Marketing, Advertising, and Safeguarding Objectivity

blame (third-person singular simple present blames, present participle blaming, simple past and past participle blamed)

1.     To censure (someone or something); to criticize.  [quotations ▼]

2.     (obsolete) To bring into disrepute.  [quotations ▼]

3.     (transitive, usually followed by "for") To assert or consider that someone is the cause of something negative; to place blame, to attribute responsibility (for something negative or for doing something negative).

To provide context for this post, I refer any interested readers to the previous post and the comment by Steven Reidbord, MD.  I started typing up a response and decided to just continue it into this post.  I like to post things in regular blog format, because the comment section is uneditable and I make frequent spelling and grammatical errors.  My intent is to provide my perspective rather than disprove any of Dr. Reidbord’s points which are basically critical points about assigning blame, the standard of proof that physicians are affected by marketing and advertising, assertions about the connection between all of the marketing components and the profits of pharmaceutical companies and the need for physicians to “safeguard” their objectivity.

On the issue of blaming Big Pharma, of course they have done all of those things.  I would expect them to because that is typical behavior of corporations.   There are some people that believe this indicates that all corporations are evil.  There is also a blanket level of condemnation of the industry independent of any specific legal charge or incident.  You can certainly find rhetoric against all industrial sectors.  Nobody seems to acknowledge that governments have developed this landscape, including a regulatory landscape that encourages individuals to take risks without worrying about any personal or criminal penalty.  Litigation for large corporations is seen as the cost of doing business.   It seems that if anything, the law is written to incur legal activity and legal fees.  It is probably no accident that most lawmakers are attorneys.   I am no more outraged about Big Pharma corporate behavior than I am about any other industry. 

Before anyone tells me that medical industries are somehow different because they deal with peoples’ lives, if you think about it numerous industries deal with peoples’ lives.  Some are actually toxic to peoples’ lives.  Others  (like medicine) have affiliated professionals with professional responsibilities but unlike physicians those professionals (who also work with industry and receive benefits from the industry) are seldom scapegoated because of it. 

On the issue of marketing, I have made the same arguments that Dr. Reidbord makes to Big Pharma critics for at least a decade.  I am usually met with the response that physicians have a higher calling and that we must somehow place ourselves above advertising so that we are not commercially influenced.  The corollary is all of the “proof” that advertising and marketing influences purchasing and therefore prescribing behavior.  There are many problems with the analogy and that argument.  First, the proof generally refers to a fairly loose body of literature with poorly stated hypotheses and experimental designs that are either nonexistent or inferior to any clinical trial designed by Big Pharma.  I am happy to entertain any evidence for this connection in the event that I have missed something.   Apart from lack of the experimental evidence, it defies common sense.  I am unaware of any multi-billion dollar product-based industry that thrives on advertising an inferior product and not backing it up with anything.  To use the automotive example, if I unwittingly purchase a Toyota based solely on a flashy ad and discover it is a lemon, I may conclude that this is an aberrancy or that all Toyotas are lemons.  Either way they are unlikely to find me as a future customer.   That is not a sustainable business model.  The general assumption about pharmaceuticals is that physicians don’t seem to be able to self-correct by noting deficiencies including a lack of efficacy during hundreds or thousands of prescriptions.  I find that to be much more likely that noting your car is a lemon.  With prescriptions physicians are professionally accountable to purchasers.  That is a higher standard than losing time or money on a car.  Second, if I respond to marketing and go down to my car dealer for a $500 cash rebate, 0% financing, or some other incentive, I will not be placed in some national database that can be used to suggest that I am morally inferior to physicians who are not in that database.  Oh sure,  there will always be the usual disclaimers that being listed in the database is really an appearance of conflict of interest rather than actual conflict of interest, but the implication of wrongdoing is palpable and usually evident by what is being written about this list.  Third, the reality of a general lack of effective medications is never really acknowledged.  I have never seen a study about marketing pharmaceuticals that takes that into account.  It is common in clinical practice even before the advent of DTC advertising to see patients who were desperate to try the next new drug on the market.  In many cases we are still looking for a reliable car in a field of Yugos.  We are not looking for a Corvette.  Does that mean we have been influenced by advertising?  Does that mean that the patient/consumer has been influenced by DTC advertising?  It may simply mean that we are faced with a large number of drugs with a lack of uniform efficacy and significant toxicities.  Fourth, there is an overgeneralization of an imaginary boundary problem between pharmaceutical companies and physicians that seems to flow from the marketing rhetoric.  Suddenly companies are not only marketing drugs, they are selling medical diagnoses and treatment guidelines.  Managed care companies and PBMs get a complete pass on this issue and the idea is that the Big Pharma-Physician alliance is in lock step to sell as many drugs as possible.  That is a rather pathetic characterization of the problem and the pat solution of cutting all industry ties is an equally pathetic pseudosolution.   I do consider the business end of Big Pharma to be marketing and advertising.  I think the effect of that marketing and advertising is a vastly overstated political argument.  I think it is hubris to imagine that physicians can’t self correct in the way that any consumer self corrects when purchasing any advertised product.

With regard to what is necessary – like most criticism of Big Pharma nobody is ever really explicit about their meaning.  Practically all articles written about Big Pharma marketing/advertising tactics especially those that involve physicians imply that everyone in that chain of events is working to enhance the bottom line of the pharmaceutical company.  Working for the monied interest of a pharmaceutical company is the conflict in conflict of interest. If you are asking the question: “Who said this was necessary?” I guess my answer would be; “Just about everybody.”

The last question that I hope to address is the idea of “safeguarding” one’s objectivity.  In the previous response the idea was that the physician psyche is so frail and easily persuaded that we need to avoid all contact with Big Pharma advertising.  If that is the case there are many other sources of discordant special interest information that we should avoid like the plague including less competent attending physicians and colleagues, less dynamic medical school lecturers, all forms of managed care, most hospital and clinic administrators, most media outlets and most federal regulations on billing, coding, and documentation.  Off the top of my head I could add previous standard medical practices like the Swan Ganz catheter,  massive back surgeries for back and neck pain, chronic high dose prednisone for COPD,  and meperidine injections for migraines.  The list is endless.

If my objectivity was that tenuous I would be sitting in a dark room somewhere practicing psychiatry the way it is described in the New York Times.   I would be depending on a blog or pious journal editors to keep me honest!  
   

I have no conflict of interest to declare.  I have rigorously avoided Big Pharma advertising and detailing long before it was fashionable to do so.  My interest in avoiding Big Pharma advertising was that I found it to be disruptive, annoying, and demeaning - largely to the reps seen lugging food up and down hospital and clinic hallways.  I will probably never consider myself too stupid to figure out advertising even at the purported mind-control levels.  If anyone reading this disclosure doubts this statement – feel free to look for my name in the database of corrupted (or not) physicians.
 

As a further point of disclosure, I drive a Toyota.  I have a general policy of driving a car until the 150,000-200,000 mile mark and then buying a new one.   I find that by that time most cars have multiple systems that start to fail and it becomes a long series of expensive repairs and safety problems.   I have been driving Toyotas for 10 years and that follows a long line of Chevrolet, AMC, Plymouth, and Pontiac products.  Irrespective of the advertising, my personal experience is that it is the most reliable and cost effective ride for the money. 

Those are my only interests in both Toyotas and new pharmaceuticals. 

  

George Dawson, MD, DFAPA

Supplementary 1:  Posted definition at the top is from Wiktionary per their open access agreement. I intended to use it here more as a graphic than text as a lead in to the article.  

Supplementary 2:  For anyone considering a post here as a comment - please consider composing your comment in a word processor and cutting and pasting it in here.  The comment section on Blogger is not a reliable area to compose and edit comments.  I have lost several myself and the text may be too small to edit.  If the comment appears to have been posted but it does not appear - please send me an e-mail.  It occasionally gets diverted to a spam folder and I can still retrieve and post. 

    

The Increasing High Cost of Generic Drugs

With all of the drama about high pharmaceutical drug prices, the marketing behavior of the Big Pharma biz, and the medicalization of American society - there has been very little said about the generic drug business.  I discussed it in this piece about the DSM-5 and an absurdly high anti-depressant profit attributed to the pharmaceutical industry.  One of the highlights was how inexpensive some of the most well researched and recommended  antidepressant drugs were.  Then just this weekend I got a call from a friend who was taking an antidepressant who told me that his cost went up by 25% on the medication he was taking on the same insurance plan.  As any psychiatrist knows it is practically impossible to advise a patient on what they will end up paying for an extended release version of venlafaxine, even though it has been generic for a while.  Any attempt to find out online results in a confusing blend of American and Canadian prices.  Some of the Canadian prices on the same list exceed what would be paid in the US.

I caught an article by Hirst, reproduced in my local paper this weekend.  She describes a patient who was taking generic carbamazepine.  Carbamazepine has been generic for years.  I can recall prescribing the generic 15 - 20 years ago for patients with bipolar disorder.  This patient had been taking the medication for epilepsy and getting the drug through Walgreen's Prescription Savings Club.  He was paying $20 for a three month supply, but recently the price increased to $100.  That forced him to buy it on a month to month basis.  My drug information suggests at least 5 generic manufacturers and the original name brand along with a sustained release patented version are all on the current market.  Senator Bernie Sanders (I-Vt) is quoted:  "....We wanted to know if there was a rational economic reason as to why patients saw these price increases or whether it was simply a question of greed?"  The federal government tightly regulates health care with special attention from the Department of Justice - how could dramatic price increases in the face of ample competition be a matter of greed?  Wouldn't there need to be a cooperative effort on the part of all competitors to drive up the prices that fast?  The article cites "raw material shortages, consolidation in the industry and medical advances that make replicating brand name drugs more expensive".  I don't accept that explanation any more than greed.  One of the most expensive medications to manufacture in recent times was atorvastatin.  When it first came out, I spoke to a scientists involved in the production and he told me what it cost per pill to manufacture.  That cost was a small fraction of the overall prescription price.  That leads me to believe that even a $4/month prescription for ranitidine can lead to profits for a generic manufacturer.

The Hirst article quotes a pharmacy benefit manager as saying that average cost of a generic drug prescription has increased from $14.21 in 2005 to $41.88 in 2009 and that 1/3 of available generics cost more than $100 per prescription.  Another consultant suggested that acquisition costs of pharmacies have increased 17,700% in the past year.

A more academic article is available from the New England Journal of Medicine by Alpern, et al.  Those authors look at the specific example of albendazole, a broad spectrum anti-parasitic with a long expired patent.  In 2010, the average wholesale price (AWP) for a single day dose was $5.92.  By 2013 it was $119.58.  The authors look at the National Drug Acquisition Costs file and cite a number of significant price increases in widely known generic drugs including captopril, clomipramine, digoxin, and doxycyline.  They have produced an excellent graphic that looks at the number of prescriptions and global Medicaid budget for mobendazole and albendazole and the factors that led to the significant price increases for the latter.  In this case it seems like a lack of competition as being the limiting factor and the authors cite that "drug shortages, supply disruptions, and consolidations within the generic drug industry" are all factors that decrease competition and therefore may increase prices.  They also described the generic drug approval process as slowing down competition especially in a market where a delay in implementation of the generic can cost additional tens to hundreds of millions of dollars.

Both the NEJM article and the Chicago tribune article have a supply side emphasis.  Adequate competition and innovation in a free market increasing supply and driving prices lower while maintaining high value to the consumers.  But there is another story.  Demand for pharmaceuticals is relatively inelastic.  That means that if there are price increases buyers cannot postpone their purchases for a better day without the risk of significant and in some cases life-threatening consequences.  That inelasticity is compounded by several recent factors that lead the further complications.   The first is the advent of high deductible health insurance plans.  The majority of employers use these plans largely because managed care has failed to contain costs and costs to their employees are generally shifted to that risk pool in the subsequent year.  This puts anyone with high deductibles at significant risk for out-of-pocket costs until that deductible is satisfied.  Any drug manufacturer can expect to receive significant out-of-pocket payments while the deductible applies.  The second is the advent of "tiered' coverage based on the insurance plan.  This usually involves a steeper copay for an insurance plan that covers less.  The real risk is that the patient may decide to simply forgo the prescription, but until that point is reached there is a good chance that they will pay significantly more than the lowest generic price in the drug class.  The current system of government sanctioned managed care and inelastic pharmaceutical demand places all Americans at financial risk since it is essentially a tax and in many ways an entitlement to health care companies including generic drug manufacturers.

The other obvious factor that none of the authors comment on is that some pharmaceuticals remain top selling drugs despite the fact that they are now generics.  In some cases like Advair Diskus, the drug is in a unique delivery system that is also patented.  Anyone using Advair is very likely to want to continue to use this delivery system whether or not it is a generic drug or not and the price remains high.  In another example from asthma care, numerous metered dose inhalers underwent a regulatory change in propellants from chlorofluorcarbons (CFCs) to hydrofluoralkanes (HFAs).  That was accompanies by a patent and an immediate and significant price hike to anyone using these inhalers.

I think that this trend is instructive for a number of reasons.  First, it illustrates that when it come to pricing of any pharmaceutical product it is more complex than just monopoly power.   There are clearly market forces in play that will escalate the prices of drugs that have been around well past the patent expiration date.  Conversely, there are many medications that have no pricing power and to the concern of patients and physicians they are just no longer manufactured.  It is easy to understand why generic drug manufacturers are unwilling to maintain a large inventory just so Wal-Mart and Walgreens can have a $4 per month formulary.  Second, it shows that there is a potential for significant distortion of markets being introduced by managed care  companies and their government counterparts.  Rather than the idealized "cost effectiveness" some of the arrangements out there are anything but cost effective and my example of how saving pharmacy costs can explode the cost of care in another direction is a case in point.

Most significantly, we have gone through a period of blaming the name brand pharmaceutical industry (otherwise known as Big Pharma) for a number of problems.  They have been blamed inadequate disclosure of clinical trials data, distortion of clinical trials data, ghost writing articles for physicians, and misleading marketing practices.  Critics also have the usual complaints about efficacy and side effects but seem to miss the regulatory goal of getting a relatively safe and effective (but not perfect) drug into the market for use.  They seem to get a pass  on their influence at the FDA and in fact, some critics seem to think that they can create an idealized regulatory agency that is free from political influence.  These critics seem to suspend the reality that pharmaceutical companies are businesses and that the people on the science end of those businesses in all likelihood have no idea about what is going on at the business end.  The explicit motivation according to the critics is money - the fuel of all businesses.  The generic drug industry (Little Pharma?) has a much smaller marketing infrastructure.  Research and development costs are much less.   They aren't detailing physicians. Until recently they were viewed as the saviors of the patient with little resources and a definite positive for every managed care company looking to enhance their bottom line by lower pharmacy costs.  They were the antidote to Big Pharma.  Despite all of the positive spin there has been a 300% price increase in 5 years for generic drugs.  I don't think I am going too far out on a limb here to say that generic albendazole may be one of the most profitable medications ever made.  Politicians are starting to make noise.  Can physicians be implicated like they were in the Big Pharma scandals? I don't see how, but nothing coming out of Washington would surprise me.

But the real silence here seems to be all of the Big Pharma critics.  We have a generic drug industry with no real explanation for huge price increases at least nothing we can easily attribute it to.  Instead of saying that Big Pharma unconsciously influences physicians into prescribing their expensive drugs, we have hundreds of thousands of physicians consciously trying to prescribe the least expensive drugs for their patients and they are now failing to do that on a regular basis.  Maybe the appearance of conflict of interest isn't quite the theory it was cracked up to be?

Where are the Pharmascolds with their theories?    


George Dawson, MD, DFAPA

Refs:

1.  Ellen Jean Hirst.  Generic drug prices skyrocket in past year:  They were supposed top be cheaper but market forces have intervened.  Chicago Tribune  11, 30, 2014.

2.  Alpern JD, Stauffer WM, Kesselheim AS. High-cost generic drugs--implicationsfor patients and policymakers. N Engl J Med. 2014 Nov 13;371(20):1859-62. doi: 10.1056/NEJMp1408376. PubMed PMID: 25390739.

3.  National Drug Acquisition Costs.  Page with multiple files.  This is a large document with over 600 pages and 20,000 medications listed by NDC number.  For a sample click on the graphic below and discover why aripiprazole (Abilify) is such an expensive medication.

How Do So Many People End Up on Stimulants?

There is no question that thousands if not millions of people end up taking stimulants unnecessarily these days.  Addiction psychiatrists,  have a unique perspective on this that I thinks goes beyond a typical approach to the problem.  I like to consider it to be grounded in behavioral pharmacology and neuroscience.   For the sake of this essay I will limit my remarks to all adults who are college aged or older and should not be taking stimulants.  Neuroscientific discoveries in the area of brain maturation suggest that a significant portion of the college-aged individuals might not make the same decisions they make a decade later, but the practical consideration is that there are millions of people in college making decisions about stimulants every day.  There are several ways to look at the problem.  The best approach I can think of is to look at the various ways that patients present for treatment.  The request for stimulant treatment can be subtle or overt.  Unlike some the papers in the current literature, I don't think that the diagnostic questions here are subtle.  During an initial clinical assessment - diagnosis and treatment commonly overlap and in some cases that I will illustrate treatment considerations become primary in the initial minutes of the interview.

The general psychiatric interview has always been a screen of sorts.  My recollection is that it was typically more problem focused in the past.  Over time, that interview started to incorporate more disorders as a focus of inquiry.  On the outpatient side the disorders added been primarily Post Traumatic Stress Disorder and Attention Deficit-Hyperactivity Disorder in non-geriatric populations.  Any time a screening is being done whether it uses a symptoms checklist or a lengthy interview there is always the chance of missing the true diagnosis or adding a diagnosis that is probably not there.  Here are a few examples.

1.  "I have been depressed for the past ten years...."  An inquiry about mood disorders at some point will focus on concentration.   Impaired concentration and attention span occurs in a number of psychiatric disorders.  Combined with some developmental history and a history of chronicity it is easy to see the problem as a missed diagnosis of ADHD and initiate treatment for that disorder in addition to the primary mood disorder.  There are problems with that approach especially when the history of the mood disorder is clear and it has never been adequately treated.

2.  "I have a diagnosis of bipolar disorder - manic and these medications aren't working...."  ADHD in adults rarely presents as hyperactivity so severe that it could be mistaken for mania.  Manic episodes are also phasic disturbances making it very unlikely that there would be many patients in any single practice who were both manic and had ADHD.  In the cases where it does happen stimulant treatment complicates the treatment of bipolar disorder and can lead to worsening mania, delusional thinking and hallucinations.

3.  "My son/daughter has ADHD....."  There are two variations in this interaction.  In the first, the parent is told about the high heritability of ADHD and advised that they also probably have it and can be assessed for it or mention to their primary care physician that they may need treatment for it.  In the second, the parent of a child with an ADHD diagnosis reads the diagnostic materials and comes into an appointment and says: "You know, I have read the symptoms and think that I have them.  Should I be treated for ADHD?"

4.  "I have always had a problem reading and I was  never any good in school..."  A common approach is to view this as ADHD, do the screening and proceed with treatment.  Physicians in general have had very little training in the assessment or treatment of learning disorder and although there is comorbid ADHD and learning disorders there is also a significant population of people with pure learning disorders who do not have ADHD.

5.  "I took my friend's Adderall and felt like I could concentrate and study for the first time in my life.  I did a lot better on that test...."  The population-wide bias is that stimulants are a specific treatment for ADHD rather than a drug that will temporarily improve anyone's energy level and attention span.  There is also the cultural phenomenon of cognitive enhancement or using stimulants as performance enhancing drugs that may be driving this request.  It is known that the availability of stimulants on campuses and in professional schools is widespread.  This is associated with students selling their prescriptions for profit and availability of stimulants illegally obtained for the purpose of cognitive enhancement.  The issue is further confused by position statements in scientific journals that support this practice.  I have not seen it studied, but it would be interesting to see questions and responses about cognitive enhancement asked at student health centers and practices that see a lot of college and professional students.

6.  "I have ADHD and need a prescription refill...."  It may be true that the patient has a clear-cut documented diagnosis prior to the age of 12 (DSM-5 criteria).  But what has happened since that initial diagnosis in childhood and now is critical history.  Has there been continuous treatment since then or has the treatment been disrupted.  Common causes of disruption include stimulant side effects, symptom resolution with age,  and co-occuring substance use problems.  A detailed history of the course of treatment since childhood is needed to make the decision to continue or reinitiate treatment.

7.  "I heard you had a test for ADHD...."  This question often initiates screening at a higher level.  There are any number of places with extended neuropsychological batteries, brain  imaging tests, or EEG tests that they claim will definitively diagnose ADHD.  In fact, there are no tests with that capability.  I have heard one of the top experts in the world on ADHD make that same statement and he was also a neuropsychologist.  I have had several years of experience with quantitative EEG machines and know their limitations.   At this point several hours of extended testing adds nothing to a detailed interview, review of collateral information, and symptom checklists to basically assure that all of the questions have been asked.

8.  "My meds need to be adjusted....."  This could be a question from a person in treatment for another problem or a person already being treated for ADHD.  The unstated issue here is the underlying belief that by adjusting a medication one's mental processes will be closer to perfection.  A child psychiatrist that I work with said it best:   "The goal in treating ADHD is to get them more functional, not to perfect their functioning."  I think the unrealistic goal of perfection drives a lot of prescriptions that exceed the recommended FDA limits.  It also explains a lot of "rescue medications" superimposed on sustained release preparations like Adderall.  Anyone familiar with the pharmacokinetics of sustained release drugs should realize why rescue medications (like immediate release Adderall on top of sustained release Adderall XR) are unnecessary.

9.  "I can't stay sober if I can't get treated for ADHD....."  This can be a complicated and confusing situation.  The child psychiatry literature had suggested initially that children with treated ADHD were less likely to have substance use disorders as adults than children with untreated ADHD.  As the evidence accumulates that is less clear.  Many adult psychiatrists and some addiction psychiatrists have extrapolated those equivocal findings to mean that treating a known or new diagnosis of ADHD in an adult will improve treatment outcomes for ADHD.  There is no evidence that is true.  Some addiction psychiatrists believe that the opposite is true, that there is a cross addiction phenomenon and that treating a person with an addiction makes it more difficult to stay sober from their drug of choice.  If the person is addicted to stimulant medication and has a clear history of accelerating the dose of stimulants or using them in unorthodox ways (intravenously, smoking, snorting, etc) it is very unlikely that person will be able to take a stimulant prescription in a controlled manner.  It is also very possible that the person making this request has a long history of experiencing prescription or street drugs as being necessary to regulate mental functioning.  That can be highly reinforcing even if the effects are sustained for hours or less.

10.  "I have been sober for one month and can't focus or remember anything......" Subjective cognitive problems are frequent during initial sobriety.  The substance used and total amount used over time probably determine the extent that the cognitive changes persist, but it is a difficult problem to study for those same reasons.  Clinicians know that there are cognitive effects but there is no standard approach to the problem.  From my experience, I think that two months sober is the absolute minimum time to consider evaluating subjective cognitive problems.  Even at that time getting collateral history about the person's cognitive and functional capacity and problem solving with them on work arounds would probably be the biggest part of the treatment.

The above scenarios are not exhaustive and I probably could come up with another 5 or 10 but they are illustrative of pathways to questionable stimulant use.  The common thread here is that anyone in these scenarios can endorse all of the symptoms of ADHD.  Figuring out what those symptoms are is fairly obvious on many checklists.  One of these checklists shows the symptoms and checkboxes necessary to make the diagnosis in grayed out panels.  It is easy to fake the symptoms in an interview or on a diagnostic checklist.  It takes a lot of hard work on the part of the physician to figure out not only who might be faking but also who has the symptoms but not the diagnosis.  One of the features of the DSM that was attacked by several critics during the pre-release hysteria was the "generic diagnostic criterion requiring distress or disability" to establish disorder thresholds (DSM-5 p 21).  In the case of ADHD that is Criterion D "There is clear evidence that the symptoms interfere with or reduce the quality of social, academic, or occupational functioning."  (DSM-5 p 60).

The diagnosis of ADHD is generally not the diagnosis of a severe functional disorder.  As a psychiatrist who practiced in a hospital setting most of the people I assessed clearly met the functional criteria by the time I saw them and diagnosed severe mood disorders, psychotic disorders, substance use disorders or dementias.   Many of them were by definition unable to function outside of a hospital setting.  It is an entirely different assessment when faced with a successful professional who has worked at a high degree of competence for 20 years who presents with any one of the above problems because they think they have ADHD.  It takes more than a review of the diagnostic criteria.   It takes an exploration of the patient's motivations for treatment.  What do they hope to accomplish by treatment?

It also takes a conservative prescribing bias on the part of the prescriber.  Stimulants are potent medications that can alter a person's state of consciousness.  They are potentially addicting medications and that can result in craving or wanting to take the medication irrespective of any therapeutic effect.  The wide availability of stimulants led to the first amphetamine epidemic in the United States.   When I first started out in psychiatry, I was still seeing people who became addicted to stimulants when they were widely prescribed for weight loss.   It is well known that the medications were ineffective for weight loss but people continued to take them at high doses in spite of the fact that they had not lost any weight.  In talking with people about what drives this many people feel like they are only competent when taking stimulants.   They believe that their cognitive and functional capacities are improved despite the fact that there is minimal evidence that this is occurring from their descriptions of what they are doing at work or in their family.

There are a number of strategies in clinical practice to avoid some of the problems with excessive stimulant prescriptions that I will address in a separate post.  My main point with this post was to look at some ways that people with mild subjective cognitive concerns, addictions, people seeking cognitive enhancement, people who have been functioning well but believe that they can function better come in to treatment for ADHD and get stimulant prescriptions.


George Dawson, MD, DFAPA

Supplementary 1:  Literature was used to construct these hypothetical scenarios.

Will The AI Apocalypse Be Worse Than Customer Service?

I am a survivalist and make no excuses for it.  I have posted my experiences in the cold weather and nearly freezing to death.  I am sure that is part of what makes a survivalist.  That combined with an early recognition that men often don't make rational decisions.   They are capable of making irrational decisions on a grand scale.  I was in grade school during the Cuban Missile Crisis.  Being in a small town, we escaped all of the duck and cover exercises that kids in the big city went through.  But paranoia about the Russians, nuclear war, and radioactive fallout was always there.  I worked for the town library in the 1970s and found out it had been the local nuclear fallout shelter.  I spent days clearing out steel 30 gallon drums that were supposed to double as water and waste containers in a fallout emergency.  In those days before atmospheric nuclear tests were banned, I can still recall a radioactive cloud passing over our town.  Experts from the state university were on television talking about Strontium-90 in the fallout and how that could end up in milk products.  My grandfather picked up on that and referred to it as "Strawberry-90".  He was somewhat of a radical, predicting that there was going to be a "revolution" at some point as the ultimate solution to a corrupt government.  Survivalism may have genetic determinants.

I was surprised when Stephen Hawking came out earlier this year and said that artificial intelligence (AI) represented a threat to humans.  I have seen all of the Terminator films and the Sarah Connor Chronicles.  As expected, any tales of a band of zealots surviving against all odds appeals to me.  But then it seemed that this was more than a cultural and artistic effort.  One of the arguments by Bostrom suggests that the survival of all of the animals on the planet depends on the animal with the highest intelligence - homo sapiens.  If a machine intelligence was developed one day that surpassed human intelligence it would follow that the fate of humans would depend on that machine intelligence.  There are competing arguments out there that suggest a model where the AI interests and human interests would compete politically.  Can you imagine how humans would fare in our current political systems?  A lot of the experts suggest that we won't have to imagine battling robots in human form and that makes sense.  It is clear that there are thousands of cyber attacks against our infrastructure every day.  Imagine what a concentrated AI presence unencumbered by sociopathy or patriotism could do?

Imagining the battlefield of the future scenes from any Terminator film or same-themed video game, I decided this morning that you don't need a high tech approach to wreak havoc among the populace and drain their resources.  You only need Customer Service.  The concept needs to be refined to modern customer service.  Even in the early days of the Internet, you could talk to a fellow human and they would hang in there with you until the problem was solved.  I can recall calling Gateway Computers for an out-of-the-box problem back in the 1990s.   The technical assistance rep and I completely disassembled and reassembled my PC over the next 2 hours.  And the end result was that it worked perfectly for the next 5 years.  I doubt that anything remotely that heroic happens today.

Twenty one days ago I downloaded graphics software from Amazon.   I am an Amazon Prime customer and order just about everything from them.  I am not a stockholder and my only interest is in getting things that nobody else stocks as soon as possible.  I had previously downloaded software from them and everything went well.  This time, I got an activation code and no serial number.  I complained to customer service and got an e-mail saying we will give you your money back but for the serial number problem you need to contact the manufacturer.  To back up a minute, I have no idea how I got that e-mail through to Amazon and could not replicate what I did in a hundred tries.  The obstructionist beauty that underlies all telephone queues and Internet sites is that it is very clear that they are not really designed to get you through to anyone.  It is a maze of dead ends and non answers.  At many of the dead ends you are polled: "Was this page helpful?".  So far I have not found a single page that was.

The dead ends at the computer graphics software site were even more formidable.  In order to contact customer service I had to set up an account.  After doing that I needed a serial number.   Of course that was my question in the first place.  How can I ask about getting a serial number when I need a serial number to ask the question?  It seemed like the ultimate dead end.  Amazon did send me a customer service number for the software company.  This number was not available on the company's web site.  In calling the number, their queue provided 4 options none of which applied to me.  It gave options for order numbers that started with different numbers and I had an Amazon number that did not fit any of the choices.  Just like my previous adventure in medical diagnostic queues - I picked one.  A scratchy recording of bad electronic music started playing.  It was interrupted every minute by a worse electronic voice telling me how important my call was and how I would be forwarded to a customer service rep.  That went on for half an hour and then the voice said:  "We are sorry but there is no one here to take your call.  Please leave a message with your number and we will get back to you?"

That was hours ago.  Given the attitude projected by this company, I am not holding my breath on the return call.  I have 1 week left to try to activate software that I paid over $400 for.  There is no solution in sight and it does not appear anyone is even interested in solving the problem, except me.  I can get my money back - but the whole point of this is that I really want to work with that software.

Implications for the AI Apocalypse?  It doesn't take much to defeat Internet dependent humans and deplete their resources.  I have actually taken PTO to try to accomplish this.

I don't think there will be a shot fired in the AI Apocalypse of the future.  No intense battles between humans and cyborgs.  No Doomsday Weapon.

 Just a low tech endless loop of customer service dead ends.


George Dawson, MD, DFAPA

Supplementary 1:   Photo credit here is FEMA.  It is an open access copyright free photo per their web site.

Supplementary 2:  My customer service problem was resolved today (on Tuesday November 25, 2014).  The final solution was given by Amazon and they deserve the credit for resolving this problem.  I don't think that detracts from noting the overall trend of decreasing support and what that implies for IT in healthcare and the culture in general.

How To Really Fix The Broken Mental Health System

A few weeks ago the Psychiatric Times posted an article called "How to Fix the Broken Mental Health System: Call For Suggestions."  I posted a link to one of my previous blogposts in the comments but decided to write a separate post here.  My reasons are several fold.  First off, any call for suggestions to me is really an invitation to generate web traffic to a particular site.  It is a standard tactic of bloggers.  For proof of that just Google the title and you will see hundreds of references in the last 2 years.  Second, I can do a better job and have done a better job here.  It gives me an opportunity to collect links under common themes.  Finally, it creates an opportunity to provide answers in one spot.  I may be wrong, but I think that the Psychiatric Times piece will be quickly forgotten.  Since hardly anyone reads this blog, that will probably also happen, but at least my thoughts are out there and include statements that you won't see posted by anybody else.   Here are  my point by point suggestions:

1.  Managed care and all that it involves including Accountable Care Organizations (ACOs), Pharmaceutical Benefit Managers (PBMs) and the Substance Abuse and Mental Health Services Administration (SAMHSA) must go.  It should be evident to anyone that these organizations have not contributed to cost effectiveness, innovation, quality or efficiency.  Instead they are largely responsible for an additional hidden tax on all Americans.  I am referring to the typical high deductible health insurance plans that results in thousands of dollars in copays and premiums before any health care has been received and the $250,000 in out of pocket costs that any 65 year old couple can expect to pay in additional health care costs.  Contrary to their advertising, managed care organizations disempower patients and their physicians and are the largest obstacle to care in this country.  Their disproportionate effect  on psychiatric and substance use disorder services has been well documented.

2.  Centers of excellence rather than collaborative care is the primary goal.  All of the managed care forces and their political backers in the first point above are making the argument that we cannot possibly produce enough psychiatrists to meet the need in this country.  They maintain that argument despite the fact that the US currently has about 1/4 the number of psychiatrists per capita as Switzerland, significantly fewer than 18 of 32 OECD countries, and is only 1 of 3 countries where the number of psychiatrists is decreasing.  Instead of developing a rational triage system, their solution has been to say that anyone can provide psychiatric services or that a psychiatrist reading screening checklists like the PHQ-9 is some kind of psychiatric care.   This is both an absurd characterization of psychiatry and a non-solution to the problem.  Psychiatric specialists need to be available to treat the most difficult to treat disorders.  They don't need to see everyone taking an antidepressant or everyone with insomnia.  They need to see people with difficult to diagnose problems and treatment resistant mood, anxiety, psychotic, neurocognitive, substance use, and psychotic disorders.   They need to see this population both for diagnostic clarification and treatment.  Centers of excellence need to be developed around these disorders and the associated treatment delivery.  There are current models that develop statewide systems of care around centers of excellence that seek to provide the highest quality of care to residents in that state.

3.  The administration of systems at the local level needs to be done from a clinical and not a financial point of view.  The split systems of care (administrative versus clinical) is one of many sources of poor quality care.   It has resulted in some situations as absurd as administrators believing that they can design systems of mental health care without input from clinicians.  This is especially problematic in treating patients who have  problems with aggression.  Psychiatric training needs to include specific instruction on how to clinically administer these systems of care.

4.  The psychiatric infrastructure needs to be rebuilt.  That includes both community and state hospitals.  Very clear criteria need to be established for admission to these facilities since state hospitals in recent times have been the only housing option for people with severe problems.  The concept of "treatability" has been inappropriately applied by federal regulators.  I worked for years as a Medicare reviewer and reviewed many state hospital records where I was asked whether or not the patient had achieved maximum benefit from hospitalization.  That would allow the administrative authority that I was working for at the time to deny any payment to the hospital from that point on.   The reality is that the patient was still severely disabled and could not live on their own, with their relatives, or in whatever residential facilities existed in the state.  Whether there was continued payment or not, there was no place to send the patient due to the presence of a chronic severe disorder.  That is still the problem today.  Rationing has resulted in a severely constricted infrastructure that does not match the needs of the patient population.  A state hospital system cannot exist in a vacuum.  There needs to be an established system of residential facilities apart from those hospitals that can accept people who may never acquire the skills to live in a group home setting or independently.

5.  An emphasis on independent living and competitive or supported employment needs to be the priority of any mental health system.  The community psychiatry movement introduced an important bias - that people with severe mental illnesses should always live independently rather than in an institution if possible.  That is a very important concept but it is time to move beyond that basic bias to a more comprehensive approach.  That includes not only the vocational rehabilitation aspects but a renewed emphasis on the cognitive and functional capacity aspects of severe mental illnesses.  We now have large detailed studies of cognitive deficits in groups of patients with schizophrenia, bipolar disorder and substance use disorders.  That knowledge has not been used to implement any innovative approaches to residential living or vocational rehabilitation.   Treatment rather than rehabilitative approaches to these deficits need continued emphasis and research.  The comprehensive treatment of any person with schizophrenia or a mood disorder should include an assessment of cognitive problems beyond the usual approach of treating symptoms.

6.  Increased availability of psychotherapy and case management services.  Medicalization has become a popular buzzword by journalists and critics of psychiatry.  If you ask any psychiatrist about the likely causes of increased prescribing and attempts to treat all problems with medications the likely response will be that there are no other resources left to treat the problems.  Many managed care systems have eliminated psychotherapists from their clinics or restricted access to available services.  Family and marital therapy is often not available at all.  Many counties have severely restricted the availability of placements for children with severe problems.   There are clear population based approaches that have not been implemented on a wide scale basis including computerized psychotherapy, brief cognitive behavioral therapies, mindfulness based therapies, basic behavioral approaches, and non-psychotherapy approaches like exercise.   These therapies can not only be applied to a wide variety of problems but also can be part of a rational triage system to reduce the prescription of medications and assure that psychiatrists are seeing only the most severe disorders.  This system would also be an asset to primary care physicians and provide them with viable options other than prescribing medications.

7.  Reform of the civil commitment process is necessary.  Civil commitment for involuntary treatment of mental illness and substance use problems is highly subjective and varies considerably from county to county within the same state.  That variance is largely due to variability in resources form county to county and interpretations of the statutes that generally are in line with the level of resources.  Civil commitment and associated legal functions such as conservatorship or guardianship can be life saving and life changing interventions.  A better infrastructure will give legal authorities more confidence that a viable intervention can be accomplished that will reverse the reasons why the person has entered the legal system.  But beyond that it has to be clear that managed care definitions of "dangerousness" and interpretations of "imminent dangerousness" are basically rationalizations to do nothing.  There also needs to be an avenue for preventing the incarceration of mentally ill and substance using patients for minor offenses and diverting them to treatment programs in the community.  Another area where legal interventions are critically needed is guardianship and conservatorship decisions for mentally ill patients in need of acute medical care.  Civil commitment, conservatorship, guardianship, and substitute decision makers all need to be rapid parallel processes done through the same probate court rather than different courts and different jurisdictions.  It is more likely that experienced judges and referees will be able to make better decisions.

8.  Better public health interventions for violence and aggression are needed.  There has been no progress in this area due to the political stalemate on gun control or gun access.  That never addresses the state of mind prior to the violent incident.  The necessary public health interventions need to come at that level and there needs to be centers where aggressive behavior can be addressed and treated before there are adverse outcomes.  Beyond that immediate need there is also very little dissemination of the information that is already known about childhood adversity and adult mental health outcomes.  There is so much critical information out there about the adverse impact of certain social experiences in childhood that are not public knowledge and that should be widely available.

9.   Pharmacovigilance and pharmacosurveillance services need to be developed in the same way that access to controlled substances prescriptions have been developed in many states.  We have been hearing about "Big Data".  Managed care systems have vast amounts of data that they consider to be proprietary that is analyzed from a business rather than clinical perspective.  Any clinician prescribing medications should get a monthly report on their prescribing patterns relative to all physicians and fellow specialists and subspecialists.  Statistical models of conservative prescribing and polypharmacy need to be developed.  Prescribing patterns associated with the highest complication rates need to be identified.   Feedback needs to occur at the level of the individual physician and the reports need an adequate amount of detail.  Literature based on data mining large PBM data bases is not useful to individual physicians.  With current pharmacy databases there is no reason why this system can not be developed nationwide.  

10.  Better neuroscience training for psychiatrists and psychiatric trainees.  We are past the point where a focus on pharmacology can inform a psychiatrist about how a prescription might affect brain functioning.  A detailed knowledge of signaling systems including many systems outside of the nervous system and how they affect plasticity is a requirement for the future.  A detailed knowledge of these systems is necessary to understand brain functioning and normal and abnormal conscious states.    There needs to be an emphasis on teaching neuroscience in psychiatric departments and correlating neuroscience with currently observed clinical phenomenon at a practical and theoretical level.

11.  Medical detoxification from substances needs to be widely available.  A lot of people forget that substance use disorders are in the DSM and there is a psychiatric subspecialty in Addiction.  Even though we have more addiction specialists than ever, the quality of acute detoxification is worse than ever largely because it is another rationed service.  People with significant withdrawal states are often sent home with a bottle of benzodiazepines or sent to a "social" detox setting with no medical supervision.  There are specific goals for detoxification from addictive drugs including the prevention of withdrawal seizures, the prevention of delirious states, the prevention of psychotic states, and the prevention of suicide during acute withdrawal.  It is a common expectation of the current system to expect a patient or their family to be managing withdrawal at home.   The secondary expectation of detox is to assist the patient with transitioning to a safe setting where they can stop using the drug they were just detoxified from.  My estimate from talking with primary care physicians is that only about 20% of the emergency departments and primary care physicians in any locale can refer people to functional detox units.  The non-medical powers that be in the health care system decided long ago that detox was  an "outpatient procedure."  In most cases the translates to sending a person home and hoping they will make it to an outpatient appointment or an AA meeting.

12.  The gross mismanagement of physicians has been a pathway to physician burnout, mass dissatisfaction, and a dumbed down assembly line approach to the practice of medicine and psychiatry.  Physicians don’t need to be told how many people to see in a day, what to document, or how to treat people.  The current collaborative care approach can be seen as being due (in part) to a mind numbing productivity approach that was invented by the federal government and the business world in the first place.   When I was trained as a physician, our teams knew what the resources were, knew what our tasks for the day were, and we could make a local resource allocation on that basis.  It was an extremely efficient way to practice medicine.  At some point, administrators developed “productivity” standards where physicians were expected to apply a totally subjective billing and coding scheme to a patient interaction and do that repetitively all day long.  There were rarely two interactions that were alike, but for the past 20 years physicians have pretended that they were and that this productivity concept had some real meaning.   Administrators could simply increase “productivity standards” to make it seem like more and more work was being done.  In some clinics this process reached an absurd level – 40 or 50 patients a day.  People with complex problems were being seen for minutes and physicians were going along with it because their salary depended on it.   Productivity is another managed care concept that needs to go. 

That is my top twelve list for fixing the broken mental health system.  They are obvious problems supported by my clinical experience.  They are consistent with the frequent problems I have had advocating for the resources I needed to treat patients with severe mental illness.  The government and business partnerships in health care have been obstacles to care.  As long as these partners continue to ration health care and siphon off large profits while rationing care and resources to the patients who are paying for them nothing will change.  This pattern has been most noticeable in psychiatric services.  Contrary to a lot of rhetoric, the problem with the mental health system is not the pharmaceutical companies behaving like other businesses.  It is not the DSM.  It can't be organized psychiatry because organized psychiatry is politically weak and ineffective.  It is not physician conflicts of interest because they are plentiful and the more important ones on the business side are never discussed.

This so-called system was brought to you by the government and the health care companies that lobby all politicians.  The idea that a system of medical care run by business people and politicians who know nothing about medicine or psychiatry is somehow a good idea, is an ongoing American pipe dream.

It is time for the country to snap out of it.


George Dawson, MD, DFAPA

Supplementary 1:  The photo credits here go to Ruzica Vuskovic, MD.

Supplementary 2:  I will be adding in links to previous posts at some point but ran out of time tonight.

Supplementary 3:  I added on Monday 11/17/2014.

Scourge Of Prior Authorization Finally Acknowledged?

A copy of Minnesota Medicine, the journal of the Minnesota Medical Association (MMA) was delivered to my office this morning.  I stopped paying dues to the MMA about 20 years ago.  My rationale was that I was already paying significant dues to two professional organizations that were doing nothing to protect me from the repeated abuses of the managed care industry - why pay a third to do an equally poor job?  I was probably more steamed at the MMA at the time because I realized that managed care in Minnesota was more than just an annoying business practice, it was institutionalized in both the statutes and administrative practices of the state government.   I sent the President of the MMA a letter to that effect.  I don't have his response but it did not persuade me to send them another check.  I can only guess that this is a marketing idea to persuade the disaffected that the MMA is now a vital organization that appreciates medical practice in the state in many cases has come perilously close to being a living hell.  That living hell is courtesy of managed care and the various heads of that hydra.

Despite those reservations, on the front page just below the journal title was this headline:  The Prior Authorization Burden and just below that the subtitle: The process is frustrating, time-consuming and costly.  No kidding.  Any casual reader of this blog may recognize that this is probably one of the only sites where you can count on rigorous criticism and aggressive opposition to all managed care techniques.  At the top of that list is prior authorization.  I have gone as far as coming up with a "no-Rx" logo that I use to symbolize the problem.  That symbol is at the top of this post. It means that a managed care company (MCO) or pharmaceutical benefit manager (PBM) can deny prescriptions and therefore medication to the patient.  That denial is also a denial of the prescription of the physician and everything that involves.  State and federal governments have granted these organizations this power based on some loose idea that it would save patients and the governments money.  These governments are still enamored with that idea despite the overwhelming evidence that money is not really saved, it is merely redirected to the bottom line of MCOs and PBMs.  The only people who pay the price are patients and physicians.

So my first and primary question was "Does the medical society finally get it?"  They certainly missed the boat on utilization review and as a result managed care organizations in Minnesota generally make the discharge decisions on patients.  Will they also continue to make decisions about what medications can be prescribed based on their profit margins rather than what a physician in a treatment relationship with the patient decides?  The initial example seemed hopeful.  It was the story about a primary care physician trying to prescribe a rescue inhaler for his asthmatic patient.  He had taken a specific brand of generic albuterol for years.  The prescription was rejected.  He wrote subsequent decisions for identical medications in the same category Proventil and that was rejected.  He sent in a script for ProAir and that was rejected.  He was told to choose another inhaler but not given a name to choose.  He picked Xopenex or levalbuterol rather than albuterol and that was accepted.  What is the rationale for a PBM having a doctor guess about which inhaler will be approved for days while a patient with severe asthma goes through the weekend without a rescue inhaler? In a word money, the only rationale for picking a newer and (usually) more expensive inhaler is that the PBM has some kind of financial deal with that manufacturer.

 The article does go on to explore that theme and references a study of six Minnesota Health Plans.  The researcher Barbara Daiker, RN, PhD found that there were 1,036 drugs that required prior authorization but only 6 were on the prior authorization list of all 6 health plans.  Only 26 more were on 5 of the 6 lists.  This level of variability suggests that the decisions are not based on scientific evidence or quality concerns but financial models.  It would have been very useful to know if any of these lists included generic drugs. Without a scientific or quality basis for these lists, the obvious model is a purely financial one.  That is also consistent with the tactics used by these companies that I have documented in this blog such as refusing to cover generic antidepressants that can be purchased for as little as $4.00 per month.

One of the facts about prior authorization is that  like most managed care tactics, the burden has fallen disproportionately on  psychiatric practice and patients with mental illness.  One of the first articles demonstrating the adverse effects of prior authorization was published in the New England Journal of Medicine in 1994 (2) showing that when prescription limits were imposed on patients with severe chronic mental illness it resulted in increased health care costs that exceeded the savings in medication by a factor of 17.  In a more recent study, Driscoll and Fleeter (3), estimated the adverse effects (hospitalization, lost wages, homelessness, incarceration, higher medical costs) of prior authorization applied to the population of Ohio residents with schizophrenia and bipolar disorder.  They used conservative estimates of the population at risk and treatment discontinuity as a result of prior authorization programs.  They determined associated indirect costs with these treatment discontinuities and summarized his results in the following table.

The Driscoll and Fleeter study replicates several other studies that illustrate the problems with the "cost savings" of prior authorization.  Those savings to an MCO or PBM are shifted to the patient and the taxpayer.  These studies are consistent with the recent concern about the mass incarceration of the mentally ill.  Nobody is paying attention to the fact that when this happens the cost of care is now paid by the correctional system and not the person's insurance.  If a person with a substance use problem is incarcerated any medication they take to maintain abstinence is generally discontinued resulting in more savings to the MCO.  In addition to the financial analysis, the psychiatric care of these persons is often severely disrupted because correctional systems are now imposing their own form of a limited formulary so that the patient may get a medication, but not one that has been carefully assessed to work.

These studies all demonstrate that "savings" from prior authorization is savings to a health care company and it does not benefit the patient involved.  The costs to the providers in the case of the above table were not even used but per my previous reference are considerable.  I would also add that since this study came out most of the original second generation antipsychotics are now generic drugs and that reduces the Annual Cost Savings considerably.  The estimates for Annual Additional Cost are much higher and don't include the paperwork costs for physicians.  In other words the net added cost of prior authorization for psychiatry is considerable higher in 2014 than it was in 2008.

With all of these considerations it is good to see the state medical society finally paying attention.  That doesn't mean anything will be done and the evidence for that is contained in this quote from Janet Silversmith, Policy Director of the MMA: "We are not trying to eliminate drug prior authorization.  We are just trying to add some sanity to the process.  As it's practiced now we believe drug prior authorization is an onerous, inefficient process that sometimes harms patients."

Why wouldn't any medical society want to kill that kind of process?


George Dawson, MD, DFAPA

Refs:

1:  Howard Bell.  The prior authorization burden.  Minnesota Medicine. November/December 2014:  18-25.  PDF

2:  Soumerai SB, McLaughlin TJ, Ross-Degnan D, Casteris CS, Bollini P. Effects of a limit on Medicaid drug-reimbursement benefits on the use of psychotropic agents and acute mental health services by patients with schizophrenia. N Engl J Med. 1994 Sep 8;331(10):650-5. PubMed PMID: 8052275.

3:  Howard Fleeter, PhD.  Estimate of the Net Cost of A Prior Authorization Requirement for Certain Mental Health Medications.  Prepared by Driscoll and Fleeter for National Alliance on Mental Illness Ohio.  August 2008. (Table used with permission).



Supplementary 1:  The "No - Rx" logo simultaneously symbolizes no prescription for the patient, no acceptance of a prescription from a trained and licensed physician, cost savings for the insurance entity that contracts with the patient to cover their prescription medications, and increased costs for all of the providers, employers, governments and correctional systems that need to address discontinuities in care.

Clozapine As A Fictional Murder Weapon On The Walking Dead

clozapine (Clozaril)

clonazepam (Klonopin)

When something doesn't fit my typical hypothesis testing interview style, I start to think that there are other things going on.  Things that might not be obvious and things that I will need to piece together with further evidence gathering and collateral information.  That is what happened when I was watching television last weekend.  It happens all of the time in real life.  I remember the day when I was a second year resident and my attending asked my: "Suppose that you are at a party and this person comes up to you and starts to act in a certain way.  Do you tell yourself: "I am off the clock" and try to react in a way other than a psychiatrist might act or do your think about that interaction like a psychiatrist would?"  There was some uncertainty there as a rookie, but not after 3 decades of practice.   You see the world as a psychiatrist.  That is why I suddenly became much more attentive when I heard the words clozapine and clonazepam mentioned in a very popular television drama last weekend.

Before any further consideration, this is about the implications of a purely fictional scenario.  This post is more about the motivations of the author or authors than psychiatric treatment.  At that level it is probably more about individual or cultural perceptions than reality.  I was watching the highly popular television series the The Walking Dead  last weekend.  This series is all about surviving a zombie apocalypse.  In this scene, a group of survivors is providing some kind of emergency medical care.  They are in a large hospital building.  I was surprised when the ragged physician gave the order to give a patient "75 mg of IM clozapine".  Any psychiatrist or psychiatric nurse knows that there is no IM form of clozapine and that according to the standard titration that dose is probably too high in any clozapine naive patient on day 1.  Apparently the writers of the show knew at least some of that because the actress who was working on the doctors orders had to take clozapine tablets out of a standard large pharmacy bottle and grind them up with a mortar and pestle so that they could be dissolved and injected.  She proceeded to inject the fictional patient with clozapine.  In a few minutes, the treated patient developed tonic-clonic seizures and dies.  She goes back to confront the original physician who gave her the order and is told: "No I said clonazepam and not clozapine."  Interestingly this combination is not on the list of look-alike, sound-alike or confused drug names by ISMP , but it is in this document about using TALL MAN font conventions to prevent mistakes among drugs that look alike.  On page three we learn that clonazePAM- cloZAPine-KlonoPIN are confused medications.  I think that anyone without experience in these medications might make that mistake.  Of course for the purpose of drama, we learn later that the physician giving the order actually knew that the deceased man was a physician.  They previously worked together in a hospital setting.  In the dog-eat-dog world of the zombie apocalypse, the ordering physician did not want any competition for his medical position.  He did not want to risk elimination by his more ruthless leader.  He intentionally ordered his assistant to give a clozapine injection and then lied and told her that he said clonazepam and not clozapine.

I posted the structures here to illustrate that before there were administrators focused on the confusion between names there were chemists to show that each of these compounds is unique.   Studying pharmacology and those technical details adds another layer of appreciation.  Psychiatry adds another layer of meaning on top of that.  I have seen the benzodiazepine trends and concluded like many psychiatrists after years of practice that clonazepam and other benzodiazepines might be useful for the first months of treating anxiety or panic.  As an add-on for anxiety in people with severe problems they don't add much.  In the end there are still the same problems and an additional addictive medication.  When I think about clonazepam, I am also reminded that even the professionals can be confused.  I used to work at a place where it was not considered a benzodiazepine and not subject to the same security precautions - even after I pointed that out.  Clozapine on the other hand can be a life changing medication.  People with refractory psychosis and mood symptoms become clear and function at a much better level.   If clozapine did not have significant limitations from toxicity, I doubt than there would be a need for any other antipsychotic.  It is the only one with clear advantages in terms of symptoms relief, improved function, protection against suicide, and it even treats tardive dyskinesia and other movement disorders.  But the way it stands there are significant side effect limitations and  it is the antipsychotic that psychiatrists worry about the most.  

We have a case of homicide by injection of 75 mg clozapine.  Does that hang together as being plausible?  It also triggers an entire series of question about: "Why clozapine?"  Clozapine is a fairly esoteric second generation antipsychotic.  It is indicated for treatment refractory schizophrenia and a lot of experts believe it is underutilized because of its superior efficacy in this population.  It also is the only medication that has been shown to have anti-suicide properties in a double-blind clinical trial.  Those superior effects occur in the context of a wide range of toxicities that require close monitoring including weekly to monthly complete blood counts with differentials (depending on the time course of treatment)  for the length of treatment with the drug.  In addition to hematological side effects the drug can cause seizures and a number of other organ specific toxicities like myocarditis.  It should only be prescribed by experts familiar with its use and registered to prescribe it and follow the white blood cell counts.  If the white blood cell counts fall below a certain parameter, the clozapine must be discontinued and not restarted.  Clozapine can cause fatal agranulocytosis.  I view clozapine as one of the most beneficial drugs in psychiatry and one of the most toxic.  Clonazepam on the other hand is a benzodiazepine.  It can be used to treat anxiety and panic attacks.  It can also be used to treat seizures, but I have rarely seen it used for that purpose.  The main toxicity is excessive sedation and the main clinical problem is that it can be addicting.  But in terms of toxicity, it is generally well tolerated.

My first question is why clozapine would be available in the post apocalyptic pharmacy?   In any shorter term situation the medications that run out first are maintenance medications for chronic conditions.  In this case, the survivors are supposed to be in Grady Memorial Hospital, one of the largest hospitals in Atlanta.  I suppose it is possible that they would have a larger supply of clozapine since they are a metro hospital and if psychiatric services were as bad before the apocalypse as they currently are they would typically have a significant number of people in the emergency department that may be taking clozapine.  The second question is - can it be given intramuscularly?  It turns out it can be.  A 1999 reference from Lokshin, et al describes their use of parenteral clozapine in 59 patients.  They are using the drug for acute stabilization of inpatients and they do not describe whether or not their patients are taking other medications or are medication naive.  They do not specify dosing but in one case described the problems with giving large intramuscular injections of up to 300 mg in injectable clozapine when  patient refused the same oral dose.  They had surprisingly few side effects, no fatalities, and no seizures.   Unless I missed a reference somewhere this may suggest that the author of The Walking Dead episode believed that clozapine is a lot more toxic (and lethal) than it really is.   Or do they have access to other information?  That also brings up the question, if you were a physician with access to the post-apocalyptic pharmacy would there be more toxic and more lethal medication that could be used for that purpose.  Most probably, but I will not be speculating about that here.

There are a large number of questions that come up if you think about the possible intentions or biases here that involve the use of clozapine in a fictional plot.  In situations like this, I prefer to contact the author directly and ask them what they were thinking.  After a significant amount of time searching, I learned that there may have been some controversy with the writers of this series, but I could not find a single e-mail or snail mail address where I could send them that question.  I would certainly prefer to get an answer from the author or authors.  How did they first hear about clozapine?  Why did they decide to use it in this case?  Do they have a medical advisor who suggested it?  Do they have a personal relationship with anyone who takes clozapine?  Do they have an opinion about the medical treatment of psychiatric disorders in general?  There is really a long list of questions.

And finally there are also the practical treatment implications.  Up to 17.3 million people watch The Walking Dead, a large percentage of them 18-49 year olds.  I am sure that  has implications for informed consent conversations between psychiatrists and patients and their families.  We live in a country where 21% of 18-29 year olds get their news about Presidential campaigns from The Daily Show.  After hearing the name from a psychiatrist somebody is bound to say:  "Wasn't that the medication that we heard about on The Walking Dead?"  The standard reply is that medical conventions and treatments are not immune to artistic interpretation and all areas of medicine are similarly affected.

I may be missing something but it just seems like an unusual choice for this medication in this plot to me.


George Dawson, MD, DFAPA



Ref:

1: Lokshin P, Lerner V, Miodownik C, Dobrusin M, Belmaker RH. Parenteral clozapine: five years of experience. J Clin Psychopharmacol. 1999 Oct;19(5):479-80. PubMed PMID: 10505595.