A Neanderthal - Further Confirmation And Much More On Personal DNA

I like the idea of getting my own DNA analyzed and studying the results.  In an earlier post, I described some results of an analysis through a National Geographic project, and the finding that 2.5% of my DNA was from Neanderthals.  The ability to sequence ancient DNA is a relatively new capability and in the few years that it has been done, it has yielded a number of significant findings.  The applicability to the field of psychiatry is limited at this time to 2 references (1,2).  An additional search on ancient DNA and psychiatry yields 4 additional references (4-6) looking at the early origins of mutation and how the associated disrupted regulatory mechanisms could lead to psychopathology.  One of the susceptibility markers for schizophrenia dates back to the last glacial maximum or 24,500 years BCE.  

After trying out the National Geographic site,  I decided to see if the 23andMe site had anything more to offer.  I pulled up their web site, paid the fee and they sent me a sampling kit.  Their sampling technology if different in that they use a tube of saliva as the sample rather than a scraping from the buccal mucosa.  They send you a number of e-mail updates and finally a notification that your DNA has been processed and the necessary reports have been generated.  There are 67 reports in all that focus on ancestry, carrier status, wellness, and traits.  Some reports are more useful than others.  For example it is interesting that a 4th digit on the hand longer than the second digit or a second toe longer than the great toe are inherited characteristics with certain probabilities.  Unless there are some additional health implications involved I don't really care about my longest toe or finger.  The data I am looking for is precisely the data that the FDA told 23andMe that it should not market in the first place.  That initial FDA warning looks at the testing that the company was offering.  In this document the abbreviation PGS is used for "Personal Genome Service":

"Some of the uses for which PGS is intended are particularly concerning, such as assessments for BRCA-related genetic risk and drug responses (e.g., warfarin sensitivity, clopidogrel response, and 5-fluorouracil toxicity) because of the potential health consequences that could result from false positive or false negative assessments for high-risk indications such as these. For instance, if the BRCA-related risk assessment for breast or ovarian cancer reports a false positive, it could lead a patient to undergo prophylactic surgery, chemoprevention, intensive screening, or other morbidity-inducing actions, while a false negative could result in a failure to recognize an actual risk that may exist......."

I am sure there are plenty of posts around the Internet on the regulatory aspects of DNA testing and what the FDA is doing to protect the American public.  23andMe does have consistent qualifying statements saying that none of the data is for medical purposes, only for research and education.  My interest is purely personal research and education.  What more can I learn about DNA, genetics, molecular biology and human diseases.  As noted in my original, what more can I learn about my ancestry and the fascinating subject of Paleogenetics and the associated big questions like why is Homo sapiens - the genus and species of all current human beings the only surviving Homo genus.  Why are all of the others extinct?  I also think that it is quite instructive to remind ourselves that as members of that species we all started out in East Africa and migrated all over the world.

Looking at the test results from the 23and Me analysis, there are four major categories and some are more useful than others.  Those categories include ancestry, traits,  carrier status, and wellness.  Since ancestry was the focus of the National Geographic experiment I took a look at that report first.  In terms of methodology the 23and Me technology looks at overlapping regions of DNA and homology with comparison regions of known ethnic groups.  I prepared the following table to look at the predictive value of the 23andMe approach compared with the National Geographic technique looking at the purported ancestries of my grandparents. (click on any graphic to enlarge)  

As noted in the above table, there is more coverage of ethnicities, using the 23andMe approach with  the best example being that it picks up Norwegian, Swedish, and Dutch markers that were not present in the NatGeo analysis.  There are a few problems that might not be obvious at first.  The test subject does complete information about ethnicities and populations of origin that may be incorporated into the algorithm that assigns probabilities of certain ancestry.  These questions reminded me of the clinical data required for quantitative electroencephalogram machines in the 1990s.  The algorithms were supposed to predict psychiatric diagnoses, but the clinical data that was required with every test, frequently interfered with what the machine was going to select.  I take a very dim view of what appear to be scientific decisions being made on the basis of added speculative data.   The ancestry interpretations also depend the level of confidence assigned to the analysis.  As an example, take a look at the following genealogy assessments - the top a conservative estimate and the bottom much more speculation.  Significant changes in the analysis occur just based on how speculative the analysis is.  All things considered, I am quite interested in the range of the analysis and all correlations at this point rather than precision, but is some cases precision is apparently available.         

All together there are 3 ancestry reports and the most interesting report for me was the Neanderthal analysis.  The test looks at 1,436 traits across the genome and generates a report based on a map of all 23 chromosomes and a table that takes a more detailed look several markers.

The traits report was significantly less interesting to me.  It answered the question about whether or not a genetic markers for a trait existed.  For example, the length of the second toe on the foot and the length of the fourth finger on the hand.  The testing predicts that I have a 96% chance of lighter skin and very little chance of freckling.  That is true.

Carrier status was similarly not very interesting.  There was a major focus on congenital illness rather than risk of chronic illness.  Some of the carrier states mentioned include: ARSACS, Agenesis of the Corpus Callosum With Peripheral neuropathy(ACCPN),  Autosomal Recessive Polycystic Kidney Disease (ARPKD) and 33 others.  My carrier status for these relatively rare conditions was negative.  That was really no surprise considering my age, family history, and the fact that most of these are illnesses of infancy or childhood.

The wellness section contained 6 reports and a few were moderately interesting.  Caffeine consumption is regulated by variants near the CYP1A2 and AHR genes and I have those variants.  The prevalence of these variants in various populations are also estimated and it seem that these variants are high.  I do tend to consume significant amounts of caffeine and it is hardly noticeable.  It seems like I am drinking decaffeinated beverages.  I have the rs73598374 variant in the ADA gene that is associated with deep sleep.  I do sleep for short periods of time, but my activity monitor suggests that my sleep may be deeper than people who sleep more hours.  I also have the rs3923809 variant in the BTBD9 gene that predicts more movement in sleep.  The R577X variant in the ACTN3 gene is present and that is associated with a greater portion of fast twitch muscle fibers or what the site refers to as sprinter/power muscle type.  The final two wellness traits were lactose intolerance and the alcohol flushing reaction.  I knew that I had neither trait prior to the genetic testing.

Apart from the Neanderthal testing, the most interesting aspect of the this service is that ability to search your genome looking for points of interest.  I think that this will eventually be the most interesting aspect of these services as long as the users keep in mind that having a genotype, especially of a complex polygenic illness is a probability statement rather than a guarantee.  I am testing out two ways to do these searches.  The first strategy is based on protein analysis and I used a recent paper on bipolar disorder (I have a strong family history) to see if I could find any of these markers.  The original paper suggests that there are higher plasma concentrations of 6 proteins in bipolar disorder including GDF-15, HPX, HPN, MMP-7, RBP-4, and TTR.  A direct search yields a significant number of hits for HPX (5), HPN (14), and TTR (89) genes with specific information on markers, genomic position, possible variants and genotype.  In this case the original paper was a protein analysis and as far as I can tell there is no genetic analysis of the subgroup with higher levels of the identified proteins.  I have sent an e-mail to the lead author to see if I missed any papers on that issue.  An example of the data available searching on these proteins for the HPX protein is shown below:

The second option would be to search for known genotypes.  It is no secret from previous posts that I have asthma that was quiescent for most of my life that was reactivated about 3 years ago by a upper respiratory infection.  Asthma is an interesting disorder because the genetics are very complex just like psychiatric disorders.  For the critics who suggest that there are no tests of any sort for psychiatric disorders, these two sentences are from the latest chapter on the genetics of asthma from UpToDate (9) are instructive:

"Exploration of the genetics of asthma has also been hampered by the fact that there is no "gold standard" diagnostic test for asthma, and the clinical diagnosis is inconsistently applied.  To circumvent these issues, investigators have studied the distribution of asthma-related traits, including bronchial hyperresponsiveness and measures of atopy (eg, total serum IgE levels, skin test reactivity) in addition to the presence of an asthma diagnosis."

This same author reviews the genetic research on asthma to date and points out that prior to the retirement of the Genetic Association Database in 2014 there were over 500 genetic association studies on asthma that identified hundreds of candidate genes for asthma.  From those candidate gene studies, she gives the most replicated genes as filaggrin (FLG) - an epithelial barrier gene also important in atopic dermatitis,  ORMDL3 - a transmembrane protein, Beta-2 adrenergic receptor gene, and Interleukin-4 receptor gene.  Genome-wide association studies (GWAS) have supplanted candidate gene studies and over 50 GWAS have been done in asthma.  These studies have identified other candidate genes and generally shown that GWAS done in populations with European ancestry seem to have little applicability in more ethnically diverse populations.  ORMDL3 was identified in both types of studies so I searched for that in my own DNA and came up with the following:

            
In order to look at specific markers and asthma risk, I searched on one of the genotyped markers (rs8076131) in PubMed and came up with 7 papers on asthma susceptibility.  Searching more broadly on ORMDL3 showed 132 references that were less specific.

This ends my preliminary review on the availability of personal genomics for education and research purposes by individuals.  I hope to come up with more effective strategies to look at several additional disease phenotypes that I either personally possess or that were present in my first degree relatives.  For me, the paleogenetics and personal genome browsing were the most interesting aspects of this data.  For educational purposes, it highlights the difficulties of correlating genetics with disease phenotypes due in part to the fact that multiple genes and polygenes can produce the same phenotype and that makes the activity of specific genes difficult to determine in a DNA sample.



George Dawson, MD, DLFAPA

      



References:

1:  Srinivasan S, Bettella F, Mattingsdal M, Wang Y, Witoelar A, Schork AJ, Thompson WK, Zuber V; Schizophrenia Working Group of the Psychiatric Genomics Consortium, The International Headache Genetics Consortium, Winsvold BS, Zwart JA, Collier DA, Desikan RS, Melle I, Werge T, Dale AM, Djurovic S, Andreassen OA. Genetic Markers of Human Evolution Are Enriched in Schizophrenia. Biol Psychiatry. 2015 Oct 21. pii: S0006-3223(15)00855-0. doi: 10.1016/j.biopsych.2015.10.009. [Epub ahead of print] PubMed PMID: 26681495.

2:  Mariotti M, Smith TF, Sudmant PH, Goldberger G. Pseudogenization of testis-specific Lfg5 predates human/Neanderthal divergence. J Hum Genet. 2014 May;59(5):288-91. doi: 10.1038/jhg.2014.6. Epub 2014 Mar 6. PubMed PMID: 24599118.

3:  Sipahi L, Uddin M, Hou ZC, Aiello AE, Koenen KC, Galea S, Wildman DE. Ancient evolutionary origins of epigenetic regulation associated with posttraumatic stress disorder. Front Hum Neurosci. 2014 May 13;8:284. doi: 10.3389/fnhum.2014.00284. eCollection 2014. PubMed PMID: 24860472; PubMed Central PMCID: PMC4026723.

 4:  Zhang W, Tang J, Zhang AM, Peng MS, Xie HB, Tan L, Xu L, Zhang YP, Chen X, Yao YG. A matrilineal genetic legacy from the last glacial maximum confers susceptibility to schizophrenia in Han Chinese. J Genet Genomics. 2014 Jul 20;41(7):397-407. doi: 10.1016/j.jgg.2014.05.004. Epub 2014 Jun 2. PubMed PMID: 25064678. 

 5:  Cotney J, Muhle RA, Sanders SJ, Liu L, Willsey AJ, Niu W, Liu W, Klei L, Lei J, Yin J, Reilly SK, Tebbenkamp AT, Bichsel C, Pletikos M, Sestan N, Roeder K, State MW, Devlin B, Noonan JP. The autism-associated chromatin modifier CHD8 regulates other autism risk genes during human neurodevelopment. Nat Commun. 2015 Mar 10;6:6404. doi: 10.1038/ncomms7404. PubMed PMID: 25752243; PubMed Central PMCID: PMC4355952. 

 6:  Toyota T, Yoshitsugu K, Ebihara M, Yamada K, Ohba H, Fukasawa M, Minabe Y, Nakamura K, Sekine Y, Takei N, Suzuki K, Itokawa M, Meerabux JM, Iwayama-Shigeno Y, Tomaru Y, Shimizu H, Hattori E, Mori N, Yoshikawa T. Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B. Hum Mol Genet. 2004 Mar 1;13(5):551-61. Epub 2004 Jan 6. PubMed PMID: 14709596.

7:  FDA Warning Letter to 23andMe

8:  Frye MA, Nassan M, Jenkins GD, Kung S, Veldic M, Palmer BA, Feeder SE, Tye SJ, Choi DS, Biernacka JM. Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders. Transl Psychiatry. 2015 Dec 8;5:e689. doi: 10.1038/tp.2015.185. PubMed PMID: 26645624.

9:  Barnes KC.  Genetics of Asthma. In: UpToDate, Barnes PJ, Raby BA, Hollingsworth H (Ed), UpToDate, Waltham, MA. (Accessed on April 8, 2016)


Attributions:

All of the above graphics and tables with the sole exception the the ancestry table were generated with on site software at 23andMe based on my personal DNA sample.

Say What You Mean.........

I read an elegant editorial piece during breakfast this morning.  It was in the regular section in JAMA called "A Piece Of My Mind".  Amanda Fantrey, MD writes about some of the insights she developed as a family member in an ICU setting after her brother was involved in a motor vehicle accident and sustained a traumatic brain injury and coma.  She describes the pull on doctors to make statements that offer hope and frequently diverge from the realistic medical appraisal of the situation.  She describes this as "the seismic gap between what was said by staff (both physicians and nurses) and what was heard by family."  A common example is the staff remembering the one patient with a miraculous recovery and bringing that up in discussions with the family as a way to give them hope.  Dr. Fantrey points out the origins of this behavior as wanting to reassure a traumatized and grieving family.  She gives a clear example of how this plays out in a discussion between the neurosurgical team and her parents.  What seems like a grim prognosis is suddenly being moderated by qualifiers. With enough modification the initial grim prognosis becomes the expectation of recovery.  She also points out that another level this is self preservation - a bias toward recalling the miracle cases and saves.  That without it practicing medicine and surgery is just too grim to contemplate.  This is an excellent essay that I would recommend to any medical student or resident as an example of the power of affective communication, language, and interpersonal dynamics.

The interactions that Dr. Fantrey describes on medicine are common.  I think they form the basis for a number of commonly observed phenomenon.  Psychiatric practice is no exception.  The first thing that came to mind is the promise of the miracle drug that will take away all of your problems.  Many psychiatrists witness first hand patients who explicitly ask them for this kind of medication.  Many people become addicted to opioids because at the outset - it seems like these medications have the properties of an ideal medication.  There has been abundant criticism that new medications are oversold both by advertising and the way that advertising affects the pharmacology literature.  I am much less certain of that as there is more evidence accumulating that the pricing power of the companies themselves is the single largest factor driving much higher pharmaceutical prices and profits in the US.  There is the inescapable sense of hope being conveyed through both direct-to-consumer advertising and and the novelty of a new drug.  Although it has not been adequately tested, that new drug is a form of hope in a pill.  The interested people are all hoping for better therapeutic effects even in spite of the rapid delivery of a list of serious side effects "including death" at the very end of the commercial.

It also brought to mind some of the serious discussions that psychiatrists have with patients and how the biases might be a little different.  The most obvious one is lithium.  Lithium is one of the best medications in terms of therapeutic effects that psychiatrists prescribe.  The attitude of other physicians seems to be: "We will let them prescribe that medication almost exclusively" or "You psychiatrists sure do prescribe a lot of toxic medications."  Treating people with the most severe forms of mental illness almost exclusively for 30 years has caused me to witness many miracles of lithium therapy.  The commonest was the depressed bipolar patient not able to eat, barely taking in fluids, and certainly not able to function outside of a hospital setting.  After starting lithium, many of of these folks recover enough function within a week to be up in the daytime, eating and starting to care for themselves.  For me the miracle of lithium has been on the depressed side.  People who have failed antidepressants and whatever anticonvulsant is en vogue for bipolar disorder.

There is no other medication prescribed by psychiatrists that invokes fantasies and expectations more to patients than lithium.  Their expectations are generally very bad as in:  "That is some serious shit - dude..  Isn't that the medicine in that song......"  I have to remind people that the band was Nirvana and yes I am old enough to have watched them perform the song Lithium live on Saturday Night Live.  I have to explain calmly that it is a salt and that this makes it a unique kind of medicine with fairly unique precautions but that is can be safely taken.  I do point out that is if they end up taking it for decades or if they have repeated episodes of lithium toxicity - it can cause renal failure in some and the need for dialysis and renal transplantation.  I know this because of my experience with end stage renal disease that was attributed to lithium by my Renal Medicine consultants and the protracted course of dialysis, in some cases delirium, and ultimately renal transplantation.  I try to outline all of that, but it is hard to imagine how much information is getting through.  Like Dr. Fantrey's ICU experiences, nobody is more acutely aware of needing to provide hope than a psychiatrist talking directly to a depressed bipolar patient.  We are simultaneously assessing suicide risk - even in inpatient settings.  Acute care psychiatrists know that this is our job.  We have to keep this person alive so that they can recover.

I have to cautiously present the information on lithium as part of the informed consent discussion, but at some point I also started to include a line about lithium being a "potentially life-changing medication."  I explain that the person may experience mood stability like they have never had on the endless series of antidepressants, atypical antipsychotics, benzodiazepines, various anticonvulsants and the drift toward an inaccurate schizoaffective disorder diagnosis that they have been experiencing for years or decades.  I am always concerned about whether they hear the word potentially in my description.   I provide them with a detailed handout on lithium and encourage them to do whatever research they would like to do on the medication and I will answer any further questions.  Is this just another example of hope enacted in the countertransference, me trying to convey it to a desperate patient?  It is hard to imagine that patients who view lithium as a toxin at the outset could have unrealistic expectations about the drug.  Am I coloring their expectations by my description of the drug?  Would it be unfair to not include that information about potentially changing their life?

I think there are problems with all complex informed consent discussions.  These discussions can't be devoid of emotional content.  Like the surgical patients, some people will do better and some will do worse.  It is difficult to determine that ahead of time.  Every patient I see needs to benefit from my experience treating other patients.  And with lithium it is very good.  


George Dawson, MD, DFAPA


References:

Fantry A. Say What You Mean, Mean What You Say. JAMA. 2016;315(13):1337-1338. doi:10.1001/jama.2015.18910.






 

POTUS Tweets Measures To Address Opioid Epidemic

In 2014, nearly 21,000 deaths in the U.S. involved prescription opioids. Here's what @POTUS is doing about it: https://t.co/M2HgnDDN6a

— The White House (@WhiteHouse) March 29, 2016

I happened to be on Twitter last night when I caught the above Tweet from POTUS.  Having a professional interest, I decided to follow the link at the White House blog to look at the proposed measures.  They were listed as:

1.  Increasing a key drug for medication assisted treatment.  That key drug is buprenorphine in a number of formulations for treating severe opioid dependence.

2.  Preventing opioid overdose deaths.  This appears to be $11 million in funding for various forms of treatment and increasing access to naloxone to reverse the effects of an acute overdose.

3.  Addressing substance use disorder parity with other medical and surgical conditions.

These are very modest and in some cases unrealistic proposals about about trying to stop a drug epidemic that is killing 20,000 people a year.  Let me tell you why:

1.  Increasing a key drug for medication assisted treatment.  That key drug is buprenorphine in a number of formulations for treating severe opioid dependence.

Buprenorphine as Suboxone and Subutex have been available for the treatment of opioid addiction in the US since 2002.  The current evidence suggests that buprenorphine has superior efficacy for abstinence from opioids and retention in treatment.  There is also evidence that patients on buprenorphine have fewer side effects and that they is a less severe neonatal abstinence syndrome in mothers maintained on buprenorphine versus methadone.   Buprenorphine is also used for acute detoxification and treatment of chronic pain.  One of the limitations of maintaining opioid addicts on buprenorphine is that a special license is required to prescribe it.  Physicians can obtain that license by by attending CME or online courses.  Even then, expansion to primary care physicians has been slow because they may have no colleagues in their practice with similar certification and that makes on call coverage problematic.  In addition, many clinics that are medically based are reluctant to provide this type of service to people who have opioid addictions.  Apart from the technical requirements of prescribing the various preparations of buprenorphine certain physician and patient characteristics may also be important.  Physicians have to be neutral and not overreact in situations where the patient exhibits expected addictive behaviors that may include relapse.  As an example, younger opioid users are frequently ambivalent about quitting and in some cases, use other opioids and reserve the buprenorphine for when their usual supply dries up.  They may sell their buprenorphine prescription and purchase opioids off the street.  It may not be obvious but physicians prescribing this drug need an interpersonal strategy on how they are going to approach these problems.    On the patient side,  there is the biology of how the opioids have affected the person.  Do they have severe withdrawal and ongoing cravings?  What is their attitude about taking a medication on an intermediate or long term basis in order to treat treat the opiate addiction?

In clinical trials, buprenorphine seems to be ideal medication for medication assisted treatment (MAT) of opioid dependence.  Like most medications, there are issues in clinical practice that are not answered and possibly may never be answered.  The issue of life-long maintenance is one.  Many people with addictions are concerned over this prospect.  Long term maintenance with buprenorphine has advantages over methadone in that it is easier to get a prescription rather than show up in a clinic every day to get a dose of methadone.  Most addicts are aware of the fact that withdrawal from both compounds can be long and painful.  This deters some people from trying it and relapse risk is high if a person attempts to taper off of it.  Despite the current consensus about use. there is still the problem of young addicts who feel that they are "not done using" and who go between using heroin and other opioids obtained from non-medical sources and buprenorphine.  

2.  Preventing opioid overdose deaths.  This appears to be $11 million in funding for various forms of treatment and increasing access to naloxone to reverse the effects of an acute overdose.

Naloxone kits that would allow for rapid reversal of opioid overdoses have been shown to be effective in partially decreasing the death rate.  At some treatment and correctional facilities opioid users are discharged with naloxone kits for administration in the event of an overdose.  Opioids are dangerous drugs in overdose because they suppress respiration and that can lead to a cardiac arrest.  There are several properties of opioids that heighten the overdose risk.  Tolerance phenomena means that the user eventually becomes tolerant to the euphorigenic and in some cases therapeutic effects of opioids and needs to take more drug.  If tolerance is lost when the user is not taking high doses for a while, using that same high dose can result in an overdose.  Taking poorly characterized powders and unlabelled pills acquired from non-medical sources compounds the problem.  The exact quantity of opioid being used is frequently unknown.  Adulterants like fentanyl - a much more potent opioid can also lead to overdoses when users do not expect a more potent drug.

In addition to the pharmacology of the drugs being used there is also a psychological aspect to overdoses.  Users often get to the point where they don't really care how much they are using in order to get high.  They will say that they are not intentionally trying to overdose, but if it happens they don't care.

The available literature on making naloxone available suggests that it is effective for reversing overdoses in a fraction of the at risk population that it is given to.  I would see at as the equivalent of an Epi-pen in that the majority of patients with anaphylactic reactions get these pens refilled from year to year but never use them.  When they are required they are life-saving.  The problem with a naloxone kit is that it assumes a user or bystander can recognize an overdose and administer naloxone fast enough to reverse the effects of opioids before the user experiences serious consequences.  Unfortunately addiction often leads to social isolation and not having a person available makes monitoring for overdoses much more problematic.  Naloxone kits should always be available opioid users, first responders, family members, and anyone involved in assisting addicts.  Detailed long term data on the outcomes over time is needed.  

3.  Addressing substance use disorder parity with other medical and surgical conditions.

The is the most critical aspect of the President's tweet.  One of the main reasons for this blog is to point out how people with addictions and severe mental illnesses have been disproportionately rationed since the very first days of managed care - now about 35 years ago.  Some of the first major changes involved moving medical detoxification out of hospitals.  So-called social detoxification was available with no medical supervision.  These non-medical detox facilities were very unevenly distributed with only a small fraction of the counties in any state running them.  Any admissions to hospitals were brief and "managed" by managed care companies.  In the case of addictions some of the management practices were absurd.  A standard practice was to determine how many days a person could be in residential treatment.  That often required a call to an insurance company nurse or doctor who had never seen the patient.  They could determine that the patient could be discharged at any time based on arbitrary criteria.  In some cases that involved just a few days and the patient was leaving with active cravings and in some cases an an active psychiatric disorder.  This practice continues today, despite party legislation that suggests that addictions and mental disorders should be treated like any other medical problem.

This is where the President's tweet is on very shaky ground.  His legislation  focuses on large systems of health care and yet these systems don't seem to be able to supply adequate treatment with either buprenorphine or naloxone kits.  The President is fully aware of the The Paul Wellstone and Pete Domenici Mental Health Parity and Addiction Equity Act of 2008 (MHPAEA).  That act was supposed to provide equal treatment for mental illnesses and addictions that was on par with medical and surgical conditions.  I think it is no secret that special interests have shredded the intent of this bill to the point that it is useless.  Managed care systems still ration care for these disorders in their best financial interest.  The resources for treating these disorders are still not equal to the task. In the case of prescription painkillers the same system of care not providing adequate treatment for addiction is often where that addiction started.

All three of the President's points could be addressed by forcing health care companies to provide adequate care for addictions and mental illnesses instead of grants to provide services that they should be doing in the first place.  In an interesting recent twist the President (1) suggested that this discrimination was based on race.  He implied that as a result the police rather than doctors have been used to address the problem.

Let me be the first to say that President Obama is wrong.  There is no doubt that racial discrimination exists.  There is no doubt that it occurs in systems of health care (2,3).  There is also no doubt that all it takes is a diagnosis of addiction or mental illness to trigger highly discriminatory health care coverage - irrespective of a person's race.  It is all about how health care businesses make money in this country by rationing or denying treatment for these disorders.

To reverse that discrimination,  the government needs to take the MHPAEA seriously.  So far they have failed miserably and that is the problem on the treatment side in trying to address the opioid epidemic.  

George Dawson, MD, DLFAPA

References:

1:  Sarah Ferris.  Obama: 'We have to be honest' about race in drug addiction debate.  The Hill March 29, 2016.

2:   Eddie L. Greene, MD and Charles R. Thomas, Jr, MD.  Minority Health and Disparities-Related Issues: Part I.  Medical Clinics of North America July 2005; 89(4).

3:   Eddie L. Greene, MD and Charles R. Thomas, Jr, MD.  Minority Health and Disparities-Related Issues: Part II.  Medical Clinics of North America July 2005; 89(5).

  

Dr.Ghaemi on Dr. Spitzer

Nassir Ghaemi, MD has a commentary on Robert Spitzer, MD in this month's Clinical Psychiatry News.  After citing quotes by Shakespeare and John Adams to suggest that the dead are often idealized, he settles down to criticism based on whether or not the DSM-III helped or harmed the profession and Spitzer's role in that process.  Ghaemi comes down firmly on the side of harm because an unscientific approach to the diagnostic criteria for major depressive disorder has resulted in a lack of reliability and validity.  He uses the often quoted kappa score of 0.32 for diagnostic reliability of major depressive disorder in DSM-5 field trials as the main source of evidence, as well as the fact that the diagnostic criteria are unchanged since DSM-III.

Ghaemi suggests that his viewpoint is unique because unlike other eulogists, he had no personal connection with Spitzer and therefore can speak "in forthright recognition of fact from the impersonal perspective of another generation."  I am closer to Ghaemi's generation than Spitzer's and can make the same claim, but come to an entirely different set of conclusions.

I don't see Spitzer's efforts as being as corrosive as Ghaemi does, probably because I recognize the fact that there will never be a set of written diagnostic criteria that are perfect, based on science, and unambiguous.   But before I address the scientific, let me take on the rhetorical.  I would hardly blame Spitzer for the fact that the DSM criteria for depression have changed "hardly an iota" in the intervening 40 years since DSM-III.  Over that same time span there have been hundreds if not thousands of articles on the reliability of the major depressive episode diagnosis, as well as articles that analyze the symptoms according to that diagnosis.  There have been articles on standardizing various psychiatric and psychological instruments to detect major depression.  In fact, one of the rating scales basically copies the DSM criteria and asks the patient to rate on a 0 to 3 point scale - the percentage of days that they experience the symptoms. The PHQ-9 has become the standard for depression diagnosis in many primary care clinics.  There is also the fact that Spitzer's original DSM-III effort resulted in much higher reliability figures - a kappa of 0.72 to be exact (2).

There is also the issue that there have been two intervening Task Forces for DSM-IV and now DSM-5.   The Chair of the DSM-IV Task Force has since become a prominent critic of the DSM process and psychiatry in general.  I may have missed it, but at the time that Task Force was convened, I did not notice him or other members advocating for major changes to the major depression diagnostic criteria.  These are supposedly the top minds in the field.  Highly motivated academics with one axe or another to grind.  The idea that everyone would defer to Dr. Spitzer based on his original approximate efforts seems unrealistic to me.  More than a few people would have noticed his bungled and unscientific approach.

My major problem is using a single reliability figure as the grounds for this criticism.  Every year outpatient based psychiatrists can see up to a thousand new people a year.  They may find that up to 50% of those patients have had a life-long sleep disturbance.  Many can recall nightmares and sleep terrors as children.  Another 20-30% will have generalized anxiety or social anxiety since childhood.  In some there will be a performance based anxiety that is comorbid with the social anxiety.  Another 10-20% will have post-traumatic stress disorder to some degree.  About one-third will have a significant substance use problem.  These percentages will vary by clinic location and referral base.  The majority will be referred for a diagnosis and treatment recommendations for depression.  A substantial number of people with depression have comorbid anxiety and anxious temperaments.  I don't think it is a stretch to say that on any given day, many of the identified depressives will identify themselves as primarily anxious.  It is not unexpected to find that many patients don't really understand the difference between anxiety and depression or they will overtly say that they are the same problem - indistinguishable from one another.  Unless there is a clear differentiating factor like a manic episode, the postpartum state, or psychotic symptoms I would not expect that anxiety and depression are distinct disorders for most people.  At the minimum anxiety might morph into depression, but in most cases they are coexisting chronic conditions.  A low kappa in this situation should be expected and not a shock.

Does that mean that psychiatrists should be wringing their hands and blaming Spitzer for it?  Neither response is appropriate.  Psychiatrists are highly successful in diagnosing and treating mental illness, not because of a DSM manual, but because of clinical training.  When it comes to anxiety and depression there are no known ways to parse all of the symptomatic possibilities.  The human brain is designed to realize all of the possible combinations of human experience.  Why would we expect it to be different when it comes to experiencing anxiety and depression?  The only chance that a psychiatrist has to make sense of the world is a number of patterns of diagnoses based on their training and practice experience that they can match against the patient they are currently seeing.  These patterns guide the diagnosis and treatment plan.  A clinically astute psychiatrist is not plowing through the interview to see if the patient "meets criteria".  A clinically astute psychiatrist carefully attending to the patient's conscious state and trying to figure out how they can be helpful.  That includes figuring out the real problems and prioritizing them in a complex matrix psychiatric and medical problems.  None of that flows from the DSM and none of that resembles research based on lay people interviews using DSM criteria.

In closing, any commentary on Dr. Spitzer should include his role in eliminating homosexuality from the diagnostic manual.  This detail and how it occurred is never taught to residents.  I had to learn it from public radio many years after residency.  This detail is significant any way you cut it.  It invites criticism that monolithic psychiatry is currently moving too slow in other areas or that monolithic psychiatry was just responding to public pressure.  There is also criticism directed at Dr. Spitzer for a paper based on self report that was withdrawn years later on this same issue.  There are always advocacy groups seeking publicity by their own spin on the issue.   In my opinion, none of that diminishes that significant achievement that put psychiatry four decades ahead of most people in the United States.  Say what you will about the DSM, that accomplishment alone is enough.  I am thankful that Dr. Spitzer was open minded enough to listen to the advocates and eventually side with them.              


George Dawson, MD, DLFAPA


1:  Nassir Ghaemi.  Commentary:  Dr. Robert L. Spitzer - An impersonal appraisal.  Clinical Psychiatry News.  March 2016. p 12-13.

2:  Riskind JH, Beck AT, Berchick RJ, Brown G, Steer RA. Reliability of DSM-III diagnoses for major depression and generalized anxiety disorder using the structured clinical interview for DSM-III. Arch Gen Psychiatry. 1987 Sep;44(9):817-20. PubMed PMID: 3632255.

Opiates And Moral Dilemmas For Physicians

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

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

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

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

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

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

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

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

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

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

      

George Dawson, MD, DLFAPA


Supplementary:

To calculate the mg alcohol in a pint of whiskey:

1 pint = 473.18 ml

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

References:

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

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

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

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

       

The Screeners - Annotated: Psychiatric Lessons From A Short Science Fiction Story

I recommend reading the original version (preceding post) first before reading the annotated version.


What follows actually happened in the year 2066......

I could tell my brother needed help. We had been underground for too long. Whenever that happened he stopped sleeping regularly, he started to act crazy. This time he was looking for footprints - evidence that somebody was trying to get in through the hatch. I explained to him that the hatch was hydraulically locked from the inside. It was designed to take a direct hit from a grenade-launcher. But who could even hit it at that angle, flat against the two foot thick concrete roof of our bunker. This time he was sprinkling flour rations on the floor under the hatch. Anyone who came in had to step on that area and he would have their footprint in the flour.

This is an almost universal experience of family members directly observing their relatives with bipolar disorder.  They notice they become unpredictable sometimes to the point that they are frightening.  This is often manifested in their capacity for rational thought and personality changes.  In this case they observe paranoid behavior - defined as an unrealistic fear of harm or manipulation.  Family members are often at a loss in this situation because the person with the problem denies that there is anything wrong.  In many cases, the personality changes go on for months and lead to problems with employers and spouses.   

But the powder around the entrance was the least of our worries. His apartment was within a hundred feet of the hatch. He sat in his apartment looking out the window. He kept a plasma cutter nearby. It was for self defense, but he also told my son that if anyone did breach the hatch and they came for him - he knew exactly what to do. He would turn the plasma cutter on himself. He did not want to give the invaders a chance to torture and kill him. He would kill himself first. It would be over quickly.

This is a little known form of suicidal thinking that occurs in paranoid people.  They are so fearful of the unknown assailants that they are prepared to kill themselves - rather than be tortured or slowly killed.  In fact, they are not in danger at all.  This problem requires an intense effort to diagnose and treat - independent of any medications.

He had been getting worse for the past ten years. Long periods of laying in bed for days and weeks, barely eating and drinking. Not saying a word. That usually happened after weeks or months of being hyper, talkative and staying up all night. If you caught him at exactly the right time, he was interesting, funny, and you felt good talking with him. At the wrong time - it could be a nightmare. He could accuse you of trying to steal his American Gold Eagles. Everybody knew he had a tube of them somewhere in the bunker. Everybody knew because whenever he got hyper and started talking a lot, he would hold some of the coins in his hands and show everybody that he had them. During one of these episodes, he gave a couple of them away. Gold Eagles worth tens of thousands of dollars - just handed out to strangers at a watering hole.

Very typical behavior of untreated bipolar patients.  During periods of hyperactivity and euphoria they may give away large sums of money to casual acquaintances without being able to assess the consequences.  This can lead to financial duress or in the extreme, financial ruin. 

He had bipolar disorder, just like our mother. He has never seen a doctor, I just know from my experience with my mother. I remember going to see the doctor with her. She would see her every couple of months, unless she was having problems and then it would be more frequently. She liked that doctor and trusted her. She would always tell me that if she got too sick to make it to the doctor, my job was to call the doctor's office and let her know that she was not doing well. The doctor came over to our house one day to see my mother. Mom didn't say much, but the doctor knew what she needed and a short time later she was better. That went on like that for about ten years until I was ready to go to college. That was when the Supervolcano blew and we all had to go underground for three years. Mom was 60 by then. She couldn't adapt to living underground. She could not sleep underground in the phosphorescent lighting. She would stay up for weeks and get harder and harder to understand. She would start swearing and eventually made no sense at all. Then she would crash and not be able to eat. My wife and I would encourage her, but she would say: "Let me die....pick up that knife over there and kill me." We knew that she was not joking. Until the air finally cleared, there were no doctors and no medicines. She only had a month of medication when we went underground. Nobody could get more than a month at a time - even though everybody knew it was going to be a long time before we could come up for air.

Bipolar disorder definitely runs in families with what appears to be sporadic inheritance because of the polygenic nature of the disorder.  Bipolar disorder is sensitive to sleep and circadian rhythm disruptions and patients need to be counseled and constantly reminded about this.  Severe cognitive problems and catatonia can result and lead to severe disability. 

At about the one year mark - Mom died. She just got more and more confused. She stayed in bed and did not eat or drink anything for five days. The paramedic in our bunker said that she probably died from dehydration.

I don't think it is common knowledge that bipolar disorder can be a fatal condition.  At the turn of the 19th century, well before there were any useful medications - some forms of bipolar disorder were highly fatal.  Estimates from Boston Hospitals at around that time suggested that malignant catatonia resulted in about an 80% fatality rate.  Untreated mania in those days also resulted in a significant number of deaths from congestive heart failure due to constant agitation.  These facts are often ignored during an era where even episodic care during exacerbations of illness can prevent death.  Inpatient psychiatrists and consultation-liaison psychiatrists still find themselves in many life and death situations per year with hospitalized patients on the verge of dehydration and starvation due to severe psychiatric disorders.  In many situations, one of the best treatments available for this problem - electroconvulsive therapy is unavailable due to legal and political constraints.   

"Kevin is getting bad again" - my wife walked in. She was wearing standard desert camouflage hardened to withstand all of the fly ash. "I just saw him. He had melted a jar of peanut butter in the microwave and and he was throwing it all over the place. He has it splattered all over the walls. It looks like a Jackson Pollock painting." My wife was going to study art before the Supervolcano or "SV" as some call it now. Most people just talk about surviving it by using the phrase "when the air cleared." "We have to do something before he ends up like your mom or somebody takes advantage of him and gets his gold."

Highlights the familiy predicament of dealing with a family member who has had a transformation of their conscious state.  They are no longer predictable or rational.  Most emergency medical personnel confronted with this situation would ask the person a few questions and leave.  If the person became verbally aggressive, the outcome of the situation is highly dependent on the skill of the emergency personnel or involved law enforcement officers and there can be very adverse outcomes.

"More like hitting him over the head and taking it you mean. You would think that a guy who can be that paranoid would not put himself in those situations." I knew the words were meaningless as soon as they rolled off my lips. I had been watching bipolar people in my family for decades and they are unpredictable. Expect to see them in a certain situation and they disappear for weeks or months. "We have to try to get him to Minneapolis and see if they have scavenged any medication or if any new medical supplies have been flown in."

We had been to Minneapolis a couple of times since the air cleared. The trip is not too bad - 300 miles by a skimmer across the fly ash. So far nothing was growing up through the fly ash. We make good time with a skimmer and the metal composite tires make that trip many times before they need to be replaced. It just takes 20 minutes to recharge the batteries and we are back home the same day. The medical infrastructure was slowly being rebuilt. Practically all of the health care administration in the state was in Minneapolis and many of these bureaucrats survived the near extinction event. Surgical services and Cardiology had been restored. Last year they began doing heart, lung, liver and pancreas transplants at what used to be University Hospital.

There is a long history of discrimination against psychiatric and addiction services, despite the fact that they are routinely assessed as being in the top 10 disabling conditions world wide.  The discrimination is well documented on this blog and it occurs at all levels.  The so-called critics of psychiatry do not mention this phenomenon because it is inconsistent with their view that psychiatry is the source of all problems and not the selective rationing.

Treatment for mental disorders was always a problem. As people started coming out of their bunkers and heading back into the city general medical care was available in many places. The only treatment for mental disorders occurred in the same clinics where people went to get treated for infections and lung problems from the fly ash. People still got cancer and heart disease. People still got involved in accidents and injured themselves. Doctors with various skills were still around even though training programs were just restarting. Doctors tended to be old or really young.

In this piece, collaborative care and its ultimate goal of eliminating psychiatry rules the day.  An interesting proposition is who all of the critics will blame when psychiatrists are gone.  The obvious choice would be the next batch of prescribers, but in my story they became history as well.  There is clear history of mismanagement in medicine - rationalized by "cost effectiveness".  The most cost effective approach is to marginalize all professionals and pretend to replace them with checklists or artificial intelligence. 

My wife and I did some fast talking, convinced Kevin it would be an exciting trip, loaded him in the skimmer and took off. Within 4 hours we were standing in line in a large warehouse that had been converted to a medical clinic. Half an hour later we were face to face with a triage person:

"Nature of the problem?" he said matter of factly.
"My brother has bipolar disorder and he needs treatment." I replied.
"We don't see a lot of that here, are you sure about the diagnosis?" The triage person seemed a little impatient.
"My mother had it and she told me that her grandfather had it. He does a lot of what she used to do. His whole personality changes at times and he has problems taking care of himself. She used to see a doctor who treated bipolar disorder. Do you have a doctor like that?"
"Not anymore...but we do have screeners."

You don't have to live in the year 2066 to experience the above dialogue.  It is occurring right now in hundreds of clinics across America.  No access to psychiatrists or mental health professionals who could be very useful in treating the problems that they were trained to treat. 

We walked to the west side of the warehouse and entered a small room. There were a few people there. We got in to see the screener in a about 20 minutes. He looked like a clone of the triage person right down to the American Health Care pin on his lapel. He listened to me describe the problem for about two or three minutes, reached in a drawer and pulled out a piece of paper. It had three questions on it. After every question there was a line that varied from "None" to "Most of the time." Kevin made three checkmarks - one on each line at about the 75% mark.

This is a standard approach being used right now.  A checklist will be made right out of the DSM criteria.  Then it will be pared down to 3 or even 1 question rating scales.  Without the presence of a diagnostician, the checklist score and cutoff becomes the default diagnosis.  The interesting aspect of a screening instrument for bipolar disorder is that in many cases the affected person will not endorse any problems on the scale even when they are quite symptomatic.  

"Well he qualifies for treatment." the screener remarked. "The Army just brought in a shipment of medication for mood problems."
"My mother used to take Phosphotide 23, before the volcano blew. It worked pretty well."
"No ... all I have is this stuff.   It is taking a while to get drug manufacturing up and running again. Only the west coast facilities were untouched and they have shifted all of their production to what people really need...you know antibiotics, heart meds, asthma medication. But I have plenty of this medication. Give it a try. Take two of these tablets every night".

There are widespread complaints about Big Pharma and medication prices.  I have written several pieces on this blog myself.  Medication expenditures have created a large number of medications and a significant surplus, but they are ironically rationed by Pharmacy Benefit Managers and managed care companies, even to the point that generics drugs require a negotiation.  In this case the patient is being given a medication that is probably not indicated for his condition and may make him worse.  Similar problems can occur with treatment based on screening tests.   

He handed me a large bottle of medication. The darkened label on the bottle read: "amitriptyline 25 mg tabs". The expiration date was July 20, 2025. I looked back at the screener and asked: "Is there anybody he can talk to about some of his problems? He goes off on a tangent and my wife and I don't know what to say to him."

This is a current problem in the business oriented behavioral health system.  Psychotherapy is rationed and in many case therapists have productivity expectations that they cannot sustain and that leads them to quit.  Contrary to popular myths people with severe mental illnesses benefit greatly from talking with their psychiatrists and are often reluctant to see other therapists or physicians.  In many systems of care today patients with severe mental illness see a "prescriber" for 15-20 minutes - 2 - 4 times a year. 

"No I'm afraid not. At American Health Care we do screening. My understanding is that the new government and the remaining businesses got together and decided that was the most cost-effective approach."

"Cost-effective" is a buzzword that is unevenly applied.  That should be evident from comparing psychiatric services (or behavioral health services) to every other medical specialty in any health care system.  There is a sharp contrast between what this concerned family member knows about bipolar disorder (disabling and killing his mother and disabling his brother and making him unpredictable) and how the health care system responds to his concerns.  It is as if  he is talking about a trivial condition.

Within thirty minutes we were back in the skimmer, moving at good speed across the fly ash. I glanced over at my wife. Her large blue mirrored-out glacier glasses did not conceal her worry. I looked at the plume we were kicking up in my rearview screen and thought:

"I hope this works."

Our concerned family member here is hopeful, but it is highly unlikely that the medication he picked up will be effective and it may make the situation worse.  The patient and family would have benefited by a detailed risk-benefit and monitoring discussion, as well as a follow-up plan.  In a typical screening procedure that occurs today, a person may leave the office with one or more month-long prescriptions and no clear plan for monitoring or contingencies if the medication does not work or it is not tolerated.  Follow up periods are frequently too long to make much of a difference and many people either discard the medication immediately, don't get it refilled, or get side effects - don't report them and discard the medication.  More frequent meetings for psychotherapy or closer monitoring are the exception rather than the rule.  

The more I thought about this near apocalyptic science fiction story, the more I realized that this is the type of care that many (if not most) people get right now and it is the type of care that is being promoted over seeing psychiatrists.



George Dawson, MD, DLFAPA


Supplementary:

I tried to write this science fiction piece in the spirit of the one page sci-fi stories that are always on the last page of the journal Nature under their heading Futures Science Fiction go.nature.com/mtoodm

From the perspective of a psychiatrist (and a family member) of course.

This is a pure fiction and it contains no references to any real people or corporations. Any resemblance is purely coincidental.


Attribution:

The picture at the top of this file was uploaded from Wikimedia Commons.  This attribution is from their side and when the file was accessed on March 19, 2016, the link in this reference did not work:  Work of the Bureau of Land Management, a U.S. Government Agency. Taken from the BLM website: http://www.blm.gov/style/medialib/blm/wy/rsfo/recpics.Par.0272.Image.640.427.1.gif  No photo credit is given.