Pharmacosurveillance, Suicide and Antidepressants

I was board certified in geriatric psychiatry initially in 1991 and have been a member of the American Association of Geriatric Psychiatry since then.  Members receive the American Journal of Geriatric Psychiatry.  Treating depression in geriatric patients is a a very rewarding experience for psychiatrists because depression often masquerades as a severe medical problem like dementia, chronic pain, or Parkinson's disease.  Treating the underlying depression clears the manifestations that appear to be these other illnesses.  Even pure depression in an elderly patient can lead to significant medical compromise because of diminished physiological reserve and rapid compromise of nutrition or mobility as the result of sleep deprivation and inadequate intake.  That can occur as the result of discontinuing long standing antidepressant maintenance therapy.  The elderly also have some of the highest rates of completed suicide and that also factors in decisions about maintenance antidepressant treatment as well as effective psychosocial interventions to address that problem. 

In the January edition of the AJGP, Erlangsen and Conwell look at the relationship of completed suicide and antidepressant redemption in a nationwide cohort in Denmark.  The methodology of this study is not available in the United States.  Denmark has several registers based on a unique personal identifier for all of its citizens.  The authors looked at the Register of Medicinal Product Statistics and suicide as a cause of death in the Registry of Causes of Death for a cohort of people who were 50 years of age or older on January 1, 1996 through December 31, 2006.  Data on antidepressant use was identified and classified into tricyclic antidepressants, selective serotonin reuptake inhibitors and other types of antidepressants.  A treatment episode was considered to have occurred if a second prescription of antidepressants was filled and the patient appeared to be taking 0.75 tablets per day.

In terms of sheer number the study included 1,222,941 men and 1,346,973 women.  In the follow up period deaths by suicide numbered 3,061 men and 1,456 women.  As illustrated by Figure 1. below there is a decreasing number of those dying by suicide who redeemed antidepressant prescriptions.  In the 80+ year olds it was less than one in four women and less than one in eight men.  Trends were noted that percentage of men and women dying of suicide who took antidepressants decreased with increasing age.  This data is consistent with previous data that show that most elderly patient die by suicide are not in treatment at the time and they have clinically significant symptoms of depression.         

 (graphic removed by copyright manager - please see the original article)

This study is a good example of what kind of data is available with large databases across entire populations.  The limitations of the data are discussed by the authors including the fact that the pharmaceutical registry does not have any diagnoses and antidepressants have numerous indications.  They discuss why antidepressant redemption may not be the optimal proxy for antidepressant use.  In this case their study design considering only people who have redeemed the second antidepressant prescription to be in treatment.  That contrasts with some data suggesting the highest risk for suicide may occur in the initial days or weeks of antidepressant treatment.  They point out the usual qualification about association versus causality, but also conclude that "it is possible that antidepressants protect the oldest old from death by suicide" and point out the important public policy question of how to identify these patents.

There is a similar interesting study available that looks at a database that includes 3/4 of the population of the Netherlands (see reference 2).  It looks at the correlation between antidepressant use and both suicide and violence and concludes that there are significant negative correlations with both.  In other words increased antidepressant use led to decreased rates of suicide and violent behavior over the years 1994-2008.

When I read this study, I was also interested in what medical specialty is prescribing the bulk of the antidepressants.  I e-mailed one of the authors and asked that question.  The response was that the specific specialty of the prescriber was unknown but that bulk of antidepressants in Denmark were prescribed by primary care physicians and the likelihood of antidepressant prescription by primary care increases with patient age.  Psychiatric consultation was more likely to occur at a younger patient age.

In the United States we need pharmaceutical registries similar to the Danish registry.  We need a more factual basis to evaluate issues of pharmaceutical use over time, complications of prescription drugs, over prescription of drugs, and adequate drug utilization.  For example, with the recent concerns about stroke risk factor reduction in the elderly and stroke risk reduction from atrial fibrillation graphs similar to Figure 1. looking at all of the relevant medications may prove very useful.  Practically all pharmacy data in this country is proprietary and the largest database was developed to see if pharmaceutical representatives were having an impact on prescriptions written by individual physicians.  The  current development by individual states focused on the prescription of controlled substances is an opportunity to expand that data to identify important public health trends and reduce speculation.
  

George Dawson, MD, DFAPA

Figure 1. is reprinted from Am J Geriatr Psychiatry 2014 Jan; 22(1) Erlangsen A, Conwell Y. Age-related response to redeemed antidepressants measured by completed suicide in older adults: a nationwide cohort study, with permission from Elsevier. 

1:  Erlangsen A, Conwell Y. Age-related response to redeemed antidepressants measured by completed suicide in older adults: a nationwide cohort study. Am J Geriatr Psychiatry. 2014 Jan;22(1):25-33. doi: 10.1016/j.jagp.2012.08.008. PubMed Central PMCID: PMC3844115

2:  Bouvy PF, Liem M. Antidepressants and lethal violence in the Netherlands 1994-2008. Psychopharmacology (Berl). 2012 Aug;222(3):499-506. doi: 10.1007/s00213-012-2668-2. Epub 2012 Mar 7. PubMed PMID: 22395429; PubMed Central PMCID: PMC3395354

Can You Trust Your Physician?

I could not help but respond to the Psychiatric Times article with the same title that they e-mailed me this morning.  Trust in an interesting concept when you live in a country that is politically managed for laissez faire capitalism and the only protection that the average citizen has against various cartels is caveat emptor.  The vocal irrational biases against psychiatry should discourage blind trust of psychiatrists even further.  Early in my career, I stayed away from any interpretive approaches to a lack of trust and took a simple cognitive behavioral therapy (CBT) approach.  That goes something like this: "I don't think there is any basis for you to trust me or not trust me.  I would encourage skepticism and taking a look at what I actually do for you.  If you find the recommendations, discussions and treatments that I recommend are useful, that is more clearcut evidence that I might be helpful to you.  If not, certainly let me know and we will figure out what to do  about it".  Many of the people I have worked with over the years who had "trust issues" have found that to be a useful approach.

In reading the article, I find out that it is about the legal requirements involved in informing women about abortion. specifically the fact that in some states physicians are now required to tell women that a fetus will feel pain as it is aborted.  Additional states require women to pay for an ultrasound evaluation and view the fetal image before the abortion, advise women that abortion leads to an increase in breast cancer, and refer women for counseling after advising them that an abortion places them at risk for adverse mental health consequences.  The authors cite the scientific evidence to the contrary in all cases.  Can you trust a physician who is reciting abortion law boilerplate when they are advising you about that procedure?  Probably as much as you can trust a physician doing a safety assessment in a situation where they are prohibited by state law from discussing firearms that the patient may have at home.

 I don't think anyone should be surprised about the lack of science involved when politicians decide to manipulate physicians to do their bidding.  I currently live in one of the most liberal states in the United States and every year I get a letter informing me of the number of abortions performed every year and reminding me of my obligation to report if I perform an abortion.  It is a state law that all physicians receive this letter, even if they are psychiatrists who don't do any surgical procedures.  The intent of the letter is to clearly intimidate physicians into not performing abortions.

To quote the downside from the authors:  "These politically motivated laws undermine the concept that medical decision-making is based on scientific evidence. They force physicians to act as agents of the state government rather than put their patients’ interests first. They are intended to intimidate women so that they will not have abortions. They are corrosive to honesty in the physician-patient relationship, interfere with the physician’s responsibility to the patient, and violate medical ethical principles."

I think that any reasonable physician would agree.  I have been pointing out for decades that physicians have been agents of the state for a long time.  Colluding with managed care and all of its governmental variations is a clear example.  The entire managed care manual on when to discharge people from hospitals and how to do that has nothing to do with science.  The entire concept that all medications in the same drug class are equivalent has nothing to do with science.  Practically all of the rationing that occurs by the government and managed care companies has nothing to do with science.  But it doesn't stop there.  All state statutes having to do with the duty to warn have nothing to do with science and more to do with where the deep pockets are located.  In the original case precedent the perpetrator was detained and interviewed by the police and released before the homicide.  It was a clear example of the failure of the police to protect the victim and yet that was spun into the responsibility of clinicians to warn potential victims.  How much legislation is out there to create work for trial attorneys?

I was at a conference a few years ago where hospice care was being discussed as the latest innovation in hospital care.  When I thought about how people are assessed and discharged from acute care hospitals my question seemed obvious:  "Since there are care managers forcing discharges, isn't there a potential conflict of interest if hospice care is seen as the fastest way to discharge somebody from a hospital?"  The result was dead silence, a moment of confusion ("He really didn't ask that question did he?"), and then I was ultimately ignored as the speaker moved on.  With all of the focus on what are really trivial conflicts of interest in psychiatry, think about that for a moment.  A care manager representing the business interests of the hospital, the MCO/ACO, and the political interests of the politicians interfering with the practice of medicine has options available to them with the potential to short circuit care and provide less intensive care than might be recommended by a physician.

I was in a clinic recently where I was given an impressively long list of exceptions to patient privacy.  I picked up one of my electrical engineering journals the other day and was warned about how the Internet of Things (IOT) will be collecting all sorts of data on the average citizen, but that the owners of the data (Google, Facebook, etc), hope that the average citizen will see the worth in all of this information being in their hands.

Turning over all of this information and power over to the political and business classes is an obvious mistake.  Eliminating what has been described as a mandarin class - the physicians is another.  Unfortunately physicians and their professional organizations are completely inept at dealing with this problem and we are left with these inappropriate political intrusions and physicians acting like agents of the state and business cartels.

That means that politicians will not only try to manipulate who is born based on their ideology, but more importantly who has access to medical care and the level of intensity and who dies.  It is happening right now and it should be a lot scarier than a fictional robot time-traveling back from the future.

Remember the CBT approach to your physician, your health plan and your insurance company and make sure they are doing what you want them to do and not what some politician or business manager wants them to do.

George Dawson, MD, DFAPA

Cognitive Enhancement IS Cheating

One of my colleagues posted a recent commentary from Nature on how the idea of the smart pill has been oversold.  The basic theme of the commentary is that there is no good evidence that treatment of ADHD with stimulants improves academic outcomes.  The author reviews a few long term studies and contends that differences between the medication and placebo seem to wash out over time and therefore there is no detectable difference.  Her overall conclusions seem inconsistent with her view that:  "For most people with ADHD, these medications — typically formulations of methylphenidate or amphetamine — quickly calm them down and increase their ability to concentrate. Although these behavioural changes make the drugs useful, a growing body of evidence suggests that the benefits mainly stop there..."

A question for any cognitive psychologists out there - is it possible to improve your concentration and have that not improve learning?  I can't imagine how that happens.  If you go from not being able to read 2 pages at a time to suddenly reading chapters at a time, how is that not enhanced cognitive performance?  If you go from staring out the window all day and daydreaming to being able to focus on what the teacher is saying how will that not lead to an improved outcome?  The idea that improved attention - a central factor in human cognition will not affect anything over time suggests to me that the measures being used for follow up are not very robust or that this is a skewed sample of opinion.   

For the purpose of cognitive enhancement, the typical users are students trying to gain an edge by increasing their study time.  Anyone who has experienced college and professional school realizes that here is a large amount of information to be mastered and it is not presented in an efficient way.  I can never recall a professor who advised us of the important guideposts along the way or gave us any shortcuts.  The usual message is study all of this material in depth every day or you will fall behind.  That approach in general is consistent with gaps in the ability to study either through the normal course of life or the competition for intellectual resources by 3 or 4 other professors who regard their courses as important.  That typically results in a pattern of cramming for specific key exams.  Although I have not seen any specific studies, stimulant medications are generally used for this purpose and in many cases the use is widespread.  There is a literature on the number of college students who may be feigning ADHD symptoms in order to get a prescription and that number could be as high as 50% (4,5). 

What  about the issue of stimulants acting as a smart pill in people who don't have ADHD?  In the most comprehensive review I could find on the subject (6) the authors review laboratory studies and conclude that in those settings stimulants enhance consolidation of declarative learning to varying degrees, had mixed effects on working memory, and mixed effects on cognitive control.  On 8 additional tests of executive function, the authors found that stimulant medication enhance performance on two of those tests - non-verbal fluency and non-verbal intelligence.  They have the interesting observation that small effects could be important in a competitive environment.  Their review also provides an excellent overview of the epidemiology of stimulant use on campuses that suggests that the overall prevalence is high and the pattern of use is consistent with cramming for exams.  They cite a reference that I could not find (7) that was a reanalysis of NSDUH data suggesting that as many as 1 in 20 stimulant users may have a problem with excessive use and dependence.     

Getting back to the theme of the Nature commentary, it is ironic that the smart pill theme is being called into question when it was the subject of a Nature article years earlier advocating for the use of cognitive enhancement.  In that article Greely, et al come to the somewhat astounding conclusion: 

"Based on our consideration, we call for a presumption that mentally competent adults should be able to engage in cognitive enhancement using drugs."

They arrive at that conclusion by rejecting three arguments against this practice.  Those arguments include that it is cheating, it is not natural and it is drug abuse.  Their rejection of the cheating argument is interesting because they accept the idea that performance enhancing drugs (PEDS) in sports is cheating.  They reject that in cognitive enhancement claiming that there would need to be a set of rules outlining what forms of enhancement would be outlawed and what would not (e.g. drugs versus tutors).  To me that seems like a stretch.  I think that sports bodies select performance enhancing drugs as a specific target because it clearly alters body physiology in a way that cannot be altered by any other means.  There is also plenty of evidence that the types of PEDS are dangerous to the health of athletes and associated with deaths.  Their conclusion about drug abuse: "But drugs are regulated on a scale that subjectively judges the potential for harm from the very dangerous (heroin) to the relatively harmless (caffeine).  Given such regulation the mere fact that cognitive enhancers are drugs is no reason to outlaw them."   That is a serious misread of the potential addictive properties of stimulants and the previous epidemics that occurred when the drugs were FDA  approved for weight loss, the epidemic of street use in the 1970s and the current and ongoing epidemic of meth labs and methamphetamine use throughout much of the USA.

These authors go on to outline four policy mechanisms that they believe would "support fairness, protect individuals from coercion, and minimize enhancement related socioeconomic disparities."  At first glance these lofty goals might seem reasonable if society had not already had in depth experience with the drugs in question.  The clearest example was the FDA approved indication of amphetamines for weight loss.  What could be a more equitable application than providing amphetamines to any American who wanted to use them for weight loss?  The resulting epidemic and reversal of the FDA decision is history.  A similarly equitable decision to liberalize opioids in the treatment of chronic pain had resulted in another epidemic of higher lethality due to differences in the toxicology of opioids and amphetamines. 

The contrast between these two commentaries in Nature also highlight a couple of the issues about the way medical problems and treatment is portrayed in the media.  This first is that you can't have it both ways.  Quoting a researcher or two out of context does not constitute an accurate assessment of the science involved.   Some of the authors in the first commentary are highly respected researchers in cognitive science and they clearly believe that cognitive enhancement occurs and it should be widely applied.  Nature or any other journal cannot have it both ways.  A more realistic appraisal of the problem is addressed in reference 6.   The second issue is that in both cases the authors seem blind to the addictive properties of stimulants and they are ignorant of what happens when there is more access as exemplified by the FDA misstep of approving stimulants for weight loss.  Do we really need a new epidemic to demonstrate this phenomenon again?  Thirdly, all of this comes paying lip service to non - medication strategies for cognitive enhancement.  We can talk about the importance of adequate sleep - a known cause of ADHD like symptoms and if we are running universities and workplaces in a manner that creates sleep deprived states, the next step is reaching for pills to balance an unbalanced lifestyle.  The new rules for residency training are a better step in the right direction.  Fourth, college is a peak time for alcohol and substance use in the lives of most Americans.  These substances in general can lead to a syndrome that looks like ADHD.  It is highly problematic to make that diagnosis and provide a medication that can be used in an addictive manner.  It is also highly problematic to think that treating an addicted person with a stimulant will cure them of the addiction and yet it happens all of the time.

There is plenty of evidence to suggest that cognitive enhancement is cheating.   Much of my career has been spent correcting the American tendency of trying to balance one medication against another and using medications to tolerate a toxic lifestyle or workplace.  It does not work and the current group of medications that are being put forward as cognitive enhancers are generally old drugs with bad side effect profiles particularly with respect to the potential for addiction.

If you want safe cognitive enhancers that can be made widely available, they have not been invented yet.  

George Dawson, MD, DFAPA




References:

1: Sharpe K. Medication: the smart-pill oversell. Nature. 2014 Feb 13;506(7487):146-8. doi: 10.1038/506146a. PubMed PMID: 24522583.

2: Greely H, Sahakian B, Harris J, Kessler RC, Gazzaniga M, Campbell P, Farah MJ.

Towards responsible use of cognitive-enhancing drugs by the healthy. Nature. 2008 Dec 11;456(7223):702-5. doi: 10.1038/456702a. Erratum in: Nature. 2008 Dec 18;456(7224):872. PubMed PMID: 19060880.

3: Feldman HM, Reiff MI. Clinical practice. Attention deficit-hyperactivity disorder in children and adolescents. N Engl J Med. 2014 Feb 27;370(9):838-46. doi: 10.1056/NEJMcp1307215. PubMed PMID: 24571756.  

4: Green P, Lees-Haley PR, Allen LM., III The word memory test and the validity of neuropsychological test scores. J Forensic Neuropsychol. 2002;2:97–124. doi: 10.1300/J151v02n03_05

5: Suhr J, Hammers D, Dobbins-Buckland K, Zimak E, Hughes C.  The relationship of malingering test failure to self-reported symptoms and neuropsychological findings in adults referred for ADHD evaluation.  Arch Clin Neuropsychol. 2008 Sep; 23(5):521-30.

6: Smith ME, Farah MJ. Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals. Psychol Bull. 2011 Sep;137(5):717-41. doi: 10.1037/a0023825. Review. PubMed PMID: 21859174 

7: Kroutil LA, Van Brunt DL, Herman-Stahl MA, Heller DC, Bray BM, Penne MA. Nonmedical use of prescription stimulants in the United States. Drug and Alcohol Dependence. 2006; 84:135–143.10.1016/j.drugalcdep.2005.12.011 [PubMed: 16480836]

The Medicaid Emergency Department Study

There is an important study on the emergency department (ED) and health care policy in the January 17 edition of the journal Science. It looks at the question of whether not health insurance increases or decreases ED use.  This has been a political football for years.  The debate has been that increased insurance enrollment would prevent excessive ED utilization but the evidence has been sparse.  Some surveys have shown that the uninsured view the high cost of ED services and the financial repercussions are a deterrent.  On the increased utilization side is the economic argument that prepaid services lower the cost and therefore increase the use of all medical services across the board.  Another variable is the overall economy.  In an economic downturn, people use less goods and services including medical services.

Mapped onto the ED utilization problem is the EMTLA law or The Emergency Medical Treatment and Labor Act.  This law states that no person requiring medical stabilization can be turned away from an ED based on ability to pay.  A variety of mechanisms shifts the cost of care to the facility and physicians providing the care.  In the case of psychiatric services, EDs are obligated to find an open bed to transfer the patient.  In most states the majority of hospitals with EDs do not have psychiatric units, and that can result in patients being held for long periods of time until a bed opens up or transfer to beds across the state.  More radical solutions to that problem have included discharging a person untreated back out to the street or discharging them after a certain time interval if a bed could not be identified.

The scope of the problem of psychiatric services in the ED has not been well studied.  Some of the large studies suffer from an inadequate look at diagnoses, crisis care, patient flow and disposition and outcomes.  Before this study, I could not find any studies with adequate detail about diagnoses.  The other consideration is selection bias.  In most metropolitan areas, emergency services brings patients with psychiatric crises to identified hospitals with the largest psychiatric services.  These services typically have large capacity and become catchment areas for large areas of the states they are located in.  They can also be overwhelmed due to various factors that affect patient flow.  Most of these factors are directly related to the closure and rationing of psychiatric services in acute care but also residential facilities, clinics and community support services for the severely disabled.

The design of this study is interesting because it is randomized based on a political initiative.  In 2008, Oregon started a limited expansion of Medicaid.  They drew 30,000 names from a pool of 90,000 people.  There were 8 drawings between March and September 2008.  Previous studies on outcomes by the same authors showed that Medicaid assignment led to reduce depression and improved general health but it did not impact several general measures of general health, employment, or earnings.  In this study they looked at 12 hospitals that are the catchment area for Portland and surrounding suburbs.  These hospitals have half of the annual admissions in the state.  The study ran for 18 months, and was an intent-to-treat analysis of the randomly selected Medicaid enrollees and the non-selected matched on demographic variables.

The primary result of the study showed that Medicaid enrollment was associated with a significant use in ED services.  The increase was 41% relative to the control group.  There was no difference in the number of visits resulting in admission but increases in most other types of visits, including those that would be treatable in an outpatient clinic.  For some reason these differences were detected in administrative but not self reported data.  The authors look at three potential reasons for those differences.  The discussion of study limitations focuses primarily on the fact that the low income population studied may differ significantly from other low income populations and limit its generalizability.  The author's also comment on how establishing primary care can logically increase the likelihood of ED utilization.  The commonest scenario there is a patient with with either risk factors or chronic illnesses that calls their primary care clinic and is advised to go to the ED because of the anticipated length or complexity of the required evaluation.   That factor could not be studied with the available data.  In the case of psychiatric services that is typically a change in mental status, suicide risk , aggressive behavior or need for intoxication or detoxification.

One of the features of this study of interest to psychiatrists is the supplementary data.  Table S10 lists "Select Conditions (control sample only)" for a total of 17,498 ED visits separated by category.  A total of 1346 or 8.4% of all visits were for "Substance abuse and mental health issues."  Of that sample, 3% were mood disorders, 2% alcohol related disorders, 1.5 % anxiety disorders, 0.9% schizophrenia and psychotic disorders, and 0.8% substance related disorders.  In looking at visits per condition increased ED utilization occurred for injuries, headaches, and chronic conditions but not mood disorders or substance use or mental health disorders.  It is not possible to see the distribution of ED visits by hospital and with what is known about these distributions on metro areas it is likely that a few of the 12 hospitals had most of these visits.

In the weeks to come, I anticipate that there will be an active debate on the economic and political implications of this study.  From a psychiatric perspective it does not really capture the scope of the problem of how we got to the current predicament of discharging people with psychiatric and substance use problems untreated from emergency departments.  Nobody seems to consider that the ED problem exists as a result of rationing at multiple levels and a physician productivity model that values a stereotypical low to moderate complexity visit.  Most clinics and even urgent care settings have limited flexibility to assess some of the suggested ED problems like new chest pain even though in this study 93.1% of the chest pain assessed was nonspecific and 3.5% represented an acute myocardial infarction.  A few conclusions that I come to:

1.  This study is well done, unique and seems to have a highly significant finding that increased insurance to a low income population leads to increased ED utilization rather than less.  Caution is needed in the interpretation of that data.  A major weakness of any study like this is the fact that it is all of the data is administrative rather than clinical.  This is a major weakness of practically every data set used to establish health care policy in the past starting with the RAND studies on overutilization of hospitalizations and procedures relative to what was determined by the PROs of the 1990s.  These studies showed that when the data was reviewed by non-biased reviewers with no conflict of interest, there was minimal to no overutilization.  It is probably time to consider that we need better data.

2.  All elements in the system are not equivalent - no 2 EDs are the same.  In any state you can walk into an ED attached to a Level 1 trauma center and burn unit or one that is staffed by moonlighting physicians or residents who may not be emergency medicine specialists.  That will naturally affect referral patterns and overcrowding phenomenon.  Detailed patient flow pattern in and out of the busiest EDs with enough granular data about that phenomena is probably more important in addressing the problem than a look at a single global insurance decision.  Data in this study and others suggests that the increased ED use is based on rational decision making about medical conditions and previous surveys on wanting to avert a financial catastrophe.

3.  Targeted interventions to reduce ED use is specific populations are highly effective.  Assertive Community Treatment (ACT) teams for people with chronic mental illness are a good example.  In these interventions teams have their own crisis programs independent of EDs as well as medical staff who are available to the patients 24/7.  Their goal is also to avoid psychiatric hospitalizations and they are very good at that.  As clinics are acquired and consolidated under various managed care organizations the likelihood of consulting with a person from your primary care clinic after hours decreases significantly and that probably means more contact with the ED.

4.  Urgent Care facilities are a logical extension of primary care clinics after hours and there is currently no psychiatric equivalent.  A clinic with adequate multidisciplinary mental health staff would seem like a better options than being seen in an ED.  There currently do not appear to be any facilities like this for mental health other than county government based crisis lines that vary considerably form county to county.

Despite all of the considerations I have listed above and more, I do not expect a more sophisticated look at this issue.  Our politicians are incapable of it and the conflicts of interest related to the business side of medicine will typically carry the day.  There will be some ideological arguments about economic theory but in the end, what is good for business will carry the day.

Increased utilization of the ED is looking better and better for business every day.    

 

George Dawson, MD, DFAPA



1: Taubman SL, Allen HL, Wright BJ, Baicker K, Finkelstein AN. Medicaid increases emergency-department use: evidence from Oregon's Health Insurance Experiment. Science. 2014 Jan 17;343(6168):263-8. doi: 10.1126/science.1246183. Epub 2014 Jan 2. PubMed PMID: 24385603.

2: Fisman R. Health care policy. Straining emergency rooms by expanding health insurance. Science. 2014 Jan 17;343(6168):252-3. doi: 10.1126/science.1249341.  Epub 2014 Jan 2. PubMed PMID: 24385605.

Doubling Down on The Miserable Patient

The need for managed care and the efficiency of the electronic health record are two of the biggest myths in the American health care system today.  Here is what really happens.....

I have had the occasion to be a miserable patient for the past 6 weeks.  That is what happens when you have asthma and nothing works or at least nothing seems to work very well.  Throughout the course of the illness I have dutifully kept my primary care physician up to date, but so far I have ended up seeing 6 different physicians over that time.  I received prescriptions for three different inhalers, a nebulizer machine, and two different varieties of nebulizers - albuterol and levalbuterol.  Hundreds of dollars of medications not covered by my health insurance that don't work or cause significant side effects.  The levalbuterol was prescribed because it was supposed to have fewer side effects and it worked out just the opposite and caused significant side effects with a heart rate up to 140 beats per minute.   I needed to take these treatments 3 times a day followed by another inhaler.  This is a story of what should be a very simple task of getting enough medicine to keep breathing and in this case it is the albuterol sulfate nebulizer solution.  For anyone not familiar with this product it comes in disposable 3 ml plastic vials.  You just crack it open and pour it into a nebulizer machine and inhale the solution until it is gone in about 5-10 minutes.

The nebulizer ampules come packaged inside a foil envelope inside a box.  The prescription on the other side of this box reads: "Nebulize 1 vial every 6 hours as needed for wheezing or shortness of breath."  Assuming that I continue to use them at a rate of 3 vials, that is about 90 per month.  About a week into it, I noticed I had just a couple of vials left and called the pharmacy to get more.  This is how it went (M=me, P=pharmacy, from memory and not a transcript):

M:  Yes - I am calling to refill a prescription for albuterol nebulizer solution (details given)
P:   Sorry but you have no refills on that prescription we will have to fax your doctor (reads MD name)
M:  That was the urgent care doctor, my doctor's name is Dr. Smith (details given)
P:   Well we will have to fax him then.
M:  I think you may have made a mistake on the original prescription since the paperwork I have from urgent care says that I should have gotten 75 vials and I only got 25 (see lower left corner of the label)
P:   No that is correct, we dispense them by volume rather than number.  The insurance company mandates that we do it that way - like cough syrup.
M:  That doesn't make any sense to me.  Each one of these vials is supposed to be a single dose and if I am taking three a day that is 90 vials per month.
P:   The only other way to get more vials is if your doctor writes "90 vials" on the prescription that he sends us.....
M:  He already wrote 75 and you gave me 25.
P:   No he has to write "75 vials" and spell out "vials".

At that point, I leave both a voicemail and an e-mail through the health plans messaging system for my personal physician to send in a new prescription for 75 vials of the solution.  The next day we are having one of the largest snow storms of the year and I am commuting 80 miles a day on glare ice and no visible road surface.  My commute time is 2 to 3 times normal.  I call ahead to make sure the prescription will be ready:

M:  I am calling about that albuterol nebulizer solution.
P:   We got the prescription from your doctor, but the insurance says they won't approve it because it is too early.
M:  What do you mean it's too early?  I am using it exactly as directed and you are only giving me 1 weeks worth of medication at a time.  How can it be too early?
P:   Well that's what they are saying....
M:  Look - I need this medicine to breathe.
P:   OK the medicine is approved.

I am questioning what is happening here.  I know she was not on line with the "insurance company".  Why did she suddenly change her mind on giving me a medication that I am essentially paying for out of pocket?  Do they have a secret directive that tells them to only give up the medicine if the patient appears to be in respiratory distress?  Why does the high deductible insurance have anything to say about this anyway?  They are policing my prescriptions for non-addicting medication and they have become an obstacle to my health care.   It made me think about all of the "Dear Dr." letters that are sent out by pharmaceutical benefit managers (PBMs) and managed care organizations (MCOs) where they claim their want to "partner" with physicians to improve the overall health care of the patient.  It is typically advice about drug interactions.  They rarely have the drugs right and never have the accurate prescribing physicians correct.  Is this how "partnering" improves my health?  Was she just bluffing to keep insurance company money off the table?  Are big retail pharmacies that intimidated by managed care?

I didn't have time to figure it out.  The snow was still coming down and there was a question about whether or not I was going to make it with four wheel drive.  An hour and a half later I pulled up to the pharmacy drive through and picked up a thoroughly stapled bag containing the vials.  I tore it open in the parking lot and my suspicions were confirmed.  There was another box of 25 - 3 ml vials, not the 75 I had requested or the "75 vials" that my physician was supposed to have ordered.  Two days of work going through the most sophisticated electronic health record available and nothing had changed.

This is one isolated example of a sequence of events that probably repeats itself tens of thousands of times per day.  It doesn't take much to realize that the combination of obstacles and ineffective medications that occurs by this process is a windfall for both the managed care industry and the pharmaceutical industry.  If you decide that you want to investigate it and find out exactly what went wrong, that is a full time job.  If you want to file a complaint with the state (What - a wheezing asthmatic needs nebulizer solution?) you may not ever be able to get that accomplished.  From working both sides of the prescription process, all that I know is the system is set up to obstruct care.  These unnecessary processes waste everyone's time and money.  It doesn't matter if there is an electronic health record if it means the patient is driving 40 miles back and forth to the pharmacy per month instead of 10, making another 6 calls through time consuming automated telephone queues and paying another 3 copays.  This activity is all based on the false premise that an electronic health record, an algorithm or a business strategy is more important to your health care in the long run than your physicians input.

Nothing could be further from the truth.  

George Dawson, MD, DFAPA

Supplementary 1:  It is one week since the original post and the pharmacy/insurance company insisting on dispensing me one week of nebulizer solution instead of one month as requested.  I called in for a refill yesterday and asked if it would be for one week or one month.  The pharmacist told me exactly the same thing they did last week - they have to submit a request to my physician for the correct number of ampules.

To briefly review, that request has been made by me four times (twice to MD office by phone and secure e-mail and twice to the pharmacy).  They did tell me I could pick up another weeks worth of the medication while I wait for the larger prescription.  I went ahead and did that and have not heard anything on the other prescription 24 hours later.

The Proud Critics of Psychiatry

I received an e-mail first thing this morning from a person who identified himself as Peter C. Gøtzsche, MD.  It looked official, but if this was not sent by Dr. Gøtzsche, all he has to do is send me an e-mail and I will delete this post.  For those unfamiliar with why he might be sending me e-mails he is the author of the "Psychiatry Gone Astray" post that I critiqued.  The body of the message was straightforward and said:

" Incidentally, I found out that some one has written about you and the way you treated my paper about the 10 myths in psychiatry. See attached"

The attachment read: "Asshole of the Day - George Dawson, MD"  The proud author of that post made this statement after a completely respectful response to him on this blog.

Anyone who has been around the Internet and knows about malicious code would have to be a fool to click on an abusive attachment like this and put their data and identity at risk.  Although this is a very simple message it says a lot about the way people expect to treat psychiatrists and get away with it.  Dr. Gøtzsche had sent me an earlier e-mail saying he had responded to my criticism of his criticism of psychiatry.  At this point I have not read it for various reasons including the low volume of web traffic from the Healy web site, the fact that I have been physically ill and exhausted, and my focus on other areas such as the recent series I am attempting to post on the reality of dangerous drugs.

Implicit in the e-mail is that his original "paper" had been treated poorly.  I put "paper" in quotes here because as far as I am concerned it is a blog post.  Where I come from a paper is published in a referred, peer reviewed journal.  It is certainly possible to get rhetorical criticism against psychiatry published in that format, but even then it would not be beyond criticism.  I also disagree with any implication that his opinions were treated poorly.  It is called arguing and as every scientist, philosopher, and rhetorician knows there are at least two sides to every story.  Practically all of the psychiatry critics don't seem to understand that these arguments can be done without taking things personally and using emotional invective.  What many people don't seem to grasp is that it is also part of the scientific method.  Arguments, theories, speculation, conjectures, etc. all have to withstand scrutiny over time.  Even though every top scientist and mathematician expects these challenges, apparently only the critics of psychiatry consider themselves to be above criticism.

There is an asymmetry to the position that psychiatrists should not object to being criticized no matter how irrational, unscientific, or personal the criticism is.  The implicit contention here is that the blog post was "treated" poorly but what about the way psychiatrists are treated and their work with people who have conditions that are treated by nobody else?  And as I pointed out in my original criticisms, why do none of these critics ever look at closely at their own fields and the huge problems that exist there?  

These dynamics are why there is such a blizzard of unscientific and unreliable criticism of psychiatry on the Internet and in the popular press.  This is what happens if you are a psychiatrist who dares to speak out against it and not get into the usual patterns of silence or taking the position that you are somehow better than your colleagues.

My message to these people, no matter who they are is quite simple.  If I have not been deterred by 35 years of irrational and mean spirited criticism - name calling is certainly not going to stop me now.

So to all of the proud critics of psychiatry - flame away!  But don't expect me to engage you in a "debate".  Anyone with an ounce of self respect knows that is not what is going on here.

George Dawson, MD, DFAPA 


  

Supplementary 1:  The other important disclosure that I have relative to the critics is that I have no conflict of interest or appearance of conflict of interest.  I have no book to sell.  I am not invested in pharmaceutical or medical device makers apart from mutual funds where I have no control over the investment decisions.  I have never been paid for my commentary or writing and don't see that ever happening.  I am not a paid spokesman for any commercial or professional organization.  This is a completely noncommercial blog with no advertising.  If I post copyrighted material here I have to pay for those rights out of my own pocket.  I have no relationships with any pharmaceutical companies. I do not consider myself to be a celebrity and I am therefore not trying to enhance my celebrity status and in fact will be he first to admit that hardly anybody reads this blog.  This entire blog is written in my spare time and yes I have a day job.  I encourage a similar analysis of any critic of psychiatry you might be listening to.
  

Dangerous Medications - Part One

Some of the most common rhetoric used against psychiatrists is that the drugs that psychiatrists prescribe are somehow more dangerous than other drugs.  There are numerous problems with the argument including the fact that psychiatrists don't really influence what medications are approved by regulators and the majority of the so-called psychotropic medications (up to 80%) are prescribed by primary care physicians.  There are the associated arguments that they are overprescribed and ineffective and I will address those at another time.  What is the evidence about dangerousness?  I have previously commented on the issue of whether or not the medications used by our field cause a person to become homicidal.  I will restrict this post just to the issue of medication complications and whether or not regulatory action needs to be taken against a medication.

The areas of pharmacovigilance and  pharmacoepidemiology offer some insights into the area of drug dangerousness, but at this point there are few good studies available in public access formats.  One study done in Wales showed that over a 5 year period there were about 100,000 incident reports related to medications or about 9.7% of all patient safety incidents.  The incidents resulted in severe harm or death in 822 patients (0.9%) of the medication related incidents.  The majority of reports were skewed toward reports from hospitals (75%) as opposed to primary care clinics.  Looking only at the severe and fatal outcomes by drug class (Table 8) 2/13 drugs could be classified as medications used to treat mental illness.  Benzodiazepines and antipsychotics were ranked 6th and 12th respectively.  The top 5 drugs starting with number one were opioids,  antibiotics, warfarin, heparin, and insulin.  Any physician working on hospital safety committees is aware of the number of complications due to anticoagulation.  To add further context the total population of Wales in 2011 was about 3 million people, but the total prescriptions per drug class or the critical denominator to determine any true complication rate is unknown.

Unfortunately in the US, we have no complete systems for pharmacovigilance.  We have a long standing data base that has been around for decades that was used primarily to monitor physicians prescribing practices for pharmaceutical companies.  Pharmaceutical representatives would detail physicians (introduce product information) and this company would sell the information about whether the detailing resulted in increased prescriptions of that product.  Occasionally data from this large data base makes it out into the medical literature, but there is a serious question about how well marketing information works for pharmacovigilance.  There is publicly available data from the Centers for Disease Control (CDC) indicating that there are about 50,000 deaths per year attributable to medications.  The majority of these deaths are accidental and intentional overdoses and there is no granularity to look at common severe side effects like anaphylaxis.  A third source of data is proprietary databases from health care companies, hospitals, and government agencies.  Those sources often lead to questions about the generalizability of the conclusions from those studies.

A potentially useful regulatory measure is the number of medications that have been identified as problematic in post marketing surveillance and removed from the market for safety reasons.  The best review I could find on that topic is reference 2.  The paper looks at market withdrawals of new molecular entities (NMEs) approved by the FDA between the years 1980 and 2009.  Of a total of 740 NMEs during that period, 118 (15.9%) were discontinued.  Twenty six drugs out of 118 were withdrawn due to safety reasons or a total of 3.5% of the original approvals.  Nervous system drugs represented a total 104/740 approved drugs and a total of 6.7% of the discontinuations as a percentage of the approvals.  Safety withdrawals were a total of 3 drugs or 2.9% of the total approvals in this therapeutic class.  The bottom line is that a total of 1 drug used for psychiatric indications out of 740 NMEs in the last 3 decades was a medication was withdrawn for safety reasons.

The authors go on to provide a high degree of granularity with a complete list of all NMEs that were withdrawn for safety reasons and they are listed in Table 3.  The three nervous system drugs listed are nomifensine (an antidepressant), levomethadyl acetate ( a drug used to treat opioid dependence), and pergolide mesylate (a drug used to treat Parkinson's Disease and restless leg syndrome).  The  study apparently does not look at the issue of drugs where the manufacturer voluntarily discontinued sales.  As an example, Bristol Myers Squibb discontinued sales of Serzone (nefazodone) in 2003 due to a low incidence of hepatotoxicity with serious outcomes like liver failure and the need for transplantation.   The conclusion of this article is that the majority of of drug discontinuations are due to commercial reasons and not safety.  They noted a trend for decreasing NMEs over time and an associated decrease in drug discontinuations.

Part of the problem with the perception of drug dangerousness, especially with medications used for psychiatric indications seems to be the idea that they should be devoid of side effects.  That is certainly the ideal scenario, but that is not the approach taken by regulatory bodies like the FDA.  Like any regulatory body that depends on politicians for funding there will always be a variety of political influences.  In some cases the bureaucratic structure may be prioritized over scientific review.  The paper by Qureshi, et al is a good example of a certain threshold of severe side effects that may lead to drug discontinuations for those reasons, but any inspection of current approved medications and their rare but serious side effects shows that there are plenty of concerns out there for commonly prescribed drugs in all classes.  The regulatory concern is that many of these medications are useful for the people who really need them.  When any medication is applied over a population of people, there is a likelihood of rare but very serious side effects.  That is not a reason to call the drug dangerous, especially if there are people who benefit from taking it.  There is also a likelihood of common side effects that are less dangerous but adversely impact quality of life.  It is also easy to see the problem politically.  In other words there is some kind of conspiracy driving the prescription of some medications as opposed to others.

The reality is that the patient has a decision to make and as I have pointed out before, I have really never encountered a person (including myself as a patient) who takes that decision lightly.  There are additional interpersonal and psychological factors.  My personal bias as a physician is that the primary goal of treatment is minimal to no side effects and that tolerating side effects is a decision made by the patient but informed by the physician.  It always needs to be balanced against any therapeutic effect of the medication.  


George Dawson, MD, DFAPA:

1:  Cousins DH, Gerrett D, Warner B. A review of medication incidents reported to the National Reporting and Learning System in England and Wales over 6 years (2005-2010). Br J Clin Pharmacol. 2012 Oct;74(4):597-604. doi:10.1111/j.1365-2125.2011.04166.x. Review. PubMed PMID: 22188210; PubMed Central PMCID: PMC3477327.

2:  Qureshi ZP, Seoane-Vazquez E, Rodriguez-Monguio R, Stevenson KB, Szeinbach SL.  Market withdrawal of new molecular entities approved in the United States from  1980 to 2009. Pharmacoepidemiol Drug Saf. 2011 Jul;20(7):772-7. doi: 10.1002/pds.2155. Epub 2011 May 14. PubMed PMID: 21574210