The Recent Takedowns of Adult ADHD

 

Psychiatry seems doomed to argue endlessly about whether certain conditions exist or not and whether they can be characterized by written criteria. The latter condition is the most easily dismissed since clinical training is necessary to recognize conditions. You cannot just sit in an office, read the DSM and call yourself a psychiatrist. Whether conditions exist or not is more debatable but often slides into rhetoric that suggests inadequate training, ignorance, and/or significant conflict of influence or undue influence by the pharmaceutical industry. Consideration of the undue influence can easily be applied at the global level since Pharma has massive marketing efforts, direct to consumer advertising in the US, and at least one major political party pulling for them.

That brings me to the recent commentaries about adult ADHD (1, 2). The first reference (1) doubts that adult ADHD exists for the most part and sees the diagnosis primarily as the result of a marketing scheme by Eli Lilly for atomoxetine and ignoring affective temperaments and other states that may affect attention. Atomoxetine was invented as a norepinephrine reuptake inhibiting antidepressant and like other members of this class of drugs – it did not work for depression. Since it is not technically a stimulant it was tested for ADHD and found to be effective. It is unique relative to other ADHD medications and not surprisingly it was heavily marketed while on patent. The patent expired on May 2017. The years on the market patent protected were 2002-2017. The first references to the diagnosis of adult ADHD were noted in the 1980s. Reference 2 suggests that the diagnosis of ADHD in children in the US is around 2-3% with adult numbers half that based on the work of one author.  Contrasting numbers of a lifetime prevalence in adults as 8.1% and surveys estimating current prevalence at 4.4% are described as “absurdly high” but qualified on methodology (surveys vs interviews).  Some authors have the opinion that books published about adult ADHD like Ratey and Hollowell's  Driven to Distraction were a major source of public interest in the diagnosis and instrumental in getting it into the public vernacular. 

Before I get started – let me say that the only stake I have in this argument is making sure that the complexity of the situation is adequately described. Practically all the pro/con arguments in psychiatry are gross oversimplifications and based on what I know about the literature – I had no reason to expect that this was any different.  I am already on record on this blog describing how to diagnose and treat ADHD and not fall into the common problems of misdiagnosis, prescribing to people with substance use problems, or prescribing to people who view these medications as performance enhancers. I have successfully treated adult ADHD with both on and off label medications and can attest to the fact that it is a valid and treatable diagnosis.

Let me start out by looking at the prevalence estimates. These figures are very popular in the press to indict diagnosticians in the United States compared with some European countries and sell more papers. The problem with prevalence estimate is that the range can vary significantly due to methodological differences in the surveys. That question was looked at (3) and the title of that paper asked if ADHD was “an American condition”.  The authors reviewed 22 studies based on DSM-III criteria and 19 studies based on DSM-IV criteria.  Twenty prevalence estimates were done on the US and 30 were done in other countries.  They demonstrated that the range of prevalence across all studies was approximately the same and that ADHD was not just an American condition. Since then numerous prevalence studies have been done in other countries – more recently using DSM-5 criteria showing similar ranges.

On the issue of adult ADHD, a recent review looked at the issue adult ADHD and symptomatic adult ADHD prevalence by the 6 WHO regions (4).  Their overall goal was to determine the worldwide prevalence of adult ADHD. They looked at the issue of persistent or childhood onset ADHD and symptomatic adult ADHD with no evidence of childhood onset and estimated the prevalence of those two groups separately.  The pooled prevalence of persistent adult ADHD was 4.6% and for symptomatic ADHD it was 8.83%.  These authors also looked at prevalence by a list of demographic factors, diagnostic criteria, addition to geographic areas as well as the decreasing prevalence by age groups.   

 

Study	Target Population	Prevalence % (US vs Non-US) ranges or pooled
Faraone, et al (2002)	DSM-III ADHD DSM-III-R ADHD DSM-IV	(9.1-12.1) vs. (5.8-11.2) (7.1-12.8) vs. (3.9-10.9) (11.4-16.1) vs. (2.4-19.8)
Polanczyk, et al (2007)	Pooled prevalence estimates of ADHD by geographic location.  N= number of studies in each WHO designated location	North American (N=32)  6% Europe (N=32)  4.5% Oceana (N=6) 4.5% South American (N=9) 12% Asia (N=15) 4% Africa (N=4) 8% Middle East (N=4) 2.5%
Song, et al (2021)	Pooled estimates and ranges of Adult ADHD worldwide by WHO designated geographic areas	North America (N=3) 6.06% Europe (N=10) 7.12% Oceana (N=4) 9.67% South America (N=3) 6.06% Asia (N=1) 25.6% Africa (N=1) 9.17% Middle East (N=2) 16.58%

 

This study raises the issue of whether ADHD can be acquired rather than be a childhood onset illness. The reality is that there are many paths to acquired attentional deficit that have been treated over the course of my 35 years in the field.  The best examples are neurodegenerative diseases, strokes, and brain injuries. Neuropsychiatrists have written about treating the associated cognitive, mood, and motivational deficits with stimulants.  But a more relevant question is whether mechanisms exist that can result in people with none of these acquired brain injuries.  The answer comes from modern genetics. Polygenic risk scores (of all diseases) suggest that there are high risk individuals who show no evidence of an illness as adults. These examples of incomplete penetrance are usually explained as environmental factors, additional genetic dynamics such as aging or protective factors. I see no reason why these factors could not occur in an ADHD genotype after childhood. The other significant genetic factor is spontaneous mutation or as a recent commentator put it: “You don’t die with the genome you were born with.” Psychiatry has focused on familial studies for the past 50 years, but it is likely that significant numbers of most conditions occur as the result of spontaneous mutations rather than strictly hereditary transmission. That is borne out in clinical practice every day.

The authors (1) make the argument that ADHD is not a “scientifically valid” diagnosis. They explain “these symptoms have not been shown to be the result of a scientifically valid disease (adult ADHD) and better explained by more classic and scientifically validated psychiatric conditions, namely diseases or abnormalities of mood, anxiety, or mood temperament.”  Mood temperament is a stretch.  It is rarely commented on in adult psychiatry and then in extreme cases.  It is not contained in the DSM. Part of the reason is selection bias.  Psychiatrists are seeing people who have failed multiple other treatments and I have referred to this as being the treatment provider of last resort. 

Another factor is that ADHD is a quantitative rather than qualitative disorder – that is the cognitive symptoms are at the extreme end of normalcy and it is difficult to draw a line to demarcate illness from normal in many cases. A comparable example from medicine is hypertension.  The cutoff for what is considered hypertension has varied significantly over the decades (9, 10) and even now considers antihypertensive side effects as a qualifier for treatment.  That means that for any 2 people with the same marginally elevated blood pressure only one might get consistently treated. At one point hypertension was considered by some physicians to be a necessary compensatory mechanism that should not be treated (10). On the issue of quantitative aspects of psychiatric disorders in general – dimensional approaches are often suggested as a solution and the question is whether they work any better than the impairment criteria used in the DSM.  That is especially true in a clinical setting where a patient is presenting with a clear problem that they are asking for help with

On the issue of validity, studies have been done demonstrating reliability and validity (8) on both the DSM criteria as well as various rating scales for adult ADHD that are consistent with the diagnosis. There have also been detailed discussions of how to approach the problem clinically (11).  Those discussions include how to differentiate mood disorders from ADHD and how to approach the functional impairment criteria in the clinical interview.

That brings me to the issue of temperaments mentioned in reference 1.  Temperaments have been researched in various contexts in psychiatry over the past decades.  Most psychiatrists of my generation first heard about them on child psychiatry rotations and the work of Stella and Chess. In adults, temperaments are more descriptions of hyperthymia, cyclothymia, and dysthymia and are generally considered in the differential diagnosis of subclinical mood disorders.  The best example is hyperthymia and it has been referred to both as a temperament and a personality. Hyperthymic people are generally high energy, require less sleep, and are social, talkative, and outgoing. They may be very productive and have increased libido relative to their peers. In clinical interviews they may say that their friends think they are “bipolar” and need to be treated. But careful interviewing demonstrates that they lack the symptom severity and degree of impairment necessary for a diagnosis of bipolar disorder.  Ideally the initial interview results in that formulation and the psychiatrist can advise the person about why treatment is not necessary.

Reference 12 looks at the issue of temperaments in a retrospective controlled study of patients being treated with stimulants who were referred to a mood disorders clinic.  The authors acknowledge the selection bias in their study design. I can not think of a better design to pick up misdiagnosed patients than this one. To cite one example – of the 87 amphetamine treated referrals only 50% had a past diagnosis of ADHD. The authors acknowledge that there is no standard way to determine affective temperaments and decide to use the TEMPS-A with a cutoff of 75% of the items. If you are able to find a copy of the TEMPS-A (it is not easy) – you will find a list of 50 true-false questions like “I’m usually in an upbeat or cheery mood.” The questions are reminiscent of the Minnesota Multiphasic Personality Inventory (MMPI) except there are far fewer questions. The scoring guide suggests that the TEMPS-A can discriminate between hyperthymic, cyclothymic, dysthymic, and irritable temperaments. It is validated in the usual ways.  The relevant question is whether any diagnosis made with this checklist would deter you from treating a comorbid condition - like Adult ADHD?  It is one thing to survey a misdiagnosed group with the TEMPS-A and consider the clinical implications, but another to consider the presenting problem possible ADHD and whether it should be treated.

The arguments in reference 2 about overdiagnosis, the existence of adult ADHD, and the idea that ADHD can occur in adults without a childhood diagnosis can be challenged with the facts and references provided here.  The fact that we are in the midst of a multigenerational drug epidemic in an increasingly intoxicant permissive society does not mean that a diagnosis, treatment, or problem does not exist. It does mean that all psychiatrists from the moment they enter practice must exercise extreme caution when prescribing substances that reinforce their own use. 

The most likely cause of overdiagnosis is not because adult ADHD does not exist, not because of drug promotion (most are generic including the non-stimulant alternatives), or because MDs are careless.  There are basically two reasons.  First – the difficulty of diagnosing quantitative conditions. Second – sociocultural factors that exist in the US. Performance enhancement is built on the myth that you can tune your brain (or any organ) with supplements, nutrients, or medications to become a superior human being. The reality is you can alter your conscious state to believe that – but in the case of stimulants it is unlikely. The only real performance enhancement occurs because you can stay awake longer to read more and there is some evidence that your belief system is altered so that you believe you are smarter (14). These are just two of the reinforcing properties of stimulants that can lead to accelerated use and addiction.

That is my brief summary of the complexity of this situation. For more on my approach to adult ADHD (I only treat adults) – see this post.

 

George Dawson, MD, DFAPA

 

References:

1:  Ruffalo ML, Ghaemi N.  The making of adult ADHD: the rapid rise of a novel psychiatric diagnosis.  Psychiatric Times 2023 40(9): 1, 18-19.

https://www.psychiatrictimes.com/view/the-making-of-adult-adhd-the-rapid-rise-of-a-novel-psychiatric-diagnosis

2:  Frances A.  Containing The Adult ADHD Fad — With a Rejoinder from ChatGPT. 9/21/23. 

https://www.psychotherapy.net/blog/title/containing-the-adult-adhd-fad-with-a-rejoinder-from-chatgpt

3:  Faraone SV, Sergeant J, Gillberg C, Biederman J. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry. 2003 Jun;2(2):104-13. PMID: 16946911  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1525089/

4:  Song P, Zha M, Yang Q, Zhang Y, Li X, Rudan I. The prevalence of adult attention-deficit hyperactivity disorder: A global systematic review and meta-analysis. J Glob Health. 2021 Feb 11;11:04009. doi: 10.7189/jogh.11.04009. PMID: 33692893; PMCID: PMC7916320.

5: Polanczyk G, de Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007 Jun;164(6):942-8. doi: 10.1176/ajp.2007.164.6.942. PMID: 17541055.

6:  Kim DS, Burt AA, Ranchalis JE, Wilmot B, Smith JD, Patterson KE, Coe BP, Li YK, Bamshad MJ, Nikolas M, Eichler EE. Sequencing of sporadic Attention‐Deficit Hyperactivity Disorder (ADHD) identifies novel and potentially pathogenic de novo variants and excludes overlap with genes associated with autism spectrum disorder. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. 2017 Jun;174(4):381-9.

7: McGough JJ, Barkley RA. Diagnostic controversies in adult attention deficit hyperactivity disorder. Am J Psychiatry. 2004 Nov;161(11):1948-56. doi: 10.1176/appi.ajp.161.11.1948. PMID: 15514392.

8: Kooij JJ, Buitelaar JK, van den Oord EJ, Furer JW, Rijnders CA, Hodiamont PP. Internal and external validity of attention-deficit hyperactivity disorder in a population-based sample of adults. Psychol Med. 2005 Jun;35(6):817-27. doi: 10.1017/s003329170400337x. PMID: 15997602.  

9:  Saklayen MG, Deshpande NV. Timeline of History of Hypertension Treatment. Front Cardiovasc Med. 2016 Feb 23;3:3. doi: 10.3389/fcvm.2016.00003. PMID: 26942184; PMCID: PMC4763852.

10:  Kotchen TA. Historical trends and milestones in hypertension research: a model of the process of translational research. Hypertension. 2011 Oct;58(4):522-38. doi: 10.1161/HYPERTENSIONAHA.111.177766. Epub 2011 Aug 22. PMID: 21859967.

11:  Murphy KR, Gordon M.  Assessment of adults with ADHD. In: Barkley RA. Attention-Deficit Hyperactivity Disorder, 3^rd edition.  The Guilford Press, New York, 2006: 425-450.

12:  Mauer S, Ghazarian G, Ghaemi SN. Affective Temperaments Misdiagnosed as Adult Attention Deficit Disorder: Prevalence and Treatment Effects. J Nerv Ment Dis. 2023 Jul 1;211(7):504-509. doi: 10.1097/NMD.0000000000001626. Epub 2023 Apr 11. PMID: 37040539.

13:  Akiskal HS, Mendlowicz MV, Jean-Louis G, Rapaport MH, Kelsoe JR, Gillin JC, Smith TL. TEMPS-A: validation of a short version of a self-rated instrument designed to measure variations in temperament. J Affect Disord. 2005 Mar;85(1-2):45-52. doi: 10.1016/j.jad.2003.10.012. PMID: 15780675.

14:  Ilieva I, Boland J, Farah MJ. Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people. Neuropharmacology. 2013 Jan;64:496-505. doi: 10.1016/j.neuropharm.2012.07.021. Epub 2012 Aug 1. PubMed PMID: 22884611.

 

 

 

 

An Outstanding Paper on Atrial Fibrillation

 

I have been fascinated by atrial fibrillation since I was a third-year medical student. I was doing a Medicine rotation and examining a middle-aged man.  Listening to his heart sounds was the first time I heard the irregularly irregular heart rhythm characteristic of atrial fibrillation. It was such an outrageous and unexpected sound compared to what I was used to that I felt a little panicky. Why wasn’t this patient experiencing more symptoms and even more unexplainably – why doesn’t he sense that there is something wrong with his heart beat?  Since then, I have treated hundreds of patients with atrial fibrillation.  I ask them all if they can sense the irregular heart beat and in the people I see about half of them can.  Being a psychiatrist, diagnosing and treating atrial fibrillation is technically not my “job”.  But it is currently such a prevalent condition that a brief examination typically triggered by vital signs and noting a pulse irregularity followed by an electrocardiogram is all that is needed. Atrial fibrillation has considerable mortality and morbidity associated with the most feared complication of stroke. A good friend of mine developed renal failure from a combination of atrial fibrillation and atrial flutter and required ablation procedures to restore normal sinus rhythm.  Two relatives had strokes associated with atrial fibrillation resulting in disability and ultimately death. Both had atrial fibrillation for about 30 years.  One of them was 92 years old, using digoxin for rate control, and not on anticoagulants. The other was 92 years old, using diltiazem for rate control, and on warfarin at therapeutic doses. He had two strokes about 10 years apart on the warfarin and multiple episodes of nuisance bleeding or excessive bleeding from minor injuries due to anticoagulation that did not require medical attention.   Another friend had pulmonary complications from an antiarrhythmic drug that he was taking for a new onset of atrial fibrillation and died as a result of those complications. Sixteen years ago – I developed lone atrial fibrillation while speedskating and have been on antiarrhythmics since that time.

When you see all of those problems associated with a condition and have had it yourself, you tend to read more about it than the average person.  Reading about atrial fibrillation is generally a frustrating task. The evidence base for treating the condition seems to be in a state of flux. For years the research seemed to say that rate control and rhythm control led to equivalent outcomes. When life style measures were included, the rhythm control strategies seemed superior. Even the question of anticoagulation with novel oral anticoagulants of NOACs for stroke prevention based on a scoring system has been called into question recently.

That brings me to the topic of this blog post and that is the single best summary of information about atrial fibrillation that I have seen anywhere - at least for nonspecialists in that area.

The paper was written this year in the New England Journal of Medicine (1). It starts out with a case description of a 63-year-old man with a new onset of atrial fibrillation. The authors discuss the disease in detail and treatment recommendations consistent with their discussion. What I really like about this paper is that they are discussing phenotypes of atrial fibrillation and I do not see that happening very often in real clinical situations. The phenotypes they discuss are paroxysmal atrial fibrillation, persistent atrial fibrillation, and long-standing persistent atrial fibrillation.  They have an excellent figure in their paper that was unfortunately prohibitively expensive for me to try to post here, but the basic idea is that there are distinct anatomical and electrophysiological substrates for each of those phenotypes. In the paper the phenotypes are labeled as “clinical profiles”. His phenotypes have prognostic considerations since the authors make the point that there is a gradation in the likelihood of conversion to normal sinus rhythm and maintaining that rhythm with paroxysmal atrial fibrillation being the most likely to convert and maintain a normal sinus rhythm and long-standing persistent atrial fibrillation being the least likely to convert. Just knowing that much about atrial fibrillation is a significant advance compared with most of the clinical discussions that I hear.

The second feature in this paper that I really like is that atrial fibrillation is not necessarily a benign condition. For years the discussion has been controlling the rate or rhythm and in most cases they have been considered to be equivalent. Many clinicians have their first experience with atrial fibrillation like I had. They are doing a physical examination outpatient for another reason and they notice they are in atrial fibrillation. Depending on physiological factors that patients irregularly irregular heart rate may already be rate controlled. I have talked with many people over the years who knew that their heart rate was irregular because their spouse noticed it and they did not do anything about it for years. Atrial fibrillation is a risk factor for embolic strokes as well as dementia, death, and heart failure. Persistent tachycardia can cause cardiomyopathy and reduced cardiac output can lead to renal failure.  The authors suggest that a heart rate of 110 bpm or greater might lead to cardiomyopathy but they also suggest it can occur at a lower rate. This is an interesting observation because the most recent review in UpToDate on sinus tachycardia suggests it is generally a benign condition, however an irregular tachycardia because of reduced cardiac output is likely a different matter.

In addition, the patient can be symptomatic from reduce cardiac output with lightheadedness, dizziness, fatigue, decreased exercise tolerance, palpitations, hypertension, and an exacerbation of symptoms of underlying coronary artery disease. The lesson for psychiatrists is if you notice that a patient has atrial fibrillation it cannot be approached casually. Atrial fibrillation is associated with significant medical comorbidities such as underlying structural coronary disease, obesity, sleep apnea, hypertension, hyperlipidemia, and diabetes mellitus. If the patient has had limited contact with primary care physicians the comorbid conditions may have gone unnoticed. It makes sense to ask about additional symptoms in the review of systems as well as family history and whether that patient is seen primary care physician or cardiologist recently.  I would have no problem referring a patient with tachycardia, expected symptoms, or risk factors to an emergency department for acute stabilization if I could not get them seen in a primary care clinic.

The authors go into treatment of atrial fibrillation as basically a rate control strategy, a rhythm control strategy, and a strategy to address comorbid medical conditions.  They review rate control with beta-blockers and calcium channel blockers and prefer beta-blockers. They consider a number of antiarrhythmics and the risks and benefits of those medications.  They consider catheter ablation - either radiofrequency pulmonary vein isolation or cryoablation as being more effective for treating and preventing recurrent atrial fibrillation. The recurrence rates are relatively high even after the ablation procedures, so continued antiarrhythmic medications may be necessary.

Once a patient has stable treated atrial fibrillation, the main task for the psychiatrist is to make sure that any prescribed medications do not interfere with the cardiac medications at either the pharmacokinetic or pharmacodynamic level. QTc prolongation is a primary consideration since several of the agents used prolong the QTc interval or affect other cardiac conduction.  At the pharmacokinetic level there is the possible risk of decreased metabolism of beta-blockers and increasing bradycardia and hypotension. If I have any doubts all about medication combinations I am usually in touch with the patient’s cardiologist or primary care physician before making those changes. All of the patients I see with atrial fibrillation also have their blood pressure and pulse taken at every visit along with the description of symptoms and potential medication side effects. That means I never practice in an environment where I can't do that. I will also review how well their comorbid conditions are being treated particularly hypertension, sleep apnea, and diabetes mellitus. I will provide them with concrete advice on how to approach those problems and whether or not they need to be seeing their primary care physician sooner than scheduled.

This is also an opportunity to discuss any comorbid substance use problems. Alcohol is a definite precipitant of atrial fibrillation. I have had patients never experience another episode by stopping alcohol. I have also had patients report that they can tell when their alcohol level reaches a certain point because they will go into atrial fibrillation for several hours until that alcohol is metabolized. Stimulant medications are also a risk because they increase sympathetic tone, increase heart rate, increase blood pressure. All three of those changes can trigger an episode of atrial fibrillation.  Cannabis can have a fairly potent sympathomimetic effect by acutely lowering blood pressure leading to a reflex tachycardia. Atrial fibrillation has been reported as one of several cardiac arrhythmias associated with cannabis use (2). Interestingly, the authors of the NEJM article state that caffeine is not a precipitant. There are no qualifiers on that statement and I think it is based primarily on epidemiological evidence. Caffeine intake is always important to quantify because of its wide variability across the population and general reputation of being a benign compound. There are segments of the population that consume large quantities of caffeinated beverages every day and experience the expected side effects of anxiety (in some cases panic attacks), agitation, insomnia, and hyperadrenergic effects but they seem unaware that these symptoms are related to their caffeine consumption. Certainly consumption at that level can directly or indirectly precipitate an episode of atrial fibrillation.

That is my brief review of the NEJM article in atrial fibrillation. I encourage all psychiatrists to get a copy of this paper, read it, and keep it for reference. I am not suggesting that psychiatrists treat this condition.  I am suggesting that they recognize it - even if it has not been diagnosed and know what to do when that occurs. The reality is that in adult psychiatry no matter what your practice setting there will be a significant number of people with atrial fibrillation and other arrhythmias as well as all of the known comorbidities. You cannot treat those people unless you know about these conditions, the comorbidities, and how to avoid complications.

 George Dawson, MD, DFAPA

 

References:

1:  Michaud GF, Stevenson WG. Atrial Fibrillation. N Engl J Med. 2021 Jan 28;384(4):353-361. doi: 10.1056/NEJMcp2023658. PMID: 33503344.

2:  Richards JR, Blohm E, Toles KA, Jarman AF, Ely DF, Elder JW. The association of cannabis use and cardiac dysrhythmias: a systematic review. Clin Toxicol (Phila). 2020 Sep;58(9):861-869. doi: 10.1080/15563650.2020.1743847. Epub 2020 Apr 8. PMID: 32267189.

Supplementary:

Common and uncommon medications listed in this article used in atrial fibrillation for rate control, antiarrhythmic properties, and anticoagulation.  I added additional warnings and general type of medications that might require avoiding based on pharmacokinetic or pharmacodynamic considerations. Important to keep in mind that all medications vary in their ability to affect these mechanisms as well as therapeutic mechanisms. That includes significant differences between medications in the same class. That leads to qualifiers like "all possible mechanisms leading to complications or serious adverse effects may not be listed" (in this package insert or computerized drug interaction program). Almost every time I am seeing a patient on these medications - it requires a study of the medication combination, even if they are taking a psychiatric medication that appears to be working. Baseline cardiac symptoms related to the arrhythmia also need to be established as well as the patient's plan to obtain assistance if they worsen.

Additional qualifier (if it is not obvious). Psychiatrists prescribe beta blockers (metoprolol, propranolol, pindolol, etc). Psychiatrists can diagnose atrial fibrillation. Psychiatrists do not manage atrial fibrillation but need to know what to do acutely and how to avoid complications of the following medical therapies from drug interactions with psychiatric medications. Practically all of the antiarrhythmics in the following table are prescribed by Cardiologists and subsequently managed by primary care physicians although many patients continue to see Cardiologists in follow up. Like all areas of medicine the limits of technical expertise need to be recognized.  I worked with Cardiologists who became psychiatrists and they restricted their practice to medications prescribed by psychiatrists.  

Graphics Credit:

Bunch TJ, Cutler MJ. Is pulmonary vein isolation still the cornerstone in atrial fibrillation ablation? J Thorac Dis 2015;7(2):132-141. doi: 10.3978/j.issn.2072-1439.2014.12.46

Open Access per this Creative Commons License: https://creativecommons.org/licenses/by-nc-nd/4.0/     

They Don't Even Know What They Are Seeing.......

I was walking back from a meeting with a psychiatric colleague the other day.  There was the usual grousing about the practice environment and miscommunication and she made the following observation about why physicians and psychiatrists don't get the information they need.  She pointed out that in many cases the nonphysician  observers: "Don't even know what they are seeing."  If you are counting on people for observational data and that is true - that is a setup up for suboptimal care at the minimum and a catastrophe at the worst.

Take the case of a very basic measurement - blood pressure and pulse.  Anyone taking those measurements should be aware of the guidelines and whether or not the patient has a baseline abnormality, condition that can affect either, or medication effect that leads to changes in the vital signs.  They should also be aware of the limitations of measurement.  All of the automatic blood pressure machines in the world will not be able to assess and treat the patient unless the operators know what the numbers mean.  They also need to know that one of the problems with single operator and strictly machine operated approaches is that arrhythmias are problematic even if the blood pressure is fine.  There have been situations where I had to put together a continuing education course on blood pressure and pulse and the correct assessment of both.  That was a long time before the recent article on common mistakes made by medical students in these measurements.

If measurements that are considered routine and done hundreds of times a day are problematic what about observations that occur on the other end of the spectrum.  A common health care myth today is: "If I have a checklist and check off all of the boxes on that list that will lead me to some kind of diagnosis."   That is probably a minimization of the myth.  In the case of psychiatry, the myth is more: "If I convert a standard psychiatric assessment into a form (or a checklist) - the ultimate product of going through that list will basically be a psychiatric evaluation and diagnosis."  Systems of care who use this approach can deny these myths as much as they want but I see this happening every day. Organized psychiatry and the DSM approach to diagnostic criteria is partially responsible, although the manual does say that it can't be used by anybody.  It doesn't say who specifically should use it and it does not suggest (like Kendler) that it is an indexing approach.

Looking at the graphic at the top of the page illustrates why a form or a checklist does not suffice.  The observer/psychiatrist in the drawing is doing more than asking the subject a series of yes or no questions.  The psychiatrist is looking for patterns in symptoms (medical and psychiatric), what is happening in relationships with the person (including the relationship to the psychiatrist), and the person's conscious state - specifically whether there has been a departure from baseline.  There is often a balance between historical detail, phenomenology, the person's ability to describe what has happened and a plausible scenario based on probability estimates from the psychiatrist's previous experience.  Any psychiatrist who has been trained in many presentations of complex psychiatric illness is more likely to see those patterns than somebody who has not been.

To illustrate some of these concepts I will describe several cases that are all what non-psychiatrists (nonphysicians and other physicians) called hysteria. Hysteria is an old word that dies hard.  The DSM equivalent is histrionic personality disorder.  The generic use of the term suggests a person who is overly emotional, dramatic and attention seeking but there are 8 diagnostic criteria that are unchanged between DSM-IV and DSM-5.  Many clinicians opt for the term Cluster B - a DSM-IV originated term that grouped personality disorders in groups according to some common diagnostic features.  The Cluster B group included individuals that often appear dramatic, emotional, or erratic.  Those personality disorder diagnoses include antisocial, histrionic, narcissistic, and borderline.

The rule-in criteria (significant impact on life circumstances and onset when you expect a personality disorder to occur) and the rule-out criteria (not due to another mental or physical disorder) are predictable for any causal reader of a DSM and could be included on any checklist or form.  How does all of that play out?  Well here are a few examples:

Hysterical patient #1:   A 30 year old woman presents for a therapy intake.  She is mumbling and laughing.  The therapist describes her as "odd and having an odd affect."  She alludes to some suicidal behavior in the past but is smiling and joking about it.  The therapist has the impression that she is manipulative and overly dramatic.  He contacts the clinic psychiatrist and says that she is histrionic but he is concerned about her suicide potential.  The psychiatrist sees her that day and makes a diagnosis of bipolar disorder-mixed type with psychotic features.  The patient is eventually stabilized on lithium and an atypical antipsychotic.

Hysterical patient #2:  A 25 year old woman is being treated on a general medicine ward for dehydration from a respiratory infection.  She suddenly gets tearful and agitated.  Family members visiting have to physically restrain her when when she tries to get out of bed.  She starts to make very loud high pitched vocalizations.  A psychiatrist is called to go in to assess hysteria and possibly sedate the patient.  The psychiatrist sees an agitated young woman who is not able to respond coherently to any examination questions.  Brief neurological examination suggests increased intracranial pressure is the problem and the patient requires immediate transfer to a neurological intensive care unit. 

Hysterical patient #3:  A 58 year old man is referred acutely from a therapist for acute panic attacks and "probable Cluster B" personality traits.  He has recently retired due to osteoarthritis of the knees.  He had no earlier history of panic attacks but the therapist thought that he was overly dramatic at the initial session 2 days earlier when he was unable to relax and breathe normally with behavioral techniques that are usually effective.  The psychiatrist gets a history of the patient needing to abort an exercise stress test two weeks earlier due to the arthritis and having  a prolonged period of immobility at home due to sore knees. During that time he developed acute shortness of breath.  The episodes of anxiety that he described were secondary to shortness of breath and not panic attacks.  The psychiatrist sends the patient to the emergency department where an acute pulmonary embolism is diagnosed and he is admitted to the ICU.     

These are just a few examples restricted to one collection of psychiatric symptoms that illustrates what my colleague was referring to.  The value of psychiatric training goes far beyond what is in the DSM and what checklists and templates can be extracted from it.  I have never really met a psychiatrist who was focused on the DSM probably because it is implicitly evident to us that it is an index more than a diagnostic manual. We are focused on what is not in the DSM and as far as I know that is not well documented in many places.  Those are the patterns associated with clinical practice and that should have been gleaned along the way with medical training.  The DSM doesn't tell you how a pulmonary embolism presents. It is possible that you night have never seen one. But in medical training I can guarantee that it was discussed somewhere along the line in the differential diagnosis of dyspnea.  I can guarantee that one of those attendings discussed the phenomenon of the healthy young adult immobilized by air travel who gets off at their destination and suddenly has an acute pulmonary embolism. All of those features and urgencies should be in a physicians conscious state when they are seeing the whole patient and not some DSM/checklist version of a patient.

This brief post also illustrates the biasing effects of language.  What  does "Cluster B" really mean?  Aren't people who are acutely medically (or psychiatrically) ill dramatic, emotional, or erratic?  Hysteria is an extremely biasing term that over the centuries has been applied selectively to women rather than men.   The examples above illustrate that point.  If you are seeing the world through DSM language and that is your only lens - you are by definition not seeing the whole patient.  The list of possible errors in that landscape is very large.

There are a number of constraints that will get  in the way of a trained psychiatrist trying to see the whole patient.  Inadequate time is one, but time frames vary significantly.  Diagnosing a life threatening medical problem upon seeing a patient may take a matter of minutes and is clearly the most important diagnosis.  Seeing a long series of new patients briefly to prescribe treatment will necessarily mean that certain features in the above diagram will be missed.  So-called measurement based care depending on a large number of checklists to "quantitate" affects or other psychiatric states makes the same mistake.  Collaborative care where a psychiatrist looks at these rating scales and recommends treatments makes the same mistake.

The best assurance that the critical aspects of care will not be missed is to be sitting across the room from someone who has been taught all of the critical aspects of care.  That process is complex and as far as I know has never been adequately described.  A first approximation is whether that person knows what they are seeing and how to respond.

George Dawson, MD, DFAPA     

Indexing Versus Diagnosis - A Non-trivial Difference?

There was an interesting article written by Kenneth S. Kendler, MD in this month's American Journal of Psychiatry.  It addresses a phrase that I have seen in typed evaluations that causes me to cringe: "The patient does/does not meet criteria for major depression."  I was asked why that phrase bothered me so much and I basically pointed out that I don't care whether a person "meets criteria" for a specific DSM criteria - the overall assessment was more important to me.  Kendler describes the difference in terms of phenomenology - are there other aspects of depression that merit further description than what is in the DSM?  That seems true to me as well as, the time domain of symptoms development and how some of the critical symptoms may have developed.  On a developmental basis - sleep, anxiety, and depression all may have different time frame and given the length of time that the DSM approach has been around - there has been very little discussion of some of the key convergences and divergences.  Is primary insomnia beginning in middle school associated with depression in the twenties - the same problem as no insomnia in childhood and depression in the twenties.

To study the issue Kendler looks at 19 textbooks and 18 symptoms domains described in each of those textbooks.  He has specific criteria for textbook selection that resulted in 19 texts from 5 countries published between 1899 to 1956.  He included full criteria published by Wendell Muncie in 1939 and Aubrey Lewis in 1934 as being particularly instructive.  He looks at the number of authors describing a particular symptoms and additional descriptors of the symptoms they found in depressive states.  Just looking at neurovegetative states, the results are interesting.  The atypical depressive symptoms of hypersomnia and increased appetite and weight gain were essentially absent. Fourteen authors described sleep problems as initial insomnia or non restorative sleep.  Three authors described early morning awakening.  Poor appetite was listed by 10 authors and weight loss by 9 authors.  Anhedonia was listed by seven authors.  Kendler provides a detailed analysis of the remaining symptoms and how many of the authors consider these symptoms to be representative of depression.

One of the most instructive aspects of the paper was a direct comparison with DSM5 criteria across 18 symptoms, whether they are covered in the DSM and to what extent.  The symptoms not covered included volition/motivation, speech, other physical symptoms, anxiety, and depersonalization/derealization.  Experienced clinicians commonly encounter depressed people with all of these symptoms in everyday practice.  As an example, some of the most severely depressed people that I have treated were somatically focused to one degree or another on a continuum to the point of somatic delusions.  Adhering to DSM5 criteria would leave out the most important feature of their illness.  A more complete description of these symptoms allows for a better demarcation of the line between depression and psychotic depression - a critical line for developing a treatment plan.  Another critical aspect is the relationship between anxiety and depression.  The DSM tends to sacrifice a broader phenomenological approach for narrow, easily determined diagnostic markers.  Instead of describing the anxiety associated with depression, depressed patients often end up with additional diagnoses of anxiety disorders and in the DSM field trials it appears that anxiety and depression morph into on another and the criteria appear to have low diagnostic reliability in that context.

The broader concept from Kendler's philosophical perspective is whether meeting criteria is that same thing as having the disorder.  From a phenomenological perspective it is certainly possible to produce detailed analysis of patients that do not resemble one another in many regards.  Considering the fact that depression is always mapped onto unique conscious states that should not be too surprising.  Kendler's idea is that the DSM5 criteria do a "reasonable but incomplete job of assessing the prominent symptoms and signs of depression in the western post Kraepelinian tradition  ".  The idea of indexing cases of depression from what is not depression is relevant here.  I think that he should have been a little more specific in his criticism.  I don't think they do a reasonable job when they are not part of a psychiatric assessment by a psychiatrist who has enough time to do a good job.  Taking the DSM5 criteria and converting them into a checklist and applying that to the masses comes to mind.  This is probably the most absurd conclusion to the indexing concept, surpassed only by telling those who are screened that "you meet criteria for depression and that meets our health plan criteria to start citalopram".

 Kendler points out the consequences of reifying diagnostic criteria to the point that they become distinct disorders in the absence of any quantitative markers.  Andreassen made similar arguments about DSM technology and the death of an interest in psychopathology in a previous paper (2).  Both authors seem to miss the mark in terms of what is really missed here.  The diagnostic nosology has shifted from a relative simple mind based paradigm to one that purports to pick up extreme conditions at the fringe of human behavior.  The accuracy of those diagnoses is less as the described disorders get more common.  Human consciousness appears to be the critical variable here and there remain very few commentators on this issue.  Psychiatric disorders become very complex once the psychiatrist goes far beyond symptom lists and even personality disorders and what is commonly considered personality traits to recognizing that the person in front of you is a truly unique conscious state associated with a unique neurobiological state.

              

George Dawson, MD DFAPA



References:

1: Kendler KS. The Phenomenology of Major Depression and the Representativeness and Nature of DSM Criteria. Am J Psychiatry. 2016 Aug 1;173(8):771-80. doi: 10.1176/appi.ajp.2016.15121509. Epub 2016 May 3. PubMed PMID: 27138588.

2: Andreasen NC. DSM and the death of phenomenology in America: an example of unintended consequences. Schizophr Bull. 2007 Jan;33(1):108-12. Epub 2006 Dec 7. PubMed PMID: 17158191; PubMed Central PMCID: PMC2632284. (full text)


Attribution:

Quote at top is from reference 1 by Dr. Kendler.

Gout - Another Comparison Illness

The word gout in the above opening sentence from the chapter in UpToDate (1) can be replaced with any one of the major psychiatric disorders.  Gout is an extremely painful arthritis affecting one or more joints during an acute attack.  The arthritis is caused by the deposition of monosodium urate (MSU) crystals in the joint.  In a recent survey gout sufferers describe the pain as the worst pain they have ever experienced in their life - worse than childbirth or a heart attack (2).  Unlike psychiatric disorders gout has a gold standard diagnosis of the direct observation of uric acid crystals as being birefringent in a polarizing microscope, but only about 10% of gout sufferers ever has this test done.  The epidemiology of gout in the USA suggests that the prevalence is increasing to about 3.9% of the population or about 8.3 million people.  It is more common in men (5.9%) than women (2.0%).  There is an expected increase associated with obesity, hypertension, metabolic syndrome and aging.  Certain medication like diuretics can also cause increases in uric acid levels. but most people with hyperuricemia do not have gout.  The misdiagnosis of gout is common with gout sufferers being diagnosed with sprains and other forms of arthritis.  The inflammatory response is so striking that a misdiagnosis of cellulitis can also occur.  Searching Medline, I could not find a single study on the rate of misdiagnosis of gout.  Common biases that affect misdiagnoses include the over reliance on uric acid levels and demographic factors like age and sex of the patient.  Some earlier guidelines suggested an empirical trial of medication to lower uric acid levels and if that was ineffective to consider other diagnoses.

The pathophysiology of gout is interesting because it has been historically viewed as a disorder of uric acid intake, overproduction or undersecretion.  Intake is from dietary sources and there are numerous  resources that examine the purine content of foods.  Alcohol intake also directly increases uric acid production through increased metabolic demands by the liver.  The dietary approach is not uniformly accepted by physicians as a useful approach to treatment.  Many consider it to be a minor contributor to serum uric acid levels.  There is some data to support the use of low fat dairy products as a protein source and Vitamin C as a way to decrease the frequency of acute attacks.  Common claims include the use of grape and tart cherry juice as ways to decrease uric acid levels.  Internet information suggest that grape juice transiently lowers level but tart cherry juice provide more permanent decreases.  The only medical reference that I could find on grape juice was dated (4), but the references on tart cherries and cherry juice seemed excellent (5,6).  One group of authors (5) suggested that after 4 months of ingesting cherry juice there was a 50% reduction in gout attacks and patients were able to stop regular intake of non-steroidal anti-inflammatory after 60 days.  Cherry juice intake also protected patients with elevated uric acid levels from attacks.  In another study they used pomegranate juice as a comparator and it had no effect on the frequency of gout attacks.  Apart from the cherry juice evidence there is also some controversy about whether high purine content vegetables are as likely to precipitate a gout attack as meat products with high purine content.

Xanthine metabolism is intimately liked to glycolysis, so that increased metabolic demands can lead to increased uric acid production.  Common examples of how these pathways are activated in gout include excessive alcohol intake with increased metabolic demand and excessive intake of sugar sweetened beverages.

Uric acid secretion and reabsorption is captured in this graphic that attempts to address both the transport mechanisms as the uric acid transportasome and the expectedly complex genetics.  Thinking about the proteins coded for in uric acid metabolism and the transportasome,  this is clearly another complex polygenic disorder.  The diagram depicts uric acid transport in the proximal renal tubule.  The complexity of the involved mechanisms has increased significantly in the past decade.  Sodium dependent monocarboxylate transporters SLC5A8, SLC5A12 and SLC13A3 allow uric acid to accumulate in the cell.  A number of transporters allow for uric acid secretion.  In the case of OAT1 and OAT3 the direction of uric acid transportation is not clear.  PDZK1 is involved in assembling the transporter complex.  Genetic variants at all of these levels are associated with gout.

From: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7)

Merriman's review of the genetics of gout emphasizes how the complexity of the disorder is not appreciated.  Preliminary genetic studies for example indicate that there are hundreds of potential genotypes affecting the involved proteins as well as epigenetic factors to explain the environment influence on the genomics, but they would only account for about 10% of gout patient with elevated levels of uric acid.

The lack of a complete explanation for gout based historical precedence has led some innovative researchers to look for an explanation in the inflammatory arm of the illness rather than the deposition of MSU crystals.  Gout is a highly inflammatory condition in the acute phase and there has been scant attention paid to potential phenotypes.  Some patients will get very localized pain and swelling in a clearly demarcated joint space.  Other will get marked swelling, edema, erythema, in multiple joints of the ankle and foot.  In some cases there is inflammation and swelling of the surrounding tendons and connective tissue.  In other extreme cases there is blistering of the skin surface over the affected joint.  Gout gives meaning the to the term "hot joint".  The most straightforward explanation for the inflammatory response was initial complement protein activation at the surface of the MSU crystals.  That leads to phagocytosis of the crystals by macrophages and generation of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, and TNFα).  Neutrophils are recruited and superoxide and IL-8 are generated.  Macrophages eventually take up MSU crystals and apoptotic neutrophils and generate transforming growth factor (TGFβ).  MSU crystals are coated with apolipoprotein B (ApoB)  and ApoE blocks further activation of complement proteins.  The inflammation resolves and the joint is reset back to baseline.

There are alternate mechanisms proposed  that involved the NLRP3 inflammasome.  That leads to caspase-1 activation and secretion of IL-1β, IL-18 and other proinflammatory cytokines (IL-6, IL-8 and TNF).  That leads to neutrophil infiltration of the joint and periarticular tissues.   The  authors in reference 8, emphasize the importance of the IL-33/1RL1 axis and polymorphisms in genes that code for IL-33, IL-1RL1, IL-23R and STAT4 as candidate genes for the inflammatory response in gout.  They determined that the IL-23R rs10889677 AC or CC genotypes were much more likely to develop gout than the AA genotype.  Other research groups have determined associations with inflammatory candidate genes and rheumatoid arthritis, asthma, Alzheimer's disease and Crohn's disease.  

What  are the implications for psychiatry and why is a psychiatrist interested in the details of the inflammatory response?  The first reason is the diagnostic process in medicine and the myth the gold standard or some kind of biological test.  In the case of gout a biological test exists, but hardly anyone uses it.  There are good reasons for that.  It takes a considerable amount of skill to successfully aspirate an inflamed joint.  If there is significant inflammation around the joint that means pushing a needle through all of that inflammation to get to the joint.  Physicians vary significantly in their ability to insert needles into joints and based on that skill level - it may be good idea to avoid a test even if it is the gold standard.  There is also a likelihood that even when the gold standard test is done, the test misinterpretation rates are high - maybe close to 50% according to a poster session mentioned in one of the references.  The second reason is that there is a diagnostic feature here that is almost pathognomonic of the illness, even without that feature.  A person with acute onset of joint pain, in the absence of other conditions is highly likely to have gout.  The Agency for Healthcare Research and Quality and the American College of Rheumatology/European League Against Rheumatism collaborative initiative have taken two different approaches in providing assessments of gout diagnosis algorithms with and without a gold standard test and assessed their accuracy based on available data.  Third, inflammation has current and historical importance in psychiatry both as a treatment and potential etiology for psychiatric illness and there may come a time when psychiatrists need to know more about it on a routine basis for refining diagnosis and treatment methods.  Finally, complex polygenic illnesses are difficult to diagnose and treat.  That is becoming more apparent as molecular biology shows us that the first efforts at determining the pathophysiology of these disorders may have been grossly correct - but that the diagnosis requires a lot of refinement in order to capture the full range of pathophysiology that may account for the illness.     



George Dawson, MD, DFAPA




1:  Becker MA.  Clinical manifestations of gout.  In: UpToDate,  Schumacher HR, Romain PL (Eds), UpToDate, Waltham, MA.  (accessed on July 10, 2016).

2:  Liddle J, Roddy E, Mallen CD, Hider SL, Prinjha S, Ziebland S, Richardson JC. Mapping patients' experiences from initial symptoms to gout diagnosis: a qualitative exploration. BMJ Open. 2015 Sep 14;5(9):e008323. doi: 10.1136/bmjopen-2015-008323. PubMed PMID: 26369796; PubMed Central PMCID: PMC4577947.

3: Newberry SJ, FitzGerald J, Maglione MA, O'Hanlon CE, Han D, Booth M, Motala A,Tariq A, Dudley W, Shanman R, Shekelle PG. Diagnosis of Gout [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Feb. Available from http://www.ncbi.nlm.nih.gov/books/NBK350137/ PubMed PMID: 26985540.

4:  LOEPER J, TISSEYRE JC. [Contribution to the uricosuric property of grape juice]. Prog Med (Paris). 1960 Nov 24;88:384 passim. French. PubMed PMID: 13763105.

5:  Schlesinger N, Schlesinger M. Previously reported prior studies of cherry juice concentrate for gout flare prophylaxis: comment on the article by Zhang et al. Arthritis Rheum. 2013 Apr;65(4):1135-6. doi: 10.1002/art.37864. PubMed PMID: 23334899.

6:  Zhang Y, Neogi T, Chen C, Chaisson C, Hunter DJ, Choi HK. Cherry consumption and decreased risk of recurrent gout attacks. Arthritis Rheum. 2012 Dec;64(12):4004-11. doi: 10.1002/art.34677. PubMed PMID: 23023818; PubMed Central PMCID: PMC3510330.

7:  Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10;17:98. doi: 10.1186/s13075-015-0609-2. Review. PubMed PMID: 25889045; PubMed Central PMCID: PMC4392805.

8: Liu S, Zhou Z, Wang C, Guo M, Chu N, Li C. Associations between interleukin and interleukin receptor gene polymorphisms and risk of gout. Sci Rep. 2015 Sep 24;5:13887. doi: 10.1038/srep13887. PubMed PMID: 26399911.

9: Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, Brown M,Choi H, Edwards NL, Janssens HJ, Lioté F, Naden RP, Nuki G, Ogdie A, Perez-Ruiz F, Saag K, Singh JA, Sundy JS, Tausche AK, Vaquez-Mellado J, Yarows SA, Taylor WJ. 2015 Gout classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2015 Oct;74(10):1789-98. doi: 10.1136/annrheumdis-2015-208237. Erratum in: Ann Rheum Dis. 2016 Feb;75(2):473. PubMed PMID: 26359487; PubMed Central PMCID: PMC4602275.

Supplementary 1:

Disclaimer - this is not medical advice on how to treat gout, but my personal experience.  See your personal physician if you think that you may have gout or any type of arthritis.

I have had a lot of personal experience with gout since medical school. That is where I experienced my first gout attack.  I was up cramming for a Pathology test, eventually went to bed and was awakened at 3AM with intense left ankle pain. People have various descriptions for gout pain.  The one I have settled on is that it feels like your foot is being burned off with a blowtorch. The pain and inflammation are so intense that I end up feeling physically ill for days until the acute episode resolves. That first time I went the ED of the county hospital affiliated with my medical school. I was there for about 8 hours and at some point, the Orthopedic surgery team came by and aspirated my ankle joint between trauma surgeries.  They also asked my wife to leave the room and asked me if there was any chance that I had contracted gonorrhea -  another cause of acute arthritis.  I was given a prescription for acetaminophen with codeine and discharged home. Acetaminophen with codeine is not an anti-inflammatory medication and it does not treat gout – so the acute episode basically resolved on its own after a few days.

I was lucky enough to have gone to a medical school where the head of Medicine was a Rheumatologist who ran a lab that analyzed joint aspirates. I got in to see one of his associates and the diagnosis was confirmed based on that sample. That was after several visits to the Orthopedic surgery clinic where may leg had been casted in a splint for a presumed traumatic injury that I could not recall.

Over the intervening 30+ years, I would estimate that I have had about 20 attacks, 5 of them severe. In that time, I saw one excellent Rheumatologist who told me that given the fact that I do not have hyperuricemia or secondary manifestations of gout (tophi, nephrolithiasis) – I could treat the episodes symptomatically as they occur. Over the years that has been a moving target. A few of the regimens have been:

1. Indomethacin 50 mg TID for acute attacks.

2. Prednisone 60 mg/day x 5 days.

3. Prednisone 40 mg/day x 5 days.

4. Prednisone 40 mg/day x 5 days then 20 mg/day x 5 days then 10 mg/day x 5 days then 5 mg/day x 5 days.

5. Naproxen 250-500 mg BID for acute attacks

6. Vioxx (rofecoxib) 25-50 mg/day for acute attacks. Vioxx was taken off the market for cardiovascular and cerebrovascular side effects.

7. Colchicine – tried briefly and could not tolerate.

It should be apparent that seeing 10 different doctors for gout results in 10 different prescriptions. I can say that in my case, I do not tolerate high dose prednisone very well for even brief periods of time and that 20 mg will terminate an acute attack of gout within hours. The short course of prednisone always result in a flare-up of the primary attack and a tapering course of 15-20 days is usually needed, especially if that physician advises to not use prednisone and NSAIDS at the same time. My current goal is to get off of prednisone as soon as possible and on to naproxen.

The diagnostic problems with gout have also led to several misadventures. I recall being seen by a primary care MD who I had never seen before for acute wrist pain that was probable gout.  He insisted on inserting a needle into my right radiocarpal joint, even though I told him I had a diagnosis of gout by one of the top experts in the world at the time.  He ended up aspirating a piece of the joint capsule, instead. I have also had gout of the wrist and ankle misdiagnosed as cellulitis, even though I told that physician this was gout and I had a longstanding diagnosis of gout.

People tend to attribute the tremendous physician variation in diagnostic processes and treatments in complex polygenic illnesses to the “art of medicine.” I have always considered that an inaccurate phrase. I don’t consider anything about medicine to be artsy. Medicine including psychiatry is a technical field and physicians need to know technical details. The variation is accounted for in biological complexity that adds to the varied presentations of illness and the selection of treatments along a continuum from being very effective to not so effective for a particular person.

I also wanted to add a bit about the genetic approaches to illnesses especially the one mentioned in reference 8.  Today it is possible to search your own DNA for genotypes that are found in the literature to correlate with illnesses.  When I did that for the candidate gene for gout mentioned in the paper,  I found that I have the rs10889677 SNP with a C/C genotype on the IL23R gene on Chromosome 1.   According to this paper that may better explain why I am bothered with gout than the steady state of uric acid flux in my body.  My uric acid levels are always normal.

So much for what you learn in medical school.


Supplementary 2:

Total ICD-10 Gout Diagnoses

Total ICD-10 Mood Disorder Diagnoses

And you thought the DSM had too many diagnoses?


Attribution:

1:  The diagram on factors affecting the reabsorption and secretion of uric acid is form: Merriman TR. An update on the genetic architecture of hyperuricemia and gout. Arthritis Res Ther. 2015 Apr 10. (reference 7) and posted here per the conditions of their open access license.