controls and patients who are congenitally unable perceive are extremely interesting.  Both groups had similar tactile sensation.  The authors suggest that caution must be used when interpreting the imaging of this pain matrix for studies looking at the treatment of chronic pain.  At another level, they seem like another addition to a long line of neuroimaging studies that do not seem to correlate very well with what they claim to represent.  An accompanying editorial by Geha and Waxman discusses the fact that the pain matrix has been validated in hundreds of studies using different nociceptive input.  They point out that some researchers equate activation of the pain matrix with the conscious perception of pain.  They review some of the evidence against the pain matrix argument.  One group has shown that activation of the pain matrix is multimodal.  They show how context (monotonous versus novel stimuli) and multisensory and multimodal processing is important.  These authors point out that they have shown fMRI activity in the pain matrix in chronic pain patients without any stimulus.  There cite a study that looks at how the pain matrix is activated in the subacute stages of chronic pain (6-12 weeks) and then as it becomes chronic at up to one year it shifts to emotional circuitry in the medial prefrontal cortex.  The authors also describe emotional and reward related decision making by the ventral striatum and medial prefrontal cortex, and how that activity decreases when chronic pain is successfully treated with carbamazepine while other areas of the pain matrix were unchanged.  Plasticity is also cited as being important both at the clinical level with some basic science support showing that hippocampal neurogenesis was necessary to develop chronic pain behavior in rodents.        

This research is extremely interesting at two levels.  The first is a possible route to quantitative assessments of chronic pain.  A lot of that will depend on a lot more data on the resting state of these brain systems and what changes can be consistently measured.  Having lived through the era of quantitative EEGs - I see too many similarities here to not be skeptical.  It is also not possible to do fMRI studies on chronic pain patients - there are just too many.  Like most psychiatric disorders we need a rapid, inexpensive marker that our patient likely has chronic pain and a measure of severity would be useful.  The second level is broadly important and that is figuring out how human consciousness occurs and how the individual conscious states of chronic pain patients differs.  

Until then - I will be paying close attention to the arguments for and against the pain matrix and research papers that use this description.


George Dawson, MD, DFAPA



References:

1:  Salomons TV, Iannetti GD, Liang M, Wood JN. The "Pain Matrix" in Pain-Free Individuals. JAMA Neurol 2016 Jun 1;73(6):755-6. doi: 10.1001/jamaneurol.2016.0653. PubMed PMID: 27111250.

2:   Geha P, Waxman SG. Pain Perception: Multiple Matrices or One? JAMA Neurol 2016 Jun 1;73(6):628-30. doi: 10.1001/jamaneurol.2016.0757. PubMed PMID: 27111104.

3: Tang Z, Chen Z, Tang B, Jiang H. Primary erythromelalgia: a review. Orphanet Journal of Rare Diseases. 2015;10:127. doi:10.1186/s13023-015-0347-1.

4:  Congenital Insensitivity To Pain (CIP).  Genetics Home Reference.  National Library of Medicine.  Link.

Attributions:

1:  From reference 2 above.  The figure is used with permission of the American Medical Association from JAMA Neurology per the above reference.  License Number 3897150095337;  License Date:
Jun 26, 2016

The Demise of the "5th Vital Sign"

The American Medical Association came out two days ago and said that they were dropping the pain as the fifth vital sign movement because it encouraged opioid overprescribing.  Even more interesting is that I did not get the news from the AMA (I am a 30 year member) but from the Pain News Network.  The only stories that I could Google the next day was about the AMA defending its position against attacks from pain societies and organizations who want to maintain what I would describe as a liberal approach to opioid prescribing as the best way to approach pain.  My term liberal is meant to connote a political position with no basis in science and the lack of science started in 1998 with the pain as a 5th vital sign approach.  In 1996, the President of the American Pain Society declared pain as the Fifth Vital Sign.  In the year 2000, the Joint Commission (then JCAHO) launched a pain initiative that described the 10 point pain scale as a "quantitative approach to pain."

I don't know if quantitative analysis is still a prerequisite for medical school, but this is a reason why it still should be.  In quantitative analysis, the task is to measure chemical concentrations accurately and reproducibly.  To use a quote from my old analytical chemistry text (1): "Qualitative analysis is concerned with what is present, quantitative analysis with how much is present."  The ability to do this is often a major part of the grade for that course.  Since the chemical composition in the samples are known - they should be determinable with precision.  In some cases, a lack of accuracy can reflect problems with the analytical technique if there are widespread variations in the results.  This is a true quantitative approach.  Asking a person to rate their pain on a 10-point scale is not.  Pain is a subjective experience influenced by a number of variables including whether the pain is acute or chronic, emotional state, the presence of an addiction, and personal biology affecting pain perception.  It is not a quantitative assessment.  It is as obvious as asking someone where they are on the 10-point  scale and being told they are a "14".  There are a lot of potential messages with that statement, but none of them involve an accurate measurement of pain.  A quantitative scale has no implicit meaning - it is supposed to be a known measurable quantity no matter what.

From a medical perspective, there is also no better example of the adverse consequences of widespread screening for a problem.  Chronic pain varies with age and other demographic factors.  Epidemiological surveys show widely variable numbers of people with chronic pain, but some suggest an average is about 25% of the population and 10% of the population with pain that has some secondary disability.  While there are no good ways to estimate the optimal amount of opioid needed to treat pain in a population, current data suggests that the US is the largest consumer of prescription opioid drugs in the world.  For example, the US has 5% of the world's population and Americans use 55% of the world's supply morphine and 37% of the world supply of fentanyl.  By contrast 80% of the world population uses 9.9% of the morphine and 19.7% of the world's fentanyl.    The United States is clearly at the top in terms of opioid consumption.

Clinical trials have also shown that opioids are moderately effective for some forms of chronic pain and no more effective than non-opioid medications.  The screening approach to chronic pain is clearly associated with overexposure to opioids, widespread availability of illicit sources of opioids, and an epidemic of overdose deaths.  The idea that rapid assessments can be made with rapid qualitative screening by anyone also eliminated pain specialists as gatekeepers in the decisions about who would receive treatment with opioids for chronic noncancer pain.

In the opening days since the AMA statement, it appears that political forces are lining up to maintain the status quo.  The idea that the AMA has to defend their position seems like pure rhetoric to me.  How about the American Pain Society defending the original statement in the context of everything that has happened since?  Despite defensive statements about how opioid prescribing was increasing before the position was adopted - the hard data suggests that it was associated with a major inflection point in opioid consumption in the USA.

The policy debate on this simple statement has far reaching effects for health policy in the United States.  At every level in today's health care system there are groups of managers/administrators who have set themselves up to monitor various measurements and hold somebody accountable.  I doubt that they know the difference between quantitative or qualitative measurements any more than the people who proposed that a subjective pain scale was somehow a quantitative measure.

I doubt that any one of them ever took a class in Quantitative Analytical Chemistry.



George Dawson, MD, DFAPA



References:

1:  James S. Fritz and George H. Schenk.  Quantitative Analytical Chemistry. Second Edition.  Copyright 1969 by Allyn and Bacon, Boston, p 3.



Attribution:

Pain scale graphic downloaded from Shutterstock per their standard license on June 29. 2016.

The Medical Cannabis Smorgasbord In Minnesota

I took in a CME course on Medical Cannabis: Clinical Applications and Evidence for Health Professionals on April 28, 2016 8 AM - 5 PM.  It was done as a collaboration between the University of Minnesota Center for Spirituality and Healing and The Minnesota Department of Health Office of Medical Cannabis.  Minnesota was the 22nd state to legislate a version of medical cannabis and this conference showcased the Minnesota version, the state and federal regulatory landscape, the available evidence to support the use of cannabis in certain conditions.  The politics of medical cannabis was also on display with viewpoints by some of the experts on the panel that represented scientific data, but also complementary approaches that had very little to do with science.

The Minnesota approach is an interesting one, because it may prove to provide the only cannabis products that offer a relatively standardized dose of tetrahydrocannabinol (THC), cannabidiol (CBD) or some combination.  In Minnesota there are two companies that are the exclusive providers of non-smokable cannabis products that are extracted from the entire plant - Leafline Labs and Minnesota Medical Solutions.  The extraction process is entirely carbon dioxide based and no hydrocarbons are used.  There are strict quality control measures.  There are no smokable or combustible cannabis products in the state.  According the statute, medical cannabis is available only as "oil, pill, vapor (oil or liquid but not dried leaves or plant form) or any other form approved by the commissioner excluding smoking".  These two companies supply state operated pharmacies that dispense only the cannabis products.  In order for a person to access these products they need to register with the state, pay a $200 annual fee, be certified as having an eligible condition by a physician who recommends rather than prescribes the product.  The patient discusses the actual product to be used with the pharmacist and pays for the product.  There are no insurance companies or state programs that pay for the cannabis.

The speakers at this venue were highly qualified.  Donald Abrams, MD is an adult oncologist with 32 years experience.  He gave lectures on "Medical Cannabis and the Endocannabinoid System" and "Clinical Applications of Cannabis: Cancer Care."  Both were highly informative.  He is one of the few people to access cannabis that is grown by NIDA (National Institute of Drug Abuse) and go through the regulatory maze that allows researchers to use it in clinical trials.  He discussed a concept that I had never heard of before called the entourage effect.  The entourage effect was defined as the benefits of using the whole cannabis plant rather than the more specific compounds.  The theory is that there are compounds in the broad mix that enhance the overall effect of the more active ingredients by both pharmacokinetic and pharmacodynamic effects.  He described this as one of the principles of Chinese medicine, which of course is not the allopathic medicine that we all practice in the US.  He emphasized the benefits of delivery as smoke or vapor rather than oral forms largely due to rapid onset of action and more rapid adjustment of the dose compared with oral forms.  He presented data to show that a particular volcano style vaporizer can consistently deliver therapeutic amounts of cannabis to the patient.  Once that was determined, that was the recommended delivery system for his patients.

Michael Bostwick, MD a Mayo Clinic psychiatrist gave two excellent presentations on "Medical Cannabis: Barriers, Myths, and Evidence" and "Medical Cannabis Statutes and the Role of the Federal Government".  One of the biases discussed by Dr. Bostwick in the seminar was the common observation that advocates see cannabis as a cure for everything when there is scant data that it is useful for the indicated conditions.  Of course that bias may also reflect the mixed agenda of recreational cannabis advocates seeking to legitimize cannabis as medicine and open the door for eventual widespread legalization.  In that endeavor, science would be an expected casualty.  The other bias was hysteria over the adverse medical and societal effects of cannabis use and how at least some of those attitudes may have resulted from racist attitudes in the 1950s.  Images from Reefer Madness were shown, as being emblematic of the spirit of the times.  That exercise does have a much different meaning today.  A good portion of the audience was all seeing and all knowing - eager to laugh at the ignorance of this archaic movie and applaud any speaker who advocated for the removal of all barriers to medical (and non-medical) cannabis use.  The problem is that I was sitting in an audience watching Reefer Madness in 1973 who were acting the same way.  The bottom line is that, these biases have clear effects on legislation and that led to cannabis going from being listed on the US Pharmacopeia for a hundred years to Schedule I on the DEA list of Controlled Substances.  A countervailing fact is that cannabis has been around for 5,000 years and has no clear medical indication.  That was mentioned as a historical fact, but not as a potential rationale for the Schedule I listing.  There was plenty of optimism that the discovery of the endocannabinoid system and getting cannabis off the most restrictive controlled substance category would lead to a whole new era of useful medicinal compounds.

Dr. Bostwick's discussion of the regulatory landscape of cannabis was superb.  I teach this subject myself and he was somehow aware of two more memos from the Justice Department than I was on the practical aspects of enforcing the Controlled Substances Act in the context of increasing legalization at the state level.  He described this as the states "going rogue" which I thought was humorous.  He also carefully laid out the FDA regulatory process and how it is not really set up the approval of botanicals or researchers interested in using cannabis for research purposes.

Ilo Leppik, MD is a long time neurologist and epileptologist in the Twin Cities.  Thirty three years ago when I was an intern on one of the neurology services in town and he was an attending physician.  At about that time, he noticed some basic science research about CBD having potential anticonvulsant properties.  He tried unsuccessfully to get pharmaceutical companies interested in this compound for years.  He discussed the currently available research and the single company that is trying to get FDA approval for a cannabis derived approach to treating seizures.  He is also an advocate for getting all of his neurological colleagues involved as registered certifiers of medical cannabis.  Epileptologists treat refractory seizure disorders that do not adequately respond to other measures and in this population Dr. Leppik would use medical cannabis and he presented the supporting data.

 The well known publicized case of the pediatric patient with seizures was discussed by Dr. Leppik.  This case is frequently cited by pro-cannabis advocates as proof that cannabis is a legitimate medication that needs broader use.  He pointed out that this patient not only did not have the seizure disorder that he was purported to have (Dravet Syndrome) but that he also had not seen the top epileptologist in the state where he resided.  He went on to present a case from his own practice where childhood epilepsy was misdiagnosed.  He made the correct diagnosis, but at that point, the patient's mother insisted that he stay on CBD along with the correct anticonvulsant for the condition.  The patient eventually ran out of the CBD, but the seizures remained in remission because he had been put on the correct standard anticonvulsant for the correct diagnosis - in this case valproate.

Angela Birnbaum, PhD is a pharmacologist and presented the most science of the day.  Straightforward pharmacokinetic principles and how they apply to treating patients with epilepsy.  Her approach also highlighted the advantages of using the Minnesota approach to medical cannabis and being the only way to assure steady levels of the drug necessary to treat epilepsy.  Dr. Birnbaum also presented a graphic similar to the one below on the product types available from the Minnesota companies.  More detailed information is available at the company web sites shown above.

Susan Sencer, MD presented medical cannabis from the perspective of a pediatric oncologist.  With the relatively new medical cannabis laws in Minnesota, her pediatric hospital has certified its use in 19 pediatric patients all with cancer diagnoses.          

To a guy who has been an acute care psychiatrist and an addiction psychiatrist all of his working life, there were clearly some biases operating at this conference that very few people seemed to be aware of.  Cannabis was discussed as a nearly benign product.  Sure we know the endocannabinoid system has something to do with brain development, and sure it could lead to psychosis and early onset of psychosis but probably only in people who were predisposed to psychosis.  There were remarks that none of the panelists who recommended medical cannabis and followed adult patients on that cannabis had ever seen any of them develop an acute psychosis.  There were jokes made about the implausibility of amotivational syndrome.  In the opinion of the panelists side effects were generally benign, even though data was presented from clinical trials suggesting otherwise.  As I looked at the clinicians represented on the panel who treated patients with cannabis there were two oncologists, a neurologist, and a psychiatrist who specialized in treating chronic pain.  Only the psychiatrist talked about treating some people with psychotic disorders and at one point there was a slide that suggested chronic psychotic disorders might be a contraindication to the use of cannabis.  The data presented and the description of the practices suggested to me that there was a strong selection bias present.  The panelists were not seeing psychiatric complications or problems with addictions because they weren't treating anyone with psychiatric disorders or addictions.  Guys like me see those patients and the last thing we want to see is somebody giving our patients cannabis.  I think that it will be a much different story if the list of eligible conditions is expanded to include insomnia, anxiety, depression, and posttraumatic stress disorder like it is in some states and the list of medical personnel authorized to certify the use of medical cannabis expands.  Just expanding the indication to chronic pain will bring in a patient population that is probably distinctly different from the patient base that the panelists are treating.

As I have written on this blog many times before, I don't like the idea of medical cannabis for the exact same reason that one of the panelists mentioned - it always has been a political manipulation for the legalization of recreational marijuana.  If you want to advocate for the legalization of recreational marijuana that is fine with me, but don't drag physicians into it and pretend it is an allopathic medicine.  That reference came out at the conference many times when it was referred to as a "botanical" and therefore very awkward in the FDA regulatory scheme.  At the same time, I have no problem with oncologists or neurologists telling their patients to use it.  But I am not going to pretend that there is not significant psychiatric morbidity that extends far beyond activating psychosis in those who are predisposed.  And I imagine that many of my colleagues will find this out when they discover that some of their patients now have cannabis added to their list of medications and that many of the panelists will discover this if they start seeing significant numbers of patients with psychiatric problems and addictions.

Despite all of the politics and bias - there is some underlying science that supports medical cannabis and Minnesota has the most rational approach toward implementing it.  Addiction and the psychiatric side effects of these compounds will always be a limiting factor for some.   In that case - as in the case of every other addicting medication - the best solution is to avoid it and try something else.


George Dawson, MD, DFAPA

References:

1: Bostwick JM. We need to reschedule cannabis. A sane solution to an irrational standoff. Minn Med. 2014 Apr;97(4):36-7. PubMed PMID: 24868930.

2: Bostwick JM. The use of cannabis for management of chronic pain. Gen Hosp Psychiatry. 2014 Jan-Feb;36(1):2-3. doi: 10.1016/j.genhosppsych.2013.08.004. Epub 2013 Oct 1. PubMed PMID: 24091257. 

3: Bostwick JM, Reisfield GM, DuPont RL. Clinical decisions. Medicinal use of marijuana. N Engl J Med. 2013 Feb 28;368(9):866-8. doi: 10.1056/NEJMclde1300970. Epub 2013 Feb 20. PubMed PMID: 23425133. 

4: Bostwick JM. Blurred boundaries: the therapeutics and politics of medical marijuana. Mayo Clin Proc. 2012 Feb;87(2):172-86. doi: 10.1016/j.mayocp.2011.10.003. Review. PubMed PMID: 22305029; PubMed Central PMCID: PMC3538401.

5: Abrams DI, Guzman M. Cannabis in cancer care. Clin Pharmacol Ther. 2015 Jun;97(6):575-86. doi: 10.1002/cpt.108. Epub 2015 Apr 17. Review. PubMed PMID: 25777363. 

6: Hazekamp A, Ware MA, Muller-Vahl KR, Abrams D, Grotenhermen F. The medicinal use of cannabis and cannabinoids--an international cross-sectional survey on administration forms. J Psychoactive Drugs. 2013 Jul-Aug;45(3):199-210. PubMed PMID: 24175484. 

7: Abrams DI, Couey P, Shade SB, Kelly ME, Benowitz NL. Cannabinoid-opioid interaction in chronic pain. Clin Pharmacol Ther. 2011 Dec;90(6):844-51. doi: 10.1038/clpt.2011.188. Epub 2011 Nov 2. PubMed PMID: 22048225. 

8: Carter GT, Flanagan AM, Earleywine M, Abrams DI, Aggarwal SK, Grinspoon L. Cannabis in palliative medicine: improving care and reducing opioid-related morbidity. Am J Hosp Palliat Care. 2011 Aug;28(5):297-303. doi: 10.1177/1049909111402318. Epub 2011 Mar 28. Review. PubMed PMID: 21444324. 

9: Abrams DI, Vizoso HP, Shade SB, Jay C, Kelly ME, Benowitz NL. Vaporization as a smokeless cannabis delivery system: a pilot study. Clin Pharmacol Ther. 2007 Nov;82(5):572-8. Epub 2007 Apr 11. PubMed PMID: 17429350. 

10: Abrams DI, Jay CA, Shade SB, Vizoso H, Reda H, Press S, Kelly ME, Rowbotham MC, Petersen KL. Cannabis in painful HIV-associated sensory neuropathy: a randomized placebo-controlled trial. Neurology. 2007 Feb 13;68(7):515-21. PubMed PMID: 17296917. 

11: Carter GT, Weydt P, Kyashna-Tocha M, Abrams DI. Medicinal cannabis: rational guidelines for dosing. IDrugs. 2004 May;7(5):464-70. Review. PubMed PMID: 15154108. 

12: Andreae MH, Carter GM, Shaparin N, Suslov K, Ellis RJ, Ware MA, Abrams DI, Prasad H, Wilsey B, Indyk D, Johnson M, Sacks HS. Inhaled Cannabis for Chronic Neuropathic Pain: A Meta-analysis of Individual Patient Data. J Pain. 2015 Dec;16(12):1221-32. doi: 10.1016/j.jpain.2015.07.009. Epub 2015 Sep 9. PubMed PMID: 26362106; PubMed Central PMCID: PMC4666747.

13: Arneson T. Insights from a Review of Medical Cannabis Clinical Trials. Minn Med. 2015 Jun;98(6):40-2. Review. PubMed PMID: 26168662.

14:  Health Canada web page consumer information on cannabis.

15:  Health Canada Information for Health Care Professionals Cannabis (marihuana, marijuana) and the cannabinoids - a very highly regarded report by the panelists at this conference.  This is the 2013 version and a 2016 update is pending at this time.

16: Katona I. Cannabis and Endocannabinoid Signaling in Epilepsy. Handb Exp Pharmacol. 2015;231:285-316. doi: 10.1007/978-3-319-20825-1_10. Review. PubMed PMID: 26408165. 

17: Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, Miller I, Flamini R, Wilfong A, Filloux F, Wong M, Tilton N, Bruno P, Bluvstein J, Hedlund J, Kamens R, Maclean J, Nangia S, Singhal NS, Wilson CA, Patel A, Cilio MR. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016 Mar;15(3):270-8. doi: 10.1016/S1474-4422(15)00379-8. Epub 2015 Dec 24. PubMed PMID: 26724101. 

18: Reddy DS, Golub VM. The Pharmacological Basis of Cannabis Therapy for Epilepsy. J Pharmacol Exp Ther. 2016 Apr;357(1):45-55. doi: 10.1124/jpet.115.230151. Epub 2016 Jan 19. PubMed PMID: 26787773. 

19: Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, Dor M, Lerman-Sagie T, Ben-Zeev B. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure. 2016 Feb;35:41-4. doi: 10.1016/j.seizure.2016.01.004. Epub 2016 Jan 6. PubMed PMID: 26800377. 

20: Blair RE, Deshpande LS, DeLorenzo RJ. Cannabinoids: is there a potential treatment role in epilepsy? Expert Opin Pharmacother. 2015;16(13):1911-4. Epub 2015 Aug 3. PubMed PMID: 26234319; PubMed Central PMCID: PMC4845642. 

21: Rosenberg EC, Tsien RW, Whalley BJ, Devinsky O. Cannabinoids and Epilepsy. Neurotherapeutics. 2015 Oct;12(4):747-68. doi: 10.1007/s13311-015-0375-5. PubMed PMID: 26282273; PubMed Central PMCID: PMC4604191. 

22: Kaur R, Ambwani SR, Singh S. ENDOCANNABINOID SYSTEM: A multi-facet therapeutic target. Curr Clin Pharmacol. 2016 Apr 17. [Epub ahead of print] PubMed PMID: 27086601. 

23: Leo A, Russo E, Elia M. Cannabidiol and epilepsy: Rationale and therapeutic potential. Pharmacol Res. 2016 Mar 11;107:85-92. doi: 10.1016/j.phrs.2016.03.005. [Epub ahead of print] PubMed PMID: 26976797.

24:  Volkow ND, Baler RD, Compton WM, Weiss SRB.  Adverse Health Effects of Marijuana Use.  N Engl J Med 2014; 370:2219-2227,  June 5, 2014;  DOI: 10.1056/NEJMra1402309

Supplementary 1: At this time (Saturday afternoon) - I am still waiting for the link to all of the presentations.  I do plan to add some detailed information at that point - the above information was only what I can recall from direct observation.  As soon as I have those links I will be able to list the actual medical cannabis products in Minnesota.  They are not available on the Medical Cannabis web site or one the sites of either of the manufacturers.  Stay tuned for a graphic containing all of that information.

Supplementary 2:  One of the jokes about addiction specialists at the conference was that they were like "orthopedic surgeons at the bottom of a ski hill."  The obvious implication is that they only see the train wrecks.  The other implication is that non-addiction specialists can prescribe addictive drugs with with no concerns about addiction and they will usually be OK - that is most people will make it safely to the bottom of the ski hill.  Of course by that time they had already presented data that "only" 9% of people who use cannabis get addicted to it, they are almost all young, and the panelists general impressions that their patients did not have a problem with addiction.  There has never been any disagreement that in terminally ill patients - addiction is not a concern.  Chronic pain patients without a terminal illness have a much different problem.   The ethical problem to me is that there may be an obligation to make sure that the skiers can negotiate the hill before you sell them the ticket.  There is also a recent precedent for declaring that prescribing practices were too conservative based on addiction risk.  That happened right before the current prescription opioid epidemic based on seriously flawed studies of addiction.

Supplementary 3:  If you want the best single reference on this subject - go to the Health Canada monograph (reference 15 above).  Read the currently available document and wait for the 2016 update.  It is a free download.

Supplementary 4:  Marijuana and Cannabinoids - an NIH sponsored neuroscience summit; March 22-23, 2016.  Link to the archived video recordings.

Johnny Cash On Doctors And Chronic Pain

Driving home on a Friday night, as usual I am listening to public radio.  This time I happened to catch an interview with the late Johnny Cash.  Many people are not familiar with how much pain he endured over the course of his life, especially toward the end.  His problems with drug addiction are better known and that combination of chronic pain and drug addiction is a dangerous one.   I found a photo of Cash on Flickr that was taken by a photographer who encountered him when he had significant pain and I am currently trying to get permission to post that photo at the top of this essay.  The years of pain and illness appear to have taken a toll in this portrait and he looks weary.  I heard him commenting in a radio interview on the PBS series Blank on Blank.  After and introduction that describes him as having severe constant pain in his left jaw and the statement that he cannot take pain medications, the interviewer Barney Hoskins suggests that he is brave and Cash replies (1):

Johnny Cash: "No. I’m not very brave because for five years I didn’t try to take the pain.  I fought it.  I had a total of 34 surgical procedures on my left jaw.  Every doctor I’ve been to knows what to do next, too.  To relieve me of pain, I don’t believe any of them.  I’m handling it.  It’s my pain.  I’m not being brave either.  I’m not brave at all after what I’ve been through, I just know how to handle it."

That is hard fought wisdom when it comes to dealing with chronic pain.  In the previous few lines Cash had explained why he could not take pain medications.  He described it being like an alcoholic not being able to drink alcohol.  His pain started when his jaw fractured during a dental procedure and never healed appropriately.  In Hilburn's biography (2), Merle Haggard is quoted as saying that Cash was at a chronic 8/10 level, using the typical 10 point pain scale for the last 8 years of his life.  It is difficult to imagine how hard it might be to try to sing with chronic jaw pain.

Managing chronic pain in a person with a significant addiction problem is one of the most challenging areas of medicine.   For the past 15 years, the USA has been in the midst of an epidemic of opioid painkiller use and accidental overdose deaths.  This has been largely due to the effects of the politicalization of pain and pain medications starting with initiatives to prescribe more opioid pain medications for chronic pain and for acute indications that previously may not have resulted in that kind of a prescription.  From what I can tell, the liberalization of opioid prescribing came about initially as the result of initiatives from the Joint Commission (JCAHO), the Veteran's Administration, and the American Pain Society.  The initiatives can be viewed on this timeline. 

The treatment of chronic pain is also viewed as a treatment that involves multiple modalities.  It can certainly involve the use of various forms of pain medication, but physical therapy and psychological therapies are also mainstays of treatment.  I have consulted in many situations where patients have had multiple surgical interventions for pain that have not been effective.  I have never seen a person with 34 surgical procedures for the same pain.   From a purely medical perspective, the treatment can involve opioid medications, but also gabapentin, pregabalin, and various antidepressants.  Chronic pain is frequently associated with insomnia, anxiety, and depression and additional medical or psychological interventions for these problems is useful.  Many people have strong biases about opioid medications and consider them to be the ultimate treatment for pain.  Double blind, placebo controlled studies show that for neuropathic pain, the relief is moderate and generally equivalent to non-opioids.  Unfortunately for many, that fact is not known until after the person has become addicted to the opioid.

The surgical approach to pain is gradually changing over time.  I did a lot of neurosurgery during medical school rotations and in those days, there was a definite prosurgical approach to back and neck pain.  Imaging studies were more primitive with a predominance of CT versus MRI imaging of the spine.  I observed a lot of laminectomies and posterolateral fusions, using bone graft from a rib or iliac crest.  I was also in the clinic and saw large numbers of patients coming back over time for chronic opioid prescriptions for continued pain that failed to clear up with the operative procedure.  Our standard prescription in those days was Darvocet N-100s,  a fairly low potency opioid analgesic that also contained acetaminophen.  It was voluntarily withdrawn from the market by the manufacturer in 2010 after this labeling revision by the FDA in 2009 highlighting the risk of overdose, cardiac conduction abnormalities and fatal arrhythmias.  In the course of psychiatric practice, I pay close attention to spinal problems.  Spinal injuries are surprisingly common.  Degenerative disease of the spine is also common and there is very little focus on spinal health and the prevention of these problems.  In the people I have seen over the years, good prognosis spinal surgery in terms of pain relief generally involves a well defined lesion and neurological deficit in addition to the acute pain.  Chronic unchanged pain is still an outcome after repeated surgery.  At that point the question becomes, is there any medication that will reduce the level of pain.   Some people will do well with chronic opioids, but the problem is that patients with addiction generally do worse and exposing more and more people to opioids is increasing the number of people with addictions.  SAMHSA suggests the algorithmic approach in Exhibit 3-1 (3) above.  The problem is that there is no good data for relapse, failure, or success rates after trying an opioid for chronic pain in a person with an addiction.  My experience suggests that relapse rates are very high and success rates are very low, but I am seeing a population with a very high rate of addictions
         

In the absence of any markers of opioid addiction liability or reliable interview approaches a conservative approach is required and an extremely cautious approach is required if the patient has a known addiction problem.  The comment on doctors by Johnny Cash is one that is best not forgotten.  One of the reasons that opioids are prescribed in the first place is that pain is chronic and refractory to usual treatments.  In some cases, years of trying multiple opioids and going through residential drug treatment centers has resulted in the perpetuation of chronic addiction and chronic pain.  The algorithm above suggests the appropriate course of action for patients with that problem.  They need to be tapered off the pain medication and typically maintain the medication is necessary.  In many cases there is a significant amount of pain relief and improved function by tapering and discontinuing the opioids.  In some cases, the ability to function improves because the addiction fades away even though the pain is no better.

Johnny Cash got to the point where he could be tapered off the opioids and make it on his own.   That is a tough goal, but one that more people should strive for at least until there is a better solution to chronic pain and addiction.  He also reminds us of the role of physicians in this process.  My overall impression is that there are more physicians willing to draw the line and say: "I really don't think that another operation or medication is going to add much to what you have already tried." ..... but I don't think there is a lot of evidence to back up my opinion.      

George Dawson, MD, DFAPA

References:

1:  Barney Hoskins.  Johnny Cash on the Gospel.  Blank On Blank.  October 1996. 

2:  Robert Hilburn.  Johnny Cash - The Life.  Little, Brown, and Company.  New York. 2013. 

3:  Substance Abuse and Mental Health Services Administration.  Managing Chronic Pain in Adults With or in Recovery From Substance Use Disorders.  Treatment Improvement Protocol (TIP) Series 54.  HHS Publication No. (SMA) 12-4671.  Rockville, MD: Substance Abuse and Mental Health Services Administration, 2011. (Figure 3-1 above is from page 34 of this manual).

Lessons From Physical Therapy

I remember the first time I experienced any significant knee pain.  My wife and I had just purchased an old house and as part of the sweat equity that young homeowners do we were going to refinish all of the hardwood floors ourselves.  If you have ever tried that, the most imposing part of the task is sanding all of the floors.  Hardwood floor sanders are very heavy pieces of equipment with cast iron bodies.  My first task was to carry this machine that I guess easily weighed over a hundred pounds up to a high second floor in our old house.  That was about 25 steps and a landing.  By the time I got to the top, it felt like both knees had bottomed out and were starting to creak.  At the time I was a competitive cyclist and training by putting in 200-250 miles on the roads and hills of Duluth, Minnesota.  I had never encountered this type of pain before during cycling, speedskating or weight lifting.   I compensated the best I could by taking the sander down just one step at a time and bringing it up and down again after we ruined the first staining attempt.  Eventually the pain went away, but I had learned several valuable lessons.  Cycling for example, did not cause any knee pain even after this acute injury.  I developed a strong preference for cycling and skating and decided to forget about running.

A couple of years went by and I developed some pain in my lateral knee.  I had already been diagnosed with gout in medical school and compared to gout pain most other musculoskeletal pain is minor.   My experience with physicians diagnosing gout was very mixed and I did not want to get a recommendation for medication if something else would work better.  Instead of seeing a primary care physician, I went in to see a physiatrist who happened to be a sports medicine doc.  He jerked my knee around and was satisfied it was stable and showed me some basic iliotibial band stretching exercises.   Within a week the pain was was gone.

My most foolhardy adventure in knee injuries was trying to extend my usual 40-50 miles training rides to 100 miles with no buildup.  I was out riding the roads in Washington County and remembered a theoretical 100 mile loop that I always wanted to ride.  It was a hot summer day, I felt very fast, and I had plenty of daylight so I took off.  At the 3/4 mark I was coming up a long steep grade and felt some left knee soreness that persisted the rest of the way.  My knee was burning when I stopped and I ignored it and did not ice it that night.  By morning I had developed a significant effusion and could not bend it.   I saw an orthopedic surgeon the next day who jerked my knee around, told me it was an overuse injury, and put my leg in a knee immobilizer.  Within two weeks I was out cycling again.

At other times I have allowed my body to get seriously out of whack.  After years of cycling I started to realize that I ended each session with severe neck and shoulder pain.  After numerous adjustments to the stem length on my bike, a physical therapist figured out I was was extending my neck too far to look up from my riding position and fixed the problem by modifications to my riding position and neck exercises.  At one point, I was almost exclusively cycling and got to the point it was painful to walk around the block.   The solution was again exercise modification and exercises to improve hip flexibility.  

All of this experience has led me to be very conscious of knees and other joints and keeping them in good working order as I age.  Not just my joints but the joints of my wife, family and friends.   It is kind of amazing to hear the emphasis on physical activity at all ages and yet there is no information out there on joint preservation or how to preserve your back.  Many people are surprised to learn that the circulation to intervertebral disks in the spinal column is gone at some point in the late 20s.  That makes biomechanics and muscle conditioning some of the most important aspects of joint and back function as you age.  It also makes physical therapy and exercise some of the most important tools to maintain musculoskeletal function with aging.   When I develop some kind of musculoskeletal pain, the first thing I do is call my physical therapist and schedule an appointment to see her.   She does an examination and an analysis of the biomechanics of the problem and tells me how to solve it.  I have been through the process many times with a physician and the main difference is that there is no biomechanical assessment, no actual manipulation at the time that may be useful, and no specific exercise program to make it go away and stay away.

The results of a medical evaluation are as predictable.  You have a diagnosis of muscle or joint strain.  Use ice or heat whichever one makes you feel better.  I have been told by rheumatologists that there is really no scientific basis for the heat versus ice recommendation only the subjective response.  And of course the recommendation for NSAIDs (non-steroidal anti-inflammatory drugs like ibuprofen) or acetaminophen.  I ignore the NSAID recommendations and take as few tablets of naproxen every year as I can.  I consider NSAIDs to be highly toxic drugs and avoid them even though they are effective.  I had a rheumatologist at a famous clinic tell me that the best evidence that NSAIDs were effective was the negligible amount of joint cartilage that was left when patients came in for joint replacement therapy.   Strong evidence that NSAIDs could knock out the pain as the joint deteriorated.   The only time that I was ever offered an opioid was when I had my first gout attack.  I was seen in an emergency department for severe ankle pain and discharged with a bottle of acetaminophen with codeine - a medication that is totally useless for gout pain.

In clinical practice I see a lot of people with chronic pain.   I notice that many of them are taking NSAIDs on a chronic basis and experiencing complications of that therapy like renal insufficiency.   I notice that practically nobody sees a physical therapist.  I notice that many people are now started on oxycodone or hydrocodone for mild sprains and injuries involving much less tissue injury than many of the injuries I have sustained during sports.   There are also many people who do not receive adequate advice on modifying their activities once an injury or series of injuries has been sustained.   For example, should a person keep running if they have sore knees, are 30% overweight, and have radiographic and physical exam evidence of degenerative joint disease?  Many people seem to have the idea that they can just wear out joints and have them replaced and the replacements will be as good as new.   Some will decide that it is just time to hang it up and start to sit on the couch and watch television.  They are surprised that their pain worsens with months of inactivity.   Some of the patients with back pain decide: "This pain is so bad that physical therapy is not going to do anything.  I am going to get surgery as soon as I can."  The widespread ignorance and neglect of musculoskeletal health is mind boggling to me.

I got into an exchange with an orthopedic surgeon in our doctor's lounge one day - over lunch.  He wanted to talk about narcissistic personality disorder and I wanted to talk about the biomechanics of the knee and hip joints.  It was a lively exchange and in the end he agreed with me about the huge importance of biomechanics during physical activity and as a way to prevent injury and degenerative disease.  It turned out he just wanted to hear about the personality disorder and did not have an opinion on it one way or the other.

I teach a lot about central nervous system plasticity in a neurobiology course that I give several times a year to different audiences.  Widely defined, plasticity is experience dependent changes in the nervous system.  There are a number of mechanisms that can lead to these changes.  Kandel and others have pointed out that these are the mechanisms of animal learning.  Two examples jump out of those lectures.  The first is a physical therapy example of knee extension exercises in the treatment of knee injuries.  It has been known for some time that quadriceps strength and balance through the knee are critical factors in knee rehabilitation and the prevention of future injuries.  Research in this area shows that increased quadriceps strength can occur in the same session.  The other example I use is a guy who wants to go to the gym to increase the size of his biceps.  He starts doing curls and within 6 weeks his strength has increased by 25% but there is no muscle hypertrophy.  His biceps diameter is unchanged.  What do these two examples have in common?

The common thread here is CNS plasticity and everything it allows us to do.  Plasticity will allow your to keep your joints healthy and relatively pain free if you allow it to.  You have to be willing to accept the idea that pain can come from deconditioning and biomechanical problems that are reversible by plastic mechanisms.  The only additional information needed is if it is safe to exercise and that can be provided by a physician and a physical therapist.

And the lesson for psychiatry?  Chronic pain patients certainly need to hear this information especially if they are deconditioned.   People addicted to opioid pain medications who are not getting any relief need to hear this information.  Patients in general with exercise modifiable conditions who see psychiatrists need to hear this message.  There is also a lesson for psychotherapy no matter how it is delivered.  Kandel's original example of plasticity was a psychotherapy session.  If your brain is modified by exercise there is no reason to think it can't be modified by anything from straightforward advice to more complicated therapies.   Success in that area can lead to the limited or no use of medications and a conscious focus on what is needed to maintain health like I discuss from my own experience.  I certainly don't take any medication for pain that physical therapy or exercise adequately treats.  The same argument can be applied to anxiety and depression that can be adequately addressed by psychotherapy or other psychological interventions.  On the other hand if most people don't know that physical therapy, exercise and activity modification successfully treats musculoskeletal pain and other problems they are unlikely to try.    


George Dawson, MD, DFAPA

Supplementary 1:  There are currently only 4 Medline references on biomechanics plasticity sports.  This seems like a promising area for sports medicine, physical therapy, and rehab medicine.

Supplementary 2:   The photo at the top of the page is an exercise I do to alleviate knee pain that I learned from the book The Knee Crisis Handbook by Brian Halpern, MD with Laura Tucker.  The exercise is called the quad set (p. 238) and although the author suggests a towel under the knee, I am doing it on a styrofoam roller.  This book contains a wealth of information on knee health.  I do not recommend doing what you see in the picture without reading the book.  I have no conflict of interests related to this book and purchased it online entirely for my education.

Supplementary 3:  I could not figure out where to fit it in above but after 25 years riding with 175 mm crankarms on my bike, I dropped them back to 172.5 mm.  The bike fit expert for my new bike was convinced it was a good thing to do.  My new bike rides so much differently it is difficult to know what to attribute to crankarm length.  

The Spine In Psychiatric Practice

I am not talking about the spine as a metaphor, I am talking about the real spine.  I am also not going to discuss some alternate therapies affecting the spine, I am going to refer to it only in the context of actual medical practice.  Maybe it was my interest in chronic pain and neurosurgery that led me to the observations, but many years ago I started to notice the high number of patients who were seeing me and had associated spine problems either associated with their psychiatric disorder or making it worse. As far as I can tell, this problem is really not well addressed in the psychiatric literature.

The spectrum of spinal disorder presentations varied from undiagnosed, to incorrectly diagnosed, to diagnosed and treated many times.  There is also the issue of how normal imaging studies vary greatly with age and eventually produce radiology reports that sound pathological but do not necessarily explain the observed pain or disability.  The usual psychiatric diagnoses included depression, anxiety, insomnia, and chronic pain.  The correct diagnoses were most often only possible by a detailed discussion of the problem.  In many cases the patients I was seeing had never actually seen a physician for back pain.  Let me illustrate with a couple of examples (none of these vignettes represent actual patients).

Patient A is a 35 year old woman being seen for depression.  She is in a stressful work situation because she is expected to be physically vigorous and move many 40 pound boxes of paper per day, but she is limited by neck pain and muscle atrophy in the left arm.  She injured her neck at a different job 5 years earlier lifting a heavy piece of equipment down from a shelf.  She felt immediate neck pain and over the next several weeks had muscle twitching in her left arm.  She did not have health insurance from her employer and was never assessed for the injury.  She has had daily pain since the injury and on days where she has more physical activity, she has more pain and more depression.  She is interested in treating the depression.

Patient B is a 50 year old man being seen for depression and insomnia.  He has a 5 year history of taking zolpidem for insomnia.  He is referred by his primary care physician because he has had to increase the dose of zolpidem to 20 mg/day because of worsening insomnia.  The patient gives a history of no longer being able to sleep on his right side because he has neck pain with radiation to the shoulder that resolves when he changes his sleeping position.  He has seen the Silenor and Lunesta commercials and is interested in changing his sleep medication.

Patient C is a 60 year old woman with a history of multiple upper and lower back procedures including fusions, discectomies, and foraminotomies.  She has also had surgical complications including infections and a cerebrospinal fluid leak.  She is taking oxycodone 40 mg QID with addition 5-10 mg prn doses of oxycodone.  She is also taking lorazepam 1 mg TID for anxiety and drinks wine on a daily basis.  She is referred for treatment of depression and chronic pain.

These three descriptions of patients highlight a number of problems unique to psychiatric practice.  Psychiatrists often see people with degenerative or traumatic changes to their spine that have never been assessed by a physician.  We also see patients who have had intensive surgical treatment and who have been treated in pain clinics for a long time before anyone thought to refer them to a psychiatrist.  In both cases an antidepressant seems to be a proxy for a psychiatric evaluation or an interview that seeks to determine if the spinal problem is a cause of depression, insomnia, or anxiety.  That type of evaluation is fairly straightforward but it does require time and the ability to do a medical and neurological review of systems and recognize common patterns of spinal syndromes.  The risks are minimal and the potential rewards are great for the patient.  I have had people ask me why I was asking them so many "medical" questions or report that their primary care physician wanted to know the same thing.   But I have also had people tell me that they were glad to know that they really had chronic pain from a fixable spinal problem rather than chronic insomnia and a need to take sleep medication forever.

This issue also highlights the issue of a physical exam in psychiatric practice.  When is it necessary and in what context can it be done?  In my first job I recall asking the clinic administrator whether she would provide a room and basic equipment for a physical exam.  She said that she would but in the three years I worked there it never happened.  If there is no adequate place to examine a patient I don't think an examination should be done.  There is also the question of the emotional relationship with the patient.  Many people seeing psychiatrists consider them to be their primary physician and have had many intense discussions with them over the years.  Psychiatrists should be aware of this emotional context and the meaning of any physical touch that occurs in that context and keep the assessment at the verbal level.  Referral to a physician who you know does a thorough neurological and spine exam is indicated for most cases, but in many cases you are seeing people referred from these physicians and it has already been done.  What about imaging studies?  My rule of thumb is to do them only if the patient has been physically examined.  I have physically examined people only in acute care settings and ordered imaging studies (CT and MRI) in that context.

On the positive side a lot can be done within the constraints outlined above, first and foremost is a detailed evaluation of the problem.  How is it that insomnia from neck pain can be treated for years as primary insomnia without any attention being paid to the cervical spine pain as being the likely source of that insomnia?  The only explanation I can come up with is a cursory evaluation of the pain.  Borrowing a page from Engel any psychiatric evaluation of a person with depression or anxiety, insomnia, and pain needs to be as comprehensive as possible.  The evolution of those problems since childhood and the relationship to physical and psychological trauma as well as other major life events needs to be detailed.  Assessing the patient for any possible addictions is another requirement.  A description of the pain and associated neurological symptoms is critical.  I like to review old records, imaging reports and the images themselves if possible.  There are a few of the highlights of what is necessary to come up with a psychiatric plan of care for people with spinal problems.  In many cases, a psychiatrist is the only person addressing their pain, even though they have a known diagnosis of degenerative disk disease and chronic back pain.  It is very useful to have referral patterns and treatment plans established to be able to offer treatment of the pain or associated spinal problem in addition to addressing the identified psychiatric syndrome.

The ability to help this group of patients also has training implications.  You don't learn about the spine, neurosurgery or neurology doing psychiatry rotations in medical school.  I was fortunate enough to have intensive exposure to these areas and to excellent clinicians.  I was also fortunate to work in a multispecialty clinic for 23 years where I had the benefit of discussing these cases with specialists from all fields.  I was also able to walk down to Radiology and discuss films with an excellent neuroradiologist.  The training suggested by Insel with a clinical neuroscience in psychiatry, neurology, and neurosurgery would enhance the evaluation of these problems. 

It pays to focus on both the central and peripheral nervous system when indicated.

George Dawson, MD, DFAPA

Treatment of chronic pain with opioids - back to the future

I thought I would wade in on this issue largely because I am not hearing a lot of rational discussion about the problem.  You might ask: "What does a psychiatrist know about this issue?" and the answer like most questions about psychiatry is "plenty".  I worked on a busy inpatient unit for 22 years and saw plenty of people with with severe chronic pain and episodic pain crises.  In that same facility, I also covered consults on medical and surgical patients many having problems with chronic pain and addiction.  As an addiction psychiatrist, I have talked with countless people who ran into problems with pain medications or relapsed to using another drug after being exposed to opiates for treatment of acute or chronic pain.  There seems to be very little reality based information out there to inform people about the risks and benefits of pain treatment with opiate medication.  The argument like most in our society is politically polarized to those who believe it is unconscionable to not treat pain even if it means a long course of opioids to those who believe that opioids are dangerous medications that should be conservatively prescribed.  So where does the truth lie?

I can tell you how it was in Minnesota in the 1990's.  There were very few pain specialists.  The wide spread prescription of opiate medications for chronic noncancer pain by generalists was uncommon.  In many cases if it seemed indicated, the generalist would refer their patient to a pain specialist who would provide them with a letter of agreement on the use of chronic opioids.  That all changed with a Joint Commission initiative on pain in 2000.  At least some authors see it that way and that was my experience.  Since then opioid prescriptions have been taking off with an associated increase in the production of these compounds.  This graphic from the CDC is instructive (click to enlarge).  The rates of increase of sales, deaths, and treatment admissions are all increasing at an astronomical rate relative to population growth.

The issue that is debated in the media and some government web sites is why is this happening and what is the best way to deal with it.  The FDA has recently incentivized drug manufacturers to come up with better tamper proof opioids.  The enforcement arm of the government is rigorously prosecuting some doctors.  The FDA has also initiated a course for doctors who prescribe opioids.  None of these measures addresses the core problems that were successfully addressed in Minnesota in the 1990s.  I will take a look at the specific issues involved:

1.  The genetics of opioid preference:   People at risk for abuse and addiction to opioids have intensely positive subjective experiences from taking opioids.  People not at risk have intensely negative experiences or the opioids make them physically ill.  We currently know nothing about the genetics of this response, but it makes sense to let patients know that if they do have an intensely positive response in terms of feeling euphoric or energetic that is not a good sign in terms of addiction potential.  It might even be reasonable to come up with a plan about what to do if that happens.  Seeing people back in a month who have no knowledge of this risk is probably not the best plan.  It is critical that there is a good therapeutic alliance between the patient and physician and that they are both focused on the full spectrum of problems.  

2.  The genetics of opioid response:  Individuals studies and reviews of studies generally show that a subset of patients respond to opioids.  There may be additional factors that should factor into patient selection such as the specific type of neuropathic pain.  The current concern and reaction to the opioid epidemic is based on the concept that opioid prescribing is a potentially high risk intervention.  If that is the case we need a better options for patient selection than a subjective report of pain.

3.  The public perception that opioids are the silver bullet of pain relief must be dispelled: This is the driving force behind escalating doses of opioids and the addition of benzodiazepines (an equally bad idea).  Excellent double blind placebo controlled studies of self titrated opioids in chronic neuropathic pain have showed moderate pain relief that is on par with non-opioid medication.

4.  Tolerance to analgesia and opioid induced hyperalgesia:  Education about these phenomena is needed because both lead to escalating doses of opioids.  The dose escalation may be appropriate, but in many cases the dose is increased with the goal of eradicating pain and that is an unrealistic goal.  In people who have analgesic induced hyperalgesia, they are often shocked that their pain improves with discontinuation of the opioids.

5.  Assessment of functional capacity is critical:  Functional capacity is the ability to function in daily life.  It must be carefully assessed in anyone who is on chronic opioid therapy.  At moderate doses and in combination with other pain medications opioids can impair coordination, cause excessive sedation, and lead to significant impairment in daily functioning.  This is a sign that the dose of the opioid may be too high and reducing the dose is indicated.

6.  A hierarchical approach to pain treatment is still necessary and is the most rational approach to reducing the current epidemic of excessive opioid prescriptions:  If the degree of pain relief across a population is the same, why not use the drug with the lowest abuse and overdose potential?  That was the default model in the 1990s in Minnesota.  The National Health Service in the United Kingdom has operationalized that as their current pathway for treating neuropathic pain in the algorithm below (click to enlarge).  Note that the medications with no abuse potential are at the entry levels in this diagram and that pain specialists are the gatekeepers for opioids.

  
Like most political debates the current debate about how to stop the epidemic of opioid overdoses ignores that fact that the problem may have originated with a political initiative in the first place.  Using the NICE algorithm to get us back to the Minnesota practice model of the 1990s is a logical solution.

George Dawson, MD, DFAPA


Rowbotham MC, Twilling L, Davies PS, Reisner L, Taylor K, Mohr D. Oral opioid therapy for chronic peripheral and central neuropathic pain. N Engl J Med. 2003 Mar 27;348(13):1223-32. PubMed PMID: 12660386.

National Institute for Health and Clinical Excellence. Neuropathic pain: the pharmacological management of neuropathic pain in adults in non-specialist settings. NHS. March 2010.

Supplementary 1:

The Care Pathway Graphic is copyrighted © National Institute for Health and Care Excellence (2010) and is posted based on their allowance for reproduction for educational and not-for-profit purposes.  See their updated and revised guideline at: http://www.nice.org.uk/nicemedia/live/14301/65782/65782.pdf