Sunday, February 28, 2016

Psychiatry With And Without A Conscious State



One of the great attractions of psychiatry for me - is the skill set that you have to develop to understand a person's real problems.  By real problems - I mean the problem or problems that brought them in to see you in the first place.  I am not talking about the problem listed on a referral sheet, or spoken in a telephone call, or even described to you by another physician or family member.  Advocacy groups and some psychiatrists tend to be self congratulatory on the amount of information about psychiatric disorders that is out there.  There is an excessive amount of confidence in lists of symptoms being the same thing as a diagnosis.  Any psychiatrist will tell you that the number of people who walk into the office and proclaim they have depression, bipolar disorder, or attention deficit-hyperactivity disorder is at an all time high.  They typically come to that conclusion by some combination of listening to TV ads or friends and family members.  In some cases they are directed to Internet sites where they can take a brief quiz to determine the diagnosis.  In almost all cases they are wrong.  Interviewing people to come up with both diagnoses and diagnostic formulations - is a considerable skill set that cannot be replicated by handing that person a symptom checklist or interviewing them like a talking checklist.

The problem in cases of self-diagnosis is that most people have a limited awareness of what diagnosable mental illness is.  They get their ideas from a static checklist or advice from a person who has not seen hundreds of people with the condition.  That process is often a checklist by proxy as in "I read this checklist in a magazine and you seem to have the symptoms.  You must have bipolar disorder."  In many ways that is like reading a manual about how to repair a complicated problem with your car.  Some untrained people may be able to pull that off, but the vast majority will fail.  The failure will occur at the level of pattern matching with the severe problems as well as the appropriate assessment of biases along the way.  That is not to say that experts are free of bias, but they are less susceptible to the common biases that occur along the way largely due to an accumulation of patterns that they have encountered over the course of their careers.

To develop the best possible understanding of psychiatric diagnosis and how it works might require consideration of some overlapping models of the conscious state in humans.  Consciousness is a complicated process concept, but it basically refers to the collection of mental processes that result in a stable personality and behavior over time.  An example of elements of consciousness is included in the representation below.  It contains descriptions that are found in the writings of David Chalmers and other authors on consciousness.  Chalmers breaks consciousness down into the easy problems or readily observable properties of consciousness and the hard problem.  The hard problem involves figuring out how the neurobiological substrate can generate conscious states and how those states are all unique.  There are a lot of theories about how that might happen, but none of them have been proven.


 The psychiatric assessment is trying to determine the parameters listed in the box at the right.  Some of the properties of consciousness are listed in the box at the left.  There is not a clear correlation between these elements, but what needs to be elicited in the interview will be determined to a large extent by the conscious state of the individual.  As an example, if I am interested in asking about sleep, I routinely take a sleep history that goes back to childhood.  I ask about insomnia, nightmares, night terrors, sleepwalking, and all of those states over the decades that gets me to the current age of my patient.  As an adult I ask about whether or not they have had polysomnography, whether they snore or have restless legs at night.  I ask them about the medical and non-medical treatment they have received for insomnia and if there were any complications.  I have to observe whether or not the person can reasonably respond to those questions or not and a lot of that depends on their conscious state.

In order to make a psychiatric diagnosis of a basic mood disorder, the primary criteria is that there has been a phasic mood disturbance for a certain duration.  In the case of depression the primary DSM-5 criteria is:  "Depressed mood most of the day, nearly every day, as indicated by subjective report or observation made by others" or  "Markedly diminished interest or pleasure in all, or almost all activities, most of the day, nearly every day."  That basic distinction taxes the conscious state of many people who are already diagnosed with mania or depression.  Wait a minute - "most of the day, nearly every day" - don't I have good days and bad days."  The number of people who make that observation when they are asked the specific question is significant.  When I hear that response, I remember the pre-DSM Feighner criteria for intermittent depression.  In those days it was acceptable to have good days and bad days.  Today in a complicated process occurring in the person's conscious state they need to decide if this phasic mood disturbance really applies or if there are other reasons for endorsing a positive response.  If they are handed a standard checklist for depression like the PHQ-9, the conscious thought process is much different than a psychiatrist asking them about an all encompassing mood disorder rather than "good days or bad days."

The process might even have to take a step farther back when the patient states:  "Wait a minute doc, I am not sure that I know what anxiety or depression really is.  Aren't they the same thing?  Doesn't one turn into the other? Can you explain it to me?"  This is a much different interview than a person coming in and declaring a problem.  This person is aware that some kind of problem exists.  They may have learned that from feedback from a spouse or an employer.  They don't know what to call it.  They might be aware of physical distress, but be unable to make the connection to emotional perturbations.  Is their concept of a disorder the same as the person who comes in declaring themselves to have the problem.  Probably not, but it is apparent to me from interviewing tens of  thousands of people over the past thirty years that everyone has a slightly different idea of the problem.  It is obvious that it is also a much different situation when the patient is handed a checklist of symptoms of depression and makes what is essentially a series of forced decisions about if they have depression and how severe it is.   Consciousness researchers have used the thought experiment about the color red for years.  That is, my experience of the color red, is probably different from your experience of the color red.  In other words, my conscious state processes the color red in a different and unique way compared with your conscious state.  Why would that not be true with regard to the various types of depression and anxiety?

 That brings me to another conceptualization that is often used to look at diagnoses like the dementias, schizophrenia, and attention deficit-hyperactivity disorder.  The abilities to plan, act, and perform these acts successfully is often referred to as executive function.  Although these functions tend to be arbitrary and arrived at by consensus, they have always been important in psychiatric diagnoses.   Major mood disorders, schizophrenia, and neurocognitive disorders may all have varying degrees of impairment in executive function.  Testing specific functions and trying to correlate them with behavior at the clinical level is frequently disappointing except in cases of significant brain damage.  By inspection, it is apparent that there is an overlap between executive functions and consciousness - but not a complete mapping by any means.  DSM-5 has a fairly extensive table on six Neurocognitive Domains (pages 593-595) that describes executive function as one of these domains.  Executive function is defined as planning, decision-making, working memory, inhibition, mental flexibility, and responding to feedback.  Clear examples of what can be observed in each case are given.  Neurocognitive disorders are clear problems in consciousness.



The common psychiatric approach to diagnosis and treatment is what I would call a biomedical approach.  It was elaborated on by George Engel in his famous paper on the biopsychosocial approach to medicine, but it was practiced extensively before that paper was written.  A lot of the social and familial aspects of this interview were undoubtedly influenced more by epidemiology and genetics rather than consciousness factors.  It has been known for some time that you make be more likely to have a heritable illness if it runs in your family or it occurs in members of your occupation.  But what does a psychiatrist also need to know about how anxiety develops.  Can it be transmitted directly from a parent who is a "worry wart" to a child?  Does the child recognize it at the time?  Do children remember when their father was enraged or their parents were fighting and they were wide awake listening to it all night long?  Do people remember what it was like to "walk on eggshells" due to all of this adversity occurring during their childhood?  Do all of these incidents affect elements of their conscious state that keep them stuck in what are defined as psychiatric disorders?  Without a doubt.

 Conscious states are important in both the diagnosis and treatment of psychiatric disorders, but for the purpose of this post I am ending on diagnostic considerations as noted in the first slide of this series.  I will briefly comment on the importance of each dimension.


Interview Context:  Psychiatrists are called on to provide services in a wide variety of environments.  The appropriateness of the environment for both assessment and treatment needs to be assured.  It is common for a third party to want to restrict access to the time of psychiatrists by rationing their time with the patient or total time allowed to see each patients.  Times vary greatly from system to system.  In some cases, a the time allocated for a new evaluation is 30 minutes and in others it can be up to 90 minutes.  I have completed complete interviews at both ends of the spectrum, but the limiting factor can never be some preconceived notion by an administrator.  The patient's conscious state is the limiting factor.  That includes how they respond to the psychiatrist and the introductory process of the interview.  It also depends on a quiet confidential environment and whether there are any observers in the room.  I have had many colleagues tell me that their interaction with patients is definitely affected both other people in the room.  This is a factor that can affect both the conscious state of the psychiatrist and the person being interviewed.

Empathy:  All psychiatric trainees learn a lot about empathy in early interviewing courses.  The necessary prelude to empathy is therapeutic neutrality.  That is a confusing term to nonpsychiatrists, but it essentially means not bringing in any extraneous interpersonal factors or emotions into the interview of a specific patient.  That ability is gained by self-analysis, experience, and in some cases personal psychoanalysis.  From the patient perspective, emotional reactions often surface as part of longstanding patterns of behavior.  They are often proximate to the problem at hand and very relevant in the initial interview situation.    

Empathy is taught as essentially a cognitive appreciation of the patient's emotional state.  The single best definition of empathy is from Sims in his book on descriptive psychopathology.   “In descriptive psychopathology the concept of empathy is a clinical instrument that needs to be used with skill to measure the other person’s internal subjective state using the observer’s own capacity for emotional and cognitive experience as a yardstick. Empathy is achieved by precise, insightful, persistent and knowledgeable questioning until the doctor is able to give an account of the patient’s subjective experience that the patient recognizes as his own.”  Sims captures the dynamic basis of the interview in this definition.  An empathic interview should result in a patient feeling very understood by the end.

Intellectual Capacity:  The intellectual capacity of the patient may vary considerably based on the psychiatric disorder they are experiencing.  By intellectual capacity, I am not referring to IQ scores.  I am referring to the ability of both the patient and the psychiatrist to recall and process information and consider a maximum number of explanations for what the patient is going through.

Emotional Capacity:  In the dyadic interview, the emotional capacity of both the psychiatrist and patient are important.  Can the patient describe the extent of any emotional disruption and the time course of that process.  Are they psychologically minded or can they appreciate social or psychological etiologies for these symptoms or do they view the problems as being treated only with a medication.  Psychiatrists are to a large degree self-selected on the basis of their interest in emotional problems. Many psychiatrists have had first hand experience in families where members have had a mental illness or addiction.  They had experience with all of the difficulties of getting that family member adequate treatment.  They recognize that these problems are very real and are generally highly motivated to provide treatment and advocacy.  As previously noted in the discussion of empathy, the ability to experience the emotional states of patients and describe them is necessary.  Sampling one's emotional state during the interview can also provide insights about the interview process, diagnosis, and overall meaning of the information being discussed.  As the average age of psychiatrists has increased, they have also seen thousands of patients with different kinds of emotional problems and successfully treated them.    

Information Content:  I find it surprising that the information content of diagnostic interviews is never estimated and the importance is never really taught.  There may be a correlation with the length of the interview, but not necessarily.  I can interview a person who gives brief high information content responses and do a reasonably good assessment in 30 to 45 minutes.  I can talk with a person who digresses and gives a lot of irrelevant details and still not have what I need at the end of 90 minutes or an hour.  The person who can assist me in doing the brief interview is not as common in my experience and I would say they represent 5% or 10% of the people I have seen.  There are also the Augenblick diagnoses or ones that can be made in the blink of an eye.  If I see a person with catatonia, delirium, or a stroke - I may not have to have them say anything to me.  Those rapid diagnoses will precipitate a thought process about what else needs to be ruled out and what tests need to be done immediately to confirm the diagnosis.  The information content in an interview is bidirectional and probably encompases severe channels including speech and paralinguistic communication.  The paralinguistic channel also contains information about the affiliative behavior of the participants.

Therapeutic Alliance:  An optimal diagnostic and treatment relationship flows from therapeutic alliance between psychiatrist and patient.  In other words - both are working together on a problem or set of problems that is bothering the patient.  It proceeds lie all patients interactions in medicine on an informed consent model.  Acute care psychiatry often involves the assessment and treatment of patients who are being detained on an involuntary basis because of safety concerns and in that situation the psychiatrist can be perceived as an agent of the state.  In that case and in many cases of long term treatment, it is often a good idea to review this principle with people in treatment to reorient them to the process.  Even a person who is being briefly seen for medication can have a problem in treatment if they perceive a psychiatrist a being poised over a prescription pad, ready to address their briefly stated problems with a new prescription.

Structure:  The psychiatrist has a responsibility to structure the interview so that the time is ultimately used to get results for the patient.  That means a singular focus on the patient, how the patient is proceeding in the interview, and how they are presenting the information.  That can mean giving additional information about the interview to the patient, providing necessary definitions, and doing whatever can be done to enhance the information content of the interview.  The introduction to the patient is critical because to this day there is still confusion over the definition of psychiatry.  I generally tell everyone my name, my years of experience, and present them with my business card.  After that I clear up any questions about psychiatry.  Some people ask about where I trained and I provide them with that information.  Some ask for clarification about the interview as we proceed.  A common question is: "Do you want the long version or the shirt version?"  Some early questions are also red flags and may be an indication of strong biases by the person being interviewed that may even preclude the interview itself.  Some of those decisions may also depend on the interview setting.  An example might be religion as a selection factor.  If a person tells me that they can only talk to a Christian using their specific definition and they want to ask me questions to determine my status, it might be easy to suggest that they see someone else in an outpatient setting, but a lot more difficult if you are the only available psychiatrist on an inpatient unit.

Technical Skill:  Like most professions, there is some variation in the interview and interpersonal skills of psychiatrists.  A psychiatric interview requires technical skills that psychiatrists have been focused on since early in their training.  Those skills are the focus of courses, seminars, books, papers and direct observation by training supervisors.  Since the oral board examinations have stopped, psychiatric residents now do the equivalent of oral board examinations on interview techniques during their training.  During an interview, a psychiatrist is listening for patterns and inconsistencies.  A psychiatric interview is not an interrogation.  In an interrogation, the interviewer generally has a bias and asks very leading questions to confirm that bias.  That style is evident in any number of police and crime television shows and films that are easily accessed these days.  In a psychiatric interview, the psychiatrist is developing hypotheses about diagnoses and formulations and inconsistencies with those hypotheses.  The interview itself can be very nonlinear and the psychiatric directs the interview from one major cluster of information to another.  A parallel process during the interview is recognizing the person's mental state and its potential origins.  Empathy as noted above is a critical aspect of that process.

Psychiatry is currently being practiced with an implicit rather than explicit focus on consciousness.  Making consciousness more explicit adds a lot to assessment and treatment.  The idea that every new patient being seen is truly a unique individual based on their conscious state is a primary organizing factor.  Their experience of mental distress is unique and can only be categorized with the broadest categories.  That emphasis creates a high bar for anyone who wants to be a good psychiatrist.  That psychiatrist by definition will critique each interview while they are documenting it and consider what was missed.  That psychiatrist will also critique any practice setting that requires them to interview patients according to electronic health record forms, diagnose people based on rating scales, or respond to patients in a stereotypical manner.  The recent emphasis on collaborative care is also a dead end in terms of consciousness.  The idea that a psychiatrist looking at rating scales and "managing populations" without ever talking to any of those patients is absurd from the standpoint of conscious states and diagnostic precision.

Human consciousness doesn't work that way and psychiatrists can't either.




George Dawson, MD, DLFAPA

Sunday, February 21, 2016

Testosterone Study Is Disappointing For More Than The Obvious Reasons

Testosterone

Testosterone replacement has been a controversial issue, despite a large number of physicians who prescribe it, FDA approval of products for mass marketing, and a number of advocates that see it as an anti-aging and performance enhancing drug for aging men.  The science behind is has been surprisingly slow.  In an era where inequities in health care are often argued by race or sex, this seems to be one where the science at least lags far behind what is known for women.  Expert opinion about testosterone replacement has changed very little over the years, despite much popular literature about how this has occurred for years in Europe and there is widespread benefit for physical and emotional well being of men as they age.  From a clinical perspective, psychiatrists are seeing more and more middle-aged men on testosterone replacement.  This treatment modality has significant implications for any medical treatment provided by psychiatrists as well as associated comorbidity.  From a psychiatric perspective it is also important to determine if the testosterone use is more than indicated, is associated with increasing muscle mass and body image changes, and if it occurring in the context of unreasonable expectations like preserving youth , reversing the effects of aging, or athletic performance enhancement.

In the most recent study of men 65 years of age and older the authors examined the effects of treatment with testosterone gel for a period of one year (1).  The total number of subjects was 790 out of a total of 51,085 men who were screened.  In order to qualify for the trial testosterone level had to be sufficiently low (less than 275 ng/dl) on one of two samples and that eliminated 85% of all of the screened men.  The trial was designed to look at physical function, sexual function, and vitality.  The treatment resulted in testosterone levels that were in the mid-normal range for 19 to 40 year old men.  Despite considerable medical comorbidity in the recruited patients there were clear cutoffs for medical comorbidity.  Those cutoffs included a history of prostate cancer or risk of prostate cancer on the Prostate Cancer Risk Calculator, other conditions known to cause hypogonadism, medications known to effect the concentration of testosterone, high cardiovascular and severe depression (PHQ-9 score >20).   The overall results showed that there was moderate benefit on sexual functioning and some benefit with mood and depressive symptoms but no effect on physical functioning or vitality.  A look at these measurements is instructive.

Physical Function was assessed using the 6 minute walk.  Recent normative data has been established for various age cohorts using subjects from several countries.   That data establishes normative curves for age cohort stratified by sex.  The six-minute walk distance (6MWD) ranged from 559 +/- 80 meters in 60-69 year old men to 514 +/- 71 meters in 70-80 year old men.  On two trials subjects usually walked on average 12 meter farther on the second trial.  In the present study, the criterion for a positive effects from testosterone was a walking distance increase of 50 meters.  When compared with controls, the testosterone treated men had significantly more men increasing the distance walked by 50 meters, the percentage of men exceeding this measure, the change from baseline, and the percentage of men with higher scores on the physical function domain test (PF-10) from the Medical Outcomes Study 36-Item Short Form Instrument (SF-36).  One of the concerns I had reading this methodology is the use of testosterone for physical performance enhancement.  Is it effective without using a training program?  Were the subjects in this study advised to extend their walking distances or speed?  Without it I am skeptical that it would have much of an effect.

Vitality was determined by measures on the FACIT-Fatigue score as the primary outcome measure.  Interestingly FACIT stands for Functional Assessment of Cancer Treatment and their web page links to an extensive list of modified rating scales.  I could not tell if the rating scale had been validated in normal 65 year old men without a cancer diagnosis.  No significant differences were noted between testosterone treated men and controls.  On secondary measures testosterone treated men were more likely to report higher energy at the end of the trial, but that measure was unspecified and may have been a line item in the SF-36.

Sexual Function was measured primarily by question 4 of the Psychosexual Daily Questionnaire.  This item is a 12 item yes-no checklist of male sexual behaviors, thoughts, and fantasies.  Greater testosterone levels achieved in treatment correlated with higher testosterone levels.  A secondary measure - the Derogatis Interview for Sexual Functioning in Men-II (DISF-M-II) also documented increased sexual desire and it was also used as a screen for participants in the Sexual Function arm of the trial.  The sexual function measures do appear to be more straightforward, but they are all self report measures over considerable time frames.

One of the most interesting aspects of this trial was an analysis of the side effects.  One of the main concerns in treating men with testosterone is the risk of prostate cancer that is sensitive to testosterone levels.   I have had personal communication with physicians who were treating patients with testosterone who developed widely metastatic prostate cancer.  The significant adverse effects in this trial were all summarized in a table.  There were 394 placebo treated men compared with 394 testosterone treated men.  The events were summarized according to prostate-specific antigen (PSA) level increases, diagnoses of prostate cancer, elevations of hemoglobin, myocardial infarction, stroke, all cause cardiovascular death, death and hospitalization.  Although there were a greater number of PSA elevations in the testosterone treated men, there was only 1 case of prostate cancer (compared to 0 in the controls) during the year of study and 2 cases of prostate cancer in the testosterone group and one in the placebo group in the subsequent year of the study.

The rationale for this study was try to to add to the results of previous trials that showed inconsistent results of testosterone replacement on muscle mass, body fat, sexual function, energy level, and physical function.  It is disappointing to read through all of these details and find out that there was not much of an effect and that the methodology in the 21st century is so weak.  The only good news that I can find in the article is that it is relatively safe to replace testosterone in 65 year old men who are rigorously screened for hypogonadism and prostate cancer risk.  Although selection bias for a project like this is certainly a consideration, I asked myself whether men self-selected for replacement by low testosterone ads would be rejected at the 85% level by their physicians.  Of course the researchers here point out that the risk over the long run can only be determined by larger trials or (my opinion) post marketing surveillance.  But post marketing surveillance as suggested by the FDA is really a blunt instrument compared with any type of organized pharmacosurveillance or screening all new cases of prostate cancer on a particular electronic health record for testosterone prescriptions. At some level,  I wonder if the research questions would have been answered more completely by trials focused solely on each groups, but there were a very large number of investigators.  Many of the investigators have the appearance of conflict of interest through affiliations with pharmaceutical companies and many do not.

The results of this study are consistent with what clinical psychiatrists see in their practice.  It is not uncommon to see men taking supraphysiological doses of testosterone and not wanting to reduce those doses.  It is common to see men on testosterone who stop taking it because there is no clear efficacy and/or because they are concerned that the women and girls in their life will accidentally come into contact with testosterone.  But let's face it - this is really not about hypoandrogenism.  That is not what is fueling the debate.  I am not an advocate of aging gracefully and accepting what happens.  I think if you have been dieting and exercising through the first 65 years of life it would be useful if medical science could provide something to help you maintain an active lifestyle and prevent the kind of morbidity that slows you down, leads to deconditioning and the host of metabolic factors that hasten aging and death.  Preventing that pathway of physical deterioration depends on maintaining attitude, muscle, joints, and bone.  This is another paper documenting that there is no clear solution to that array of problems.

It is unfortunate that medicine does not have a scientific solution at this point - even after hearing all of the unscientific hype about testosterone and growth hormone for the past 30 years.    

                  

George Dawson, MD, DLFAPA



References:

1:  Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS; Testosterone Trials Investigators. Effects of Testosterone Treatment in Older Men. N Engl J Med. 2016 Feb 18;374(7):611-24. doi: 10.1056/NEJMoa1506119. PubMed PMID: 26886521.

2:  Casanova C, Celli BR, Barria P, Casas A, Cote C, de Torres JP, Jardim J, LopezMV, Marin JM, Montes de Oca M, Pinto-Plata V, Aguirre-Jaime A; Six Minute Walk Distance Project (ALAT). The 6-min walk distance in healthy subjects: reference standards from seven countries. Eur Respir J. 2011 Jan;37(1):150-6. PubMed PMID: 20525717.

3:  Lee KK, Berman N, Alexander GM, Hull L, Swerdloff RS, Wang C. A simple self-report diary for assessing psychosexual function in hypogonadal men. J Androl. 2003 Sep-Oct;24(5):688-98. PubMed PMID: 12954659.


Brief Video:

The two minute NEJM video summarizing this trial can be found at this link.  Interestingly the video attributes sexual function, vitality, and physical function to testosterone decrease with age and yet full replacement to the point where it is equivalent to levels in much younger men does nothing for physical function or vitality.


Friday, February 19, 2016

NEJM and the Neurobiology of Addiction

From: Volkow ND et al. N Engl J Med 2016;374:363-371 - see attribution.


There are numerous articles in the popular press that attack the disease concept of addiction as well as many that attack the idea that addiction may be a biological based problem,  Volkow, Koob and McLellan have an interesting article in a recent edition of the New England Journal of Medicine that discusses both the neurobiology and some of the biases involved in stating that addiction is neither neurobiologically based or a neurobiologically based disease.  The article is relatively low in the details that reductionists like myself like to read but it is well referenced and a good overview of what is known about the neurobiology of addiction.  It is also a discussion of failed theories and what is currently known.  There is only one graphic and it is the basic one shown at the top of this post.  It shows a basic mapping of typical behaviors associated with addiction and is an elaboration of George Koob's previous all-encompassing one liner that sought to capture the behavioral pharmacology of addiction in one sentence:

"Addiction is a chronic relapsing syndrome that moves from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement."

In this review the authors describe three stages of addiction; binge and intoxication, withdrawal and negative affect, and preoccupation and anticipation.  They are located in the table immediately below the brain graphic in the above infographic.  They break it down at a neurobiological level.  For the binge and intoxication stage increased dopamine release at the reward centers occurs.  With repeated stimulation the dopamine release is attenuated in response to the reward and shifts to anticipation of the reward.  Most authors discuss the initial phase of this process as occurring on the ventral striatum, in dopaminergic neurons from the ventral tegmental area innervating the nucleus accumbens.  I had some initial difficulty seeing the nucleus accumbens but it is there.  The larger message  is that plastic or experience dependent changes occur in not only the nucleus accumbens but also the dorsal striatum, hippocampus, amygdala, and prefrontal cortex.  I also liked the authors' inclusion of the word salience defined as a property of the prefrontal cortex in assigning relative value to a stimulus.  It is common to attend addiction conferences and hear the term being bantered about without any clear reference to the prefrontal cortex attributing salience to a particular stimulus.

Their description of withdrawal and negative affect discusses how with repeated stimulation reward and motivational systems are focused on the more potent effects of addictive drugs rather than the usual correlates including food and fluids, social affiliation, sexual behavior, and even good decision making.  This used to be referred to as the Hijacked Brain Hypothesis which basically stated the same thing.  Any physician working in a large acute care hospital will see a significant number of patients admitted largely because they have been using intoxicants on a chronic basis and ignoring their basic need for food and fluids.  This behavior is consistent with a new set of priorities for the reward and motivational systems, that biases the system heavily in the direction of continued substance use.  The previous theory of increased sensitivity to dopamine and higher levels of dopamine in the dorsal and ventral striatum in persons with addiction was proven to be wrong.  In fact dopamine release is attenuated and the reward system becomes less sensitive to all activating stimuli.  This results in both the loss of drug-induced euphoria and the lack of reward effects for previous enjoyable and preferred activities.  Recovery of this effect takes a prolonged period of abstinence and a sustained effort to get back into previous activity patterns.  At the same time, the stress response mediated by corticotropin releasing factor and dynorphin are involved in further attenuation of reward system dopaminergic cells.  Combined with changes in the extended amygdala this results in a dysphoric state and decreased stress tolerance.  It is captured in the second part of Koob's sentence - addiction becomes "a compulsive disorder involving negative reinforcement."  At this point the person with an addiction is self administering a drug to "feel normal and function" rather than get high.

The preoccupation and  anticipation stage impaired dopaminergic and glutamatergic signalling in the prefrontal cortex inhibits more typical decision making and creates a bias in the direction of continued use.  Self monitoring processes that evaluate the decision, whether or not it was successful and whether or not it was adaptive are similarly affected by these systems.  The value of the reward is depicted in the graphic below from Fuster's text The Prefrontal Cortex:



           

 The authors clarify their use of the term addiction relative to the more commonly used DSM-5 terms. With the advent of DSM-5 the familiar definitions of use and abuse disappeared and there is a single use category.  Severe use disorder requires 6 or more of the 11 symptoms of the use disorder.  The authors equate severe use disorder with their use of the term addiction.  Thinking about the demographics of people with one or more severe use disorders fits their description of addiction.  It is also much more likely that this group of patients will have markers and behaviors that cannot be dismissed by those who criticize a neurobiological approach to addiction.

Apart from the neurobiology update, the other interesting aspect of this paper was the authors taking on critics of a neurobiological model of addiction.  They are generally the same crowd who is critical of the disease model of addiction.  This paper defines a more specific model of addiction and its features than the disease model, even though popular surveys illustrate that most people see addiction alcoholism, and severe psychiatric illnesses as diseases.  At some level the popular and medical definitions of disease encompass a diverse group of conditions and arbitrary definitions can be adopted to support and argument.  A favorite is always that there is no known observable lesion or pathology in conditions that are not diseases.  I have examined several of these arguments about addiction in a previous post.  The authors here include their examination of 7 arguments entitled:  Criticisms of the Brain Disease Model of Addiction and Counter‐ Arguments.  The only substantial way their differ from my examination of the criticisms of addiction being modulated by a distinct set of pathological neurobiological features is that they include two points about public policy specifically how research is funded and how patients have benefitted.  One of the most common misconceptions about psychiatric illness and addictions when they are approached from a neurobiological perspective is that critics seem to think that this is tantamount to the "medicalization" of a problem and that this means only a medical intervention or medication can be used to treat the disorder.  In the field of addiction, excellent work has been done showing a number of unique paths to recovery that may depend on speculative neurobiological mechanisms, but do not depend on the use of medications or contact with physicians.  Critics of neurobiology seem to see the brain as a turf war rather than a need for a deeper understanding of the most intricate organ in the body.

I encourage a careful reading of this paper, by anyone who wants a brief overview of how addiction may affect the brain.  This is not a comprehensive review by any means and at some point I will come back and point out some of the shortcomings.  If you are a psychiatrist or psychiatric resident - you need to know what is in this paper at the minimum.  That is true if you are involved in the diagnosis and treatment of addiction or not.  The systems discussed in this paper are involved in cognition and complex decision making.  Contrary to popular belief there are no decisions made that are devoid of an emotional component.  That fact does not come alive until you know the relationship between limbic structures and reward/motivational systems.  Thirty years ago, some of the free literature from pharmaceutical companies contained graphics highlighting some of these systems and how they may be affected in schizophrenia and psychosis.  In the intervening time period, the bulk of useful research in the area came from scientists and physicians doing research in addiction.

As the knowledge in this area increases, this neurobiology will have wider applicability across the entire spectrum of psychiatric disorders.  


George Dawson, MD, DLFAPA



References:

1: Volkow ND, Koob GF, McLellan AT. Neurobiologic Advances from the Brain DiseaseModel of Addiction. N Engl J Med. 2016 Jan 28;374(4):363-71. doi: 10.1056/NEJMra1511480. PubMed PMID: 26816013.


Attribution:

Graphic at the top is from reference 1, with permission from the Massachusetts Medical Society.  License date is Feb 01, 2016 - license number is 3801731329358 for 12 months from the date of the license.  According to the publisher I am classified as a free-lancer (not-for-profit publisher) and hence the change in my LinkedIn status to free-lance writer at Real Psychiatry.


Sunday, February 14, 2016

A Real Case Of Psychosis And What Can Happen




Public radio continues to be a rich source of information when it comes to real life psychiatric problems.  In this case the NY Times was also involved.  Considering the date the story was filed the usual critics have not chimed in yet.  They may not be able to since no psychiatrist or psychiatric medication was involved in the care of this patient - and it shows.  There is no more compelling story that psychiatric disorders exist, are severe, and for various reasons can end catastrophically.  I won't  belabor the point that I have treated hundreds of people with very similar problems.  For 22 years, I treated people with severe psychiatric disorders and most of them had psychotic disorders.  The episode of psychosis described in this story is the kind of psychosis that psychiatrists treat, not the vague symptoms described in a recent paper that suggested that some symptoms of psychosis are a normal experience.

Before I get into a brief discussion of the scenario, I would like to acknowledge the patient Alan Pean for sharing his story.  I heard his story on This American Life and the host Ira Glass was explicit that Mr. Pean  had signed a release of information so that the hospital records and a 50 page report of the incident could be used to construct what had happened. His family members were also available for the interview.  In this age where health care companies view patient information as proprietary corporate information I applaud Mr. Pean's decision to make this very personal private information public.   There are numerous lessons to be learned from this incident that I hope to make explicit  at the end of this post.

For anyone interested in listening to the audio version of this story go to the This American Life web site and look up episode 579 My Damn Mind.  This amazing story begins after Mr. Pean has been shot in the chest and is bleeding to death on the floor of his hospital room.  There is blood  everywhere on the floor and people entering the room have to put on shoe covers.  Later in the story we learn that he lost about 1/3 of his total blood volume.  A trauma surgeon is demanding that the police take the handcuffs of Mr. Pean because even though he is shot and immobile, he is handcuffed lying on the floor.  According to the Centers For Medicaid and Medicare (CMS) report he was trying to get up after he was shot and saying that he was "Superman". From there,  Ira Glass starts to interview Mr.  Pean about the 20 hours prior to this incident.  He describes being anxious and at times panicky.  He was sleeping 4 hours per night and recognized he was manic from his past experiences in 2008 and 2009.  He was diagnosed with possible bipolar disorder treated with medication and had no further episodes in 6 years.  He was trying to unwind by playing a video game online with his friends.  He started to think that the video game controller had been reprogrammed by the enemy and was switching on a processor inside of him.  He could not logon to the game because he knew that drones would triangulate on him if he did and destroy his apartment.  He called his brother for advice.  His brother told him to lay down and put cold water on his face.  He concluded that his circuits were overheating like a robot and his brother knew this.  At one point he knew he had to escape from his third floor apartment balcony because snipers were closing in on him.   As he looked down he thought remember your training - you are trained for this.  At that point Ira Glass jokes with him about that point and they both laugh.  He of course had no training and it was apparent to me that Glass had not talked with many delusional people.  Pean executes a perfect drop to the second floor balcony and grabs the railing.  From there he notices two air conditioning units on the ground swings past then and jumps.  He hits the ground running for his car because he has called in a drone strike in his apartment building using Google Maps.  He jumps in his car and heads out of the parking lot.  When the gate doesn't open he rams it until it opens.  At this point he is thinking that his rendezvous point is the hospital.  In a moment of clarity he also realizes that he needs Geodon, the medication that he takes for psychosis.  He feels like he is a bionic person or a cyborg driving the car at a high rate of speed toward the hospital.  As he approaches, he loses control and hits several autos and the hospital building totaling out his car.  An EMT sees the crash. puts him on a gurney and wheels him into the Emergency Department.

This entire sequence of events was driven by delusions.  In the narrative Pean described an intense fear for his life and the fact that his "adrenaline was pumping" at times.  That combination of emotion, especially high anxiety and delusional thinking can lead to impulsive behavior and a lack of typically rational decision-making.  It is an example of "dangerousness" or the emergency criteria that governs whether a patient with psychiatric problems is offered inpatient treatment or not.  The problem is that Pean's actions are all internally consistent with his delusional state.  He talks with his brother on the phone and does not mention that he thinks he is delusional.  In this state of mind, it is very likely that anyone assessing him for "dangerousness" would seriously underestimate what he was capable of.  A lot of his acts are also environmentally determined.  His delusional biases interpret the information as he sees it.  When he was speeding toward the hospital, he was convinced that some of the buildings he was passing were going to explode at any minute.  Despite the non-psychiatric interview, I think the emotion driving the delusionally based decisions is apparent.  Ira Glass points out that the narrative though irrational is internally consistent like a movie and not what he expected.

Pean is eventually admitted to the trauma surgery service for further observation of injuries from the car crash.  There was ample information that he had a significant psychiatric disorder including direct statements from his father who is a physician.  He is noted to be disoriented and believes that it is 1989.  His speech at time is incoherent, but the staff observe him to be lucid at times.  Immediately prior to the incident, several staff report the patient coming out of his room into the hallway either nude or partially clothed.  He had to be redirected back into his room and asked to put a gown back on.  He was dancing and in some cases danced away from staff trying to help him into the gown.  With his history (and assuming that brain trauma has been ruled out) these can all be features of a severe psychosis.  His parents are concerned that they plan to discharge him without psychiatric consultation.  The hospital they are in does not have an acute inpatient psychiatric unit and he has not seen a psychiatric consultant.  They leave at some point to rent a car so that they can drive him to psychiatric facility if necessary.  While they are gone he becomes extremely agitated.  He is tasered several times and ultimately shot in the chest just 40 minutes later.

The New York Times article goes into detail about the issue of armed security in hospitals.  It reviews the number of people with mental illness who were shot or tasered and killed.  I have pointed out some of the problems with firearms in psychiatric hospitals in an article about visitors carrying firearms into Texas state psychiatric hospitals.  The same issues apply in this case.  Firearms are not a deterrent when confronting a person who is agitated and psychotic.  In this case the patient recalls that he was some kind of cyborg secret agent.  In that frame of mind he is likely to interpret any efforts to contain his agitation and aggression as potentially dangerous to him and it would provoke extreme behaviors to counter that aggression.  In every security setting where I have worked, security and law enforcement lock up their weapons and do not take them into patient care areas even if a patient is highly aggressive and out of control.  It takes well trained staff and security to be able to do this and recognize why this is the best approach.  It also involves a contingency plan to physically restrain the patient in a safe manner as quickly as possible if the patient does not respond to verbal deescalation.

The CMS document discloses several important pieces of information that are not in the media.  The first eye opener is that the hospital administration said the security officer was justified in shooting the patient because he had assaulted them.  That statement grates on any inpatient psychiatrist or nurse who recognizes that is not the appropriate frame of reference for this incident.  This is not a street fight.  This is a vulnerable patient in a hospital whose rights and standard of care needs to be recognized.  One of the implicit assumptions in most hospitals is that psychiatrists and psychiatric staff are supposed to view aggression as an occupational hazard.  A unidentified staff member speaks to that in the radio piece and is very explicit about the amount of aggressive behavior that he sees in the hospital and the fact that he gets hit.  That is not the case in other parts of the hospital where aggressive behavior is more frequently seen as criminal behavior.  Early statements from the hospital administration suggested that the law enforcement officers here were justified in shooting Alan Pean, but they were subsequently modifying their position.  He was also charged with 2 counts of aggravated assault on both of the law enforcement officers who entered his room.  Clearly this is a psychiatric problem and the patient needs  protection.  As I read through the 50 page document from CMS, the suggested solution varied from being vague to solutions that many hospitals already have such and an emergency response team for behavioral emergencies.  They suggest that armed law enforcement officers should be only in the ED, not be involved in the behavioral emergencies until all other resources have been exhausted and intervene only in the case of life-threatening or criminal activity.

One of the primary conclusions of the This American Life piece is that is could have been prevented if the patient had received a psychiatric evaluation.  A hospital staff person pointed out that this was standard procedure and also that any number of staff used to encountering aggressive patients could have contained the patient without firearms.  There is apparently an inpatient psychiatric unit at this medical center where he could have been transferred.  Alan Pean responds to Ira Glass's question about how it is that he went to the hospital with mania and psychosis and ended up getting shot in the hospital instead.  One of his conclusions is that he is a young black man and he does not think that it would happen if he was white.  He remains understandably traumatized by his near death experience.

The only logical conclusion here is one that I have already reached many times in many posts on this blog.  Violence and aggression are treatable problems when they are associated with psychiatric illnesses.  There needs to be psychiatric and psychiatric nursing expertise in major hospitals at several levels.  One of the unusual parts of this story was all of the information available suggesting that the patient in this case had a significant mental illness.  That was made even clearer when his physician father made the statement, requested the psychiatric evaluation, and was told that the patient was being discharged instead.  The CMS report does not address staffing levels in the hospital and whether there are adequate staff to address the problem.  In my experience, a nurse and another staff person going to address a situation where there is potential aggression by a young manic patient is not enough staff.  I have personally found myself in many situations when I walked in a room and there were four highly trained nursing assistants out in the hallway, ready to intervene if necessary.  In every case our goal was to protect the patient from injury.

The lesson in this case is that if you go to a hospital with aggressive behavior due to a psychiatric disorder somebody on the receiving end needs to know what to do to keep you safe.  Only a fraction of American hospitals are set up to do this and provide the necessary psychiatric care to resolve the crisis.  Some hospitals will never be equipped to deal with this problem and the practical solution in most communities is to triage violent and aggressive people to more appropriate facilities.  Even though the New York Times article points out that there has been a 40% increase in hospital violence, many of the people with that problem never make it there.  There needs to be enough capacity to treat people so that people with violent and aggressive behavior from a psychiatric illness can go to a hospital knowing that their problem will be diagnosed and treated and that their safety will be assured.  
             
Nobody should ever have to experience what Alan Pean went through.



George Dawson, MD, DLFAPA




References:

1:  This American Life.  579: My Damn Mind.  February 12, 2016.

2:  Elisabeth Rosenthal.  When The Hospital Fired The bullet.  New York Times February 12, 2016.

3:  Department of Health and Human Services Centers for Medicare and Medicaid Services.  Statement of Deficiencies and Plan of Correction.  St. Joseph Medical Center; 1401 St. Joseph Parkway, Houston Texas 77002.


Supplementary 1:

In the report by This American Life, it was apparent that at least some authorities were looking for evidence that the patient had aggressive tendencies outside of the episodes of mania and psychosis.  They did this by asking his family if he had any criminal convictions.  In the original hospitalization he was also noted to have THC in his toxicology.  The fact that there were no other drugs present and that THC can persist a long time was emphasized in the This American Life piece.  In fact, THC is not a trivial compound in this case.  No conclusions can be made based on the existing data and the lack of direct assessment of this patient, but this compound should be avoided by anyone diagnosed with bipolar disorder, especially if there is any doubt about the diagnosis.


Twitter Graphic:
















Sunday, February 7, 2016

Anecdotes Are Not Evidence And Other "Evidence-Based" Fairy Tales



A lot depends on the kind of anecdote that you are talking about.  When we talk about anecdotes in medicine that generally means a case or a series of cases.  In the era of "evidence based medicine" this is considered to be weak or non-existent evidence.  Even 30 years ago when I was rounding with a group of medicine or surgery residents: "That's anecdotal..." became a popular part of roundsmanship as a way to put down someone basing their opinion on a case or series of cases.  At the time, series of cases were still acceptable for publications in many mainstream medical journals.  Since then there has been and inexorable march toward evidence-based medicine and that evidence is invariably clinical trials or meta-analyses of clinical trials.  In some cases the meta-analyses can be interpreted in a number of ways including interpretations that are opposed to the interpretation of the author.  It is easy to do if a biologically heterogeneous condition is being studied.

There has been some literature supporting the anecdotal but it is fairly thin.   Aronson and Hauben considered the issue of drug safety.  They made the point that isolated adverse drug reactions are rarely studied at a larger epidemiological level following the initial observation.  They argued that they could establish criteria for a definitive adverse event based on a single observation.  In the case of the adverse drug event they said the following criteria could be considered "definitive":  extracellular or intracellular deposition of the drug, a specific anatomic location or pattern of injury, physiological dysfunction or direct tissue damage, or infection as a result of an infective agent due to contamination (1).  They provide specific examples using drugs and conclude: "anecdotes can, under the right circumstances, be of high quality and can serve as powerful evidence.  In some cases other evidence may be more useful than a randomized clinical trial.  And combining randomized trials with observational studies, or with observational studies and case series, can sometimes yield information that is not in clinical trials alone."  This is essentially the basis for post marketing surveillance by the Food and Drug Administration (FDA).  In that case, monitoring adverse events on a population wide basis, increases the likelihood of finding rare but serious adverse events compared with the the original trial.

Enkin and Jadad had a paper that also considered anecdotal evidence as opposed to formal research (2).   They briefly review the value of informal observation and the associated heuristics, but also point out that these same observations and heuristics can lead some people to adhere to irrational beliefs.  The values of formal research is a check on this process when patterns emerge at a larger scale.  Several experts have applied Bayesian analysis to single case results, to illustrate how pre-existing data can be applied to single cases analyses with a high degree of success.  Pauker and Kopelman (3) looked at a case of hypertension and when to consider a search for secondary causes - in this case pheochromocytoma.  They made the interesting observation that:

"Because the probability of pheochromocytoma in a patient with poorly controlled hypertension who
does not have weight loss, paroxysms of sweating, or palpitations is not precisely known, the clinician often makes an intuitive estimate.  But the heuristics (rules of thumb) we use to judge the likelihood of diseases such as pheochromocytoma may well produce a substantial overestimate, because of the salient features of the tumor, its therapeutic importance, and the intellectual attraction of making the diagnosis."   

They take the reader through a complex presentation of hypertension and likelihood ratios used to analyze it and conclude:

"Hoofbeats usually signal the presence of horses, but the judicious application of Bayes' rule can help prevent clinicians from being trampled by a stampeding herd that occasionally includes a zebra."

In other words, by using Bayes rule,  you won't subject patients with common conditions to excessive (and risky) testing in order to not miss an uncommon condition and you won't miss the uncommon condition.  Looking at the data that supports or refutes that condition will make it clear, if you have an idea about the larger probabilities.

How does all of this apply to psychiatry?  Consider a few vignettes:

Case 1:  A psychiatric consultant is asked to assess a patient by a medicine team.  The patient is a 42 year old man who just underwent cardiac angiography.  The angiogram was negative for coronary artery disease and no intervention was necessary.  Shortly afterwards the patient becomes acutely agitated and the intern notices that bipolar disorder is listed in the electronic health record.  He calls the consultant and suggests an urgent consult and possible transfer to psychiatry for treatment of an acute manic episode.  The consultant arrives to find a man sitting up in bed, appearing very angry and tearful and shaking his head from side to side.

Case 2:  A 62 year old woman is seen in an outpatient clinic for treatment resistant depression.  She has been depressed for 20 years and had had a significant number of medication changes before being referred to a psychiatric clinic.  All of the medications were prescribed by her primary care physician.  She gives the history that she gets an annual physical exam done each year and they have all been negative.  Except for fatigue and some lightheadedness, her review of systems is all negative.  She is taking lisinopril for hypertension, but has no history of cardiac disease.  She has had electrocardiograms (ECGs) in the past but no other cardiac testing.  The psychiatrist discusses the possibility of a tricyclic antidepressant.

Case 3:  An inpatient psychiatrist has just admitted a 46 year old woman who is concerned about the FBI.  She has been working and functioning at a high level until about a month ago when she started to notice red automobiles coming past her cul de sac at a regular frequency.  She remembered getting into an argument at work about American military interventions in the Middle East.  She made it very clear that she did not support this policy.  She started to make the connection between the red automobiles and the argument at work.  She concluded that an employee must have "turned her in" to the federal authorities.  These vehicles were probably the FBI or Homeland Security.  She noticed clicking noises on her iPhone and knew it had been cloned.  She stopped going into work and sat in the dark with the lights out.  She reasoned it would be easier to spot somebody breaking into her home by the trail of light they would leave.   There is absolutely no evidence of a mood disorder, substance use disorder, or family history of psychiatric problems.  She agrees to testing and all brain imaging and laboratory studies are normal.  She agrees to a trial of low dose antipsychotic medication, but does not tolerate 3 different medications at low doses.

These are just a very few examples of the types of clinical problems that psychiatrists encounter on a daily basis that require some level of analysis and intervention.  A psychiatrist over the course of a career is encountering 20 or 30 of these scenarios a day and ends up making tens of thousands of these decisions.  What is the "evidence basis" of these decisions?  There really is nothing beyond anecdotes with the availability of various strengths of confirmation.  What kinds of evidence would the evidence based crowd like to see?  In Case 1, a study that looked at behavioral disturbances after cardiac catheterization would be necessary, although Bayes would suggest the likelihood of that occurring would be very low.  In Case 2, a large trial of treatment approaches to 62 year old women with depression and fatigue would be useful.  I suppose another trial of what kinds of laboratory testing might be necessary although much of the literature suggests that fatigue is very nonspecific.  In most cases where patients are being seen in primary care - fatigue and depression are indistinguishable.  Extensive testing, even for newer inflammatory markers yields very little.  Further on the negative side,  evidence-based authorities suggest that a routine physical examination and screening tests really adds nothing to disease prevention or long term well being.  Case 3 is more interesting.  Here we have a case of paranoid psychosis that cannot be treated due to the patient experiencing intolerable side effects to the usual medication.  Every practicing psychiatrist knows that a significant number of people can't take entire classes of medications.  Here we clearly need a clinical trial of 40 year old women with paranoid psychoses who could not tolerate low dose antipsychotic medication.

By now my point should be obvious.  None of the suggested trials exist and they never will.  It is very difficult to match specific patients and their problems to clinical trials.  Some of the clinical occurrences are so rare (agitation after angiography for example) that it is very doubtful that enough subjects could be recruited and enrolled in a timely manner.  And there is the expense.  There are very few sources that would fund such a study and these days, very few practice environments or clinical researchers that would be interested in the work.  Practice environments these days are practically all managed care environments where physician employees spend much of their time administrative work, the company views clinical data as proprietary, and research is frequently focused on advertising and marketing rather than answering useful clinical questions.

That brings us to the larger story of what the "evidence" is?  The anecdotes that everyone seems to complain about are really the foundation of clinical methods.  Training in medicine is required to experience these anecdotes as patterns to be recognized and classified for future work.  They are much more than defective heuristics.  How does that work?  Consider case #1.  The psychiatric consultant in this case sees an agitated and tearful man who appears to be in distress.  The medicine team sees a diagnosis of bipolar disorder and concludes the patient is having an acute episode of mood disturbance.  The consultant quickly determines the fact that the changes are acute and rejects the medical team's hypothesis that this is acute mania.  After about 5 questions he realizes that the patient is unable to answer, pulls a pen out of his pocket, and asks the patient to name of the pen.  When he is not able to do this, he performs a neurological exam and determines the patient has right arm weakness and hyperreflexia.  An MRI scan confirms the area of an embolic stroke and the patient is transferred to neurology rather than psychiatry.  The entire diagnostic process is based on the past anecdotal experience of diagnosing and treating neurological patients as a medical student, intern, and throughout his career.  Not to labor the point (too much) - it is not based on a clinical trial or a Cochrane review.                

The idea that the practice of medicine comes down to a collection of clinical trials that that are broken down according to a proprietary boilerplate and generally conclude that the quality of most studies is low and therefore there is not much to draw conclusions on is absurd.  Trusting meta-analyses for answers is equally problematic.  You might hope for some prior probability estimates for Bayesian analysis.  But you will find very little in the endless debate (4) about whether or not antidepressants work or they are dangerous.  You will find nothing when these studies are in the hands of journalists who are not schooled in how to practice medicine and know nothing about treating biologically heterogeneous populations and unique individuals.  No matter how many times the evidence based crowd tells you that you are treating the herd - a physician knows that if they treat the herd - it is one person at a time.  They also know that screening the herd can lead to more problems than solutions.

Treating the herd would not allow you to make a diagnosis of complete heart block and immediate referral to Cardiology for pacemaker placement (Case 2) or psychotherapy with no medications at all and eventual recovery (Case 3).  If you accept the results of many clinical trials or their interpretation by journalists - you might conclude that your chances of recovery from a complex disorder are not better than chance.  There is nothing further from the truth.

That is why most of us practice medicine.



George Dawson, MD, DLFAPA


References:

1:   Aronson JK, Hauben M. Anecdotes that provide definitive evidence. BMJ. 2006 Dec 16;333(7581):1267-9. Review. PubMed PMID: 17170419; PubMed Central PMCID: PMC1702478.

2:  Enkin MW, Jadad AR. Using anecdotal information in evidence-based health care:  heresy or necessity? Ann Oncol. 1998 Sep;9(9):963-6. Review. PubMed PMID: 9818068.

3:  Pauker SG, Kopelman RI. Interpreting hoofbeats: can Bayes help clear the haze? N Engl J Med. 1992 Oct 1;327(14):1009-13. PubMed PMID: 1298225.

4:  Scott Alexander.  SSRIS: MUCH MORE THAN YOU WANTED TO KNOW.  Slate Star Codex posted on July 7, 2014.



Attribution:

Photo at the top is Copyright Gudkov Andrey and downloaded from Shutterstock per their Standard License Agreement on 2/3/2016.