More Lessons From Dermatology......

 

I have several dermatological ailments and fortunately a very good clinic of dermatologists.  The main problems have been atopic dermatitis (eczema) that did not start until I was 65 and rosacea starting slightly later.  I have posts on the pathophysiology of these conditions at the links.  I have the predisposing factors including genetics, ethnicity (fair-skinned individuals of Celtic and northern European heritage (Fitzpatrick skin types I–II), and associated conditions (childhood and adult allergic asthma) but did not get the associated atopic dermatitis at the time.  One of my siblings had both in childhood.  My father probably had rosacea but he lived during a time when dermatology treatment was generally not done by dermatologists and quite primitive. By primitive I mean, physicians tried to excise inflammatory areas from his face instead of treating them medically like they do now.

The global prevalence of rosacea is estimated at 5.46% (4).  Women are affected more than men and peak prevalence occurs in middle age (45-60 years old).  In a study that looked at how many people were untreated – the prevalence was 12.3% in Germany and 5% in Russia.  Nearly half of those affected had not received any care in the previous year despite 1/3 endorsing a significant effect on quality of life (5).  In addition to cosmetic effects rosacea is a cause of dry eyes and other significant ocular complications and sensitive skin lowering the threshold for pain and irritation.

I was doing quite well until I needed a change in sleep apnea treatment.  Three months ago I changed from APAP to BiPAP because of an increasing AHI.  Because it was running at much higher pressure, they suggested using a mask rather than nasal CPAP.  That mask led to a flareup of rosacea that required a month of treatment with doxycycline.  But even after that treatment I was left with a 4-5 mm inflammatory nodule beneath my right eye that did not resolve. 

I saw a new dermatologist today and the conversation went something like this:

Me:  “This started about 3 months ago when I tried a CPAP mask and it caused a flare-up of rosacea.  This nodular area did not clear with doxycycline.  At about 2 weeks the area of inflammation extended up into the orbital area but stopped there ever since.

Derm:  “Are you still using the triple cream?”

Me:  “Yes twice a day.  It generally works great.”

Derm:  Inspects the area with a dermatoscope in detail and then: ’Yes, it looks like inflammation.  There may be some microabscesses in the area.  It does not look like cancer or infection.  What we need to do is try a different antibiotic for a month and then if it doesn’t clear up – do a biopsy.  I am going to prescribe cefuroxime after we make sure there are no drug interactions.  I notice you are on flecainide.  We were told never to prescribe it so I want to make sure it does not interact.”

His scribe ran a drug interaction check. I set up an appointment to see him in a month and picked up the prescription for cefuroxime.  On the way to the pharmacy, I recalled enrolling patients in a cefuroxime trial for urinary tract infections.  And then I tried to recall all of the serious side effects of cephalosporins – the class of antibiotics that cefuroxime is in.  That is just the way my mind works. 

What are the lessons about psychiatry here?  I don’t think the lessons are for psychiatrists because we know better.  The lessons are basically to counter all of the misinformation about psychiatric treatment and medications from antipsychiatrists, health and wellness influencers, and other critics who don’t seem to know very much about the field.  Here goes:

1:  Diagnoses are not easy – and experts are more likely to make them and even then most are provisional.  In all my teaching about diagnostic thinking in medicine pattern matching is a significant component.  Dermatologists and ophthalmologists are the examples I typically used comparing their diagnoses to other physicians. In this case, the question is what any other physician would have diagnosed the mark on my face as and how it would have been treated.  I have actually been there and done that and it would vary from no diagnosis or treatment to acne and metronidazole. 

2:  Transdiagnostic – yes probably – you would think the term had been invented for psychiatry in the last 10 years.  It is typically used as a criticism of categorical diagnosis as in “there are just so many transdiagnostic symptoms nothing is specific?”  And "all of this comorbidity is a strike against categorical diagnoses."  The reality is there are many so-called transdiagnostic symptoms across all of medicine and many of them are more robust than psychiatric symptoms.  Rash is one of the more robust.  Rashes are transdiagnostic across the 2,000 to 3,000 conditions that produce similar rashes across disorders as well as many different rashes within the same category in the same person.  There are many different rashes (intermediate phenotypes) presenting as rosacea for example, in this case a solitary inflammatory papule.

3:  No labs?  There is no lab test for rosacea or most dermatology conditions. They are clinical diagnoses made on that basis considering all of the findings at the time of the exam.

4:  Is there a biopsy result specific for rosacea?  This is a familiar criticism of psychiatric diagnoses – there is no specific test that rules in the diagnosis. From reference 1 below: “A skin-biopsy specimen is obtained only to rule out other diagnoses, since the histopathological features of rosacea are typically not specific to rosacea.”  Rosacea is a clinical diagnosis based on history and phenotypic criteria and no specific diagnostic test is needed to confirm it (3).

4:  Prevalence and Quality of Life Considerations – prevalence and quality of life considerations for rosacea and common psychiatric disorders are similar. 

 

Rosacea studies looked at pooled prevalence (5.46%) and geographic prevalence (Germany 2.1–12.3%, Russia 5.0%, U.K. incidence rate 1.65 per 1,000 person-years (the only study to quantify incidence) rather than interval prevalence (4-6).  Rosacea is not reported in the same intervals as psychiatric disorders because it is considered a chronic relapsing condition even though a segment of these specific psychiatric disorders has that same property.  There is no cure - another frequent criticism of psychiatric diagnoses.  

Although dermatology and psychiatry use different quality of life (QoL) impairment scales, in the respective disorders about 11% of rosacea patients report severe impairment and anxiety and depressive disorders report ranges of 26-85% using a cut-off of 2 standard deviations over average community ratings (7).  There are also comorbidity considerations with high percentages of rosacea patients reporting significant levels of depression and anxiety. 

5:  Under and missed diagnoses – deference to expert diagnosis is a time-honored tradition in medicine with a more recently established empirical basis. Overall diagnostic accuracy for dermatology conditions is 37-57%.  Roughly ½ of these conditions are incorrectly diagnosed in primary care compared with dermatologists (8). That rate of misdiagnoses is similar to the rate for anxiety and depressive disorders in primary care of 40-50% (9-11).

6:  Under treatment – undertreatment follows underdiagnosis in most cases, but undertreatment can also occur when the diagnosis has been established.  In the case of rosacea delayed diagnosis can lead to progressive (granulomatous) disease and ocular complications. Seborrheic dermatitis is also a frequently co-occurring condition and patients are often unaware that they have this condition as well.

Not treating depression and anxiety on a timely basis leads to similar chronicity and conditions more resistant to treatment.  It increases both the risk of suicide and self harm with chronicity. Untreated depression and anxiety are risk factors for cardiovascular disease and substance use. Chronic pain can be increased.  Both conditions are well documented causes of significant disability.

7:  Uncertain pathophysiology – The pathophysiology of most psychiatric disorders where the possible cause has been ruled out is not known.  The same is true for rosacea.  In any similar group of medical disorders there are commonly suggested hypotheses that can be grouped by general mechanism as indicated in the table below:

8:  Uncertain medication mechanism of action/placebo response -  Since the underlying pathophysiological is unknown the mechanisms of action of the recommended treatments is unknown for rosacea and psychiatric disorders.   This means that clinical trials are needed to test the efficacy and safety of treatments and clinical care follows.

Comparisons of response rates in a selection of antidepressant and rosacea medication trials show significant placebo response in both with a slightly higher response rate in the rosacea trials (66% v. 50%).  At the same time the metrics used for effect size in both tables are not comparable.  If we change to a comparable metric like Number Needed to Treat (NNT) we see ranges of 3-8 for rosacea and 4-6 for antidepressants.  On that basis it is fair to say that response rates to rosacea medication and antidepressants are generally comparable.

The strict comparison is limited by the fact that studies have different outcome measures.  Rosacea studies use a clinician rated global improvement score.  Antidepressant trials may also have a global improvement score but more likely use clinical scales like the HAM-D or MADRS.  Both types of ratings have a consensus marker for improvement but they are not calibrated against one another.    The placebo response rates may have different mechanisms.  Both may have a regression to the mean and clinical care/therapeutic alliance component but the rosacea trials can also be affected by atmospheric conditions and additional topicals that can affect skin moisture.  Rosacea trials tend to be longer than antidepressant trials (12-16 weeks versus 8-12 weeks).

There is a question of real-world effectiveness with both conditions.  It has been studied in depression (12). It was found that for MDD, there is a 90% gap between those with the diagnosis and this receiving effective treatment (41.8% receive treatment and of those only 23.2% of those diagnosed received effective treatment.)  The RISE study (5) suggests that in a screened population for rosacea,  80% were never previously diagnosed.  Of the 20% who were 47.5% had received no rosacea care whatsoever, and only 23.7% had received topical and/or systemic drugs suggesting similar underdiagnosis and treatment as depression.   

Whenever clinical trials of antidepressant are discussed, some critics say that the lack of hard outcomes (all-cause mortality, cause-specific mortality (MI, stroke, suicide), hospitalization) as opposed to symptom-based outcomes is a major problem.  In the comparison with rosacea – all of the outcome measures are symptom-based and no evidence that treatment prevents associated or long-term complications like rhinophyma, telangiectasia, or ocular complications.  There are register based/naturalistic studies (outside of clinical trial design) that show long term use of antidepressants reduces all cause mortality, suicidal ideation, and cardiovascular mortality (13-17).  Not all analyses agree and in some cases the argument was made that it was an antidepressant class effect (18,19).  Rosacea on the other hand has not been studied against an all cause mortality endpoint because it is not associated with increased mortality.    

9:  On label - off-label -  There are currently 40 FDA approved medication for depression and 10 FDA approved medications for rosacea.  Antidepressant development dates back to the 1950s  when it was discovered that medications used to treat tuberculosis also had positive effects on mood.  Rosacea medication development began as an early topical antibiotic treatment (Sodium sulfacetamide 10%/sulfur 5% for papules/pustules).  That early treatment was before 1962.  The next development did not occur until topical metronidazole in 1988.  The only oral antibiotic approved is doxycycline 40 mg MR (Oracea) that is a combination of doxycycline 30 mg IR and doxycycline 10 mg delayed release (DR).  There are no combination medications approved despite the fact that there are compounded formulations.  As an example the Rosacea triple cream contains metronidazole, ivermectin, and azelaic acid.  Each component is FDA approved for monotherapy.    

10: Politicalization – the only real criticism I have seen of dermatologists was comedic. In an episode of Seinfeld, Jerry was trivializing what dermatologists do until he was reminded that they diagnose and treat skin cancer.  Despite the parallels to psychiatry, they have no anti-factions or health and wellness influencers suggesting they are creating more problems than they solve or negative media coverage or high visibility criticism by experts in their own field.  The head of HHS is not suggesting their treatments are overprescribed.

There is no great agitation over dermatology – their methods or treatments despite similar levels of uncertainty and clinical methods with psychiatry.  I am not suggesting there should be.  I am suggesting that psychiatry should be approached by outsiders with the same levels of acceptance that they have for dermatology.  I am also suggesting that if you have a skin condition and nobody seems to be able to diagnose or treat it – see a dermatologist. The advice applies to a mental disorder.  See an expert in that field. 

I know this does happen but there is always a delay.  And there is always plenty of misinformation about the field.  As I have posted here before – practically all of the people I saw over my 40-year career had seen somebody else first – often many different people over a number of years before they decided to see a psychiatrist. It was often the result of a referral decision.  But most importantly – don’t believe what you read in the papers whether it is health and wellness advice or recommendations by the current Secretary of HHS. 

If there is a serious problem with your mental state – see the right person.

 

George Dawson, MD, DFAPA

 

1:  van Zuuren EJ. Rosacea. N Engl J Med. 2017 Nov 2;377(18):1754-1764. doi: 10.1056/NEJMcp1506630. PMID: 29091565.

2:  Frazier W, Zemtsov RK, Ge Y. Rosacea: Common Questions and Answers. Am Fam Physician. 2024 Jun;109(6):533-542. PMID: 38905551.

3:  Dirr MA, Ahmed A, Schlessinger DI, et al. Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement. JAMA Dermatol. 2024 Jun 1;160(6):658-666. doi: 10.1001/jamadermatol.2024.0636. PMID: 38656294.

4:  van Zuuren EJ, Arents BWM, van der Linden MMD, Vermeulen S, Fedorowicz Z, Tan J. Rosacea: New Concepts in Classification and Treatment. Am J Clin Dermatol. 2021 Jul;22(4):457-465. doi: 10.1007/s40257-021-00595-7. Epub 2021 Mar 23. PMID: 33759078; PMCID: PMC8200341.

4:  Gether L, Overgaard LK, Egeberg A, Thyssen JP. Incidence and prevalence of rosacea: a systematic review and meta-analysis. Br J Dermatol. 2018 Aug;179(2):282-289. doi: 10.1111/bjd.16481. Epub 2018 May 31. PMID: 29478264.

5:  Tan J, Schöfer H, Araviiskaia E, Audibert F, Kerrouche N, Berg M; RISE study group. Prevalence of rosacea in the general population of Germany and Russia - The RISE study. J Eur Acad Dermatol Venereol. 2016 Mar;30(3):428-34. doi: 10.1111/jdv.13556. PMID: 26915718; PMCID: PMC5067643.

6:  Hilbring C, Augustin M, Kirsten N, Mohr N. Epidemiology of rosacea in a population-based study of 161,269 German employees. Int J Dermatol. 2022 May;61(5):570-576. doi: 10.1111/ijd.15989. Epub 2021 Dec 12. PMID: 34897653.

7:  Rapaport MH, Clary C, Fayyad R, Endicott J. Quality-of-life impairment in depressive and anxiety disorders. Am J Psychiatry. 2005 Jun;162(6):1171-8. doi: 10.1176/appi.ajp.162.6.1171. PMID: 15930066.

8:  Bridges C, Morris C, McElroy JA, Quinn K, Dyer J, Becevic M. Utility of Dermatology Extension for Community Healthcare Outcomes (ECHO) sessions in the adult and paediatric population. J Telemed Telecare. 2021 Jul;27(6):376-381. doi: 10.1177/1357633X19874200. Epub 2019 Sep 16. PMID: 31526083.

9:  US Preventive Services Task Force. Screening for Depression and Suicide Risk in Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2023;329(23):2057–2067. doi:10.1001/jama.2023.9297

10:  Jackson-Triche  ME, Unützer  J, Wells  KB.  Achieving mental health equity: collaborative care.   Psychiatr Clin North Am. 2020;43(3):501-510. doi:10.1016/j.psc.2020.05.008

11:  Wang  PS, Angermeyer  M, Borges  G,  et al.  Delay and failure in treatment seeking after first onset of mental disorders in the World Health Organization’s World Mental Health Survey Initiative.   World Psychiatry. 2007;6(3):177-185.

12:  Vigo D, Haro JM, Hwang I, et al. Toward measuring effective treatment coverage: critical bottlenecks in quality- and user-adjusted coverage for major depressive disorder. Psychol Med. 2022 Jul;52(10):1948-1958. doi: 10.1017/S0033291720003797. Epub 2020 Oct 20. PMID: 33077023; PMCID: PMC9341444.

13:  Chan JKN, Solmi M, Lo HKY, Chan MWY, Choo LLT, Lai ETH, Wong CSM, Correll CU, Chang WC. All-cause and cause-specific mortality in people with depression: a large-scale systematic review and meta-analysis of relative risk and aggravating or attenuating factors, including antidepressant treatment. World Psychiatry. 2025 Oct;24(3):404-421. doi: 10.1002/wps.21354. PMID: 40948054; PMCID: PMC12434377.

14:  Lagerberg T, Fazel S, Sjölander A, Hellner C, Lichtenstein P, Chang Z. Selective serotonin reuptake inhibitors and suicidal behaviour: a population-based cohort study. Neuropsychopharmacology. 2022 Mar;47(4):817-823. doi: 10.1038/s41386-021-01179-z. Epub 2021 Sep 24. PMID: 34561608; PMCID: PMC8882171.

15:  Gusmão R, Quintão S, McDaid D, Arensman E, Van Audenhove C, Coffey C, Värnik A, Värnik P, Coyne J, Hegerl U. Antidepressant Utilization and Suicide in Europe: An Ecological Multi-National Study. PLoS One. 2013 Jun 19;8(6):e66455. doi: 10.1371/journal.pone.0066455. PMID: 23840475; PMCID: PMC3686718.

16:  Korkeila J, Salminen JK, Hiekkanen H, Salokangas RK. Use of antidepressants and suicide rate in Finland: an ecological study. J Clin Psychiatry. 2007 Apr;68(4):505-11. doi: 10.4088/jcp.v68n0403. PMID: 17474804.

17:  Pan YJ, Yeh LL. Associations between mortality and exposure to psychotropic medication: A population-based cohort study for depressive disorders. Aust N Z J Psychiatry. 2023 Sep;57(9):1253-1262. doi: 10.1177/00048674221145337. Epub 2023 Jan 11. PMID: 36629047.

18:  Zhou S, Wang C, Zhang Y. Antidepressant use and all-cause mortality in depressed individuals: A real-world cohort study. PLoS One. 2025 Jul 11;20(7):e0327844. doi: 10.1371/journal.pone.0327844. PMID: 40644427; PMCID: PMC12250549.

19:  Zhuang X, Chen W, Zhan Y, Feng X, Liu C. Antidepressant selection modifies survival in depression: A National Cohort Study Using NHANES 2005 - 2018 data. Gen Hosp Psychiatry. 2026 Jan-Feb;98:33-40. doi: 10.1016/j.genhosppsych.2025.12.001. Epub 2025 Dec 3. PMID: 41351935.

20:  Andrade C. A Primer on How to Critically Read an Observational Study on Adverse Medical Outcomes Associated With Long-Term Antidepressant Drug Use. J Clin Psychiatry. 2022 Dec 7;83(6):22f14733. doi: 10.4088/JCP.22f14733. PMID: 36479952.

21:  Egeberg A, Fowler JF Jr, Gislason GH, Thyssen JP. Nationwide Assessment of Cause-Specific Mortality in Patients with Rosacea: A Cohort Study in Denmark. Am J Clin Dermatol. 2016 Dec;17(6):673-679. doi: 10.1007/s40257-016-0217-1. PMID: 27480418.

22:  Egeberg A, Hansen PR, Gislason GH, Thyssen JP. Assessment of the risk of cardiovascular disease in patients with rosacea. J Am Acad Dermatol. 2016 Aug;75(2):336-9. doi: 10.1016/j.jaad.2016.02.1158. PMID: 27444070.

Layered Psychiatry

 

I had this idea about how to present the complexity of the psychiatric diagnostic and treatment process.  After putting up a couple of diagrams for comment, I went ahead with a PowerPoint. For about 15 years I taught a course in how not to mistake a medical diagnosis for a psychiatric diagnosis.  My audience at the time was 3rd and 4th year medical students.  The lecture included a discussion of the research at the time in pattern matching and pattern completion, heuristics and common biases, Bayesian considerations, and inductive reasoning. It was generally well received but really cannot be appreciated until you are a senior clinician.  Over the time since I taught that course there also seems to be a distinct bias toward considering DSM criteria to be the basis for psychiatric diagnosis and decision making – and that is clearly a mistake.

The very first time I really became aware of the importance of pattern matching occurred when I was a fourth-year medical student.  I was on an Infectious Disease rotation and my job was to get the consults for the day, go out and see the patients we would be rounding on, do my basic compulsive medical student work up and present the findings and my ideas about the case to the attending physicians. ID docs are very bright people and like most impressive rotations I contemplated becoming an ID specialist for a while.  My patient that day had spontaneous bacterial peritonitis and the question for us was: “Do you agree with the diagnosis and current antibiotic treatment?”  I met with the patient, took a complete history, did a physical exam, reviewed the hospital course and labs, and had time for a little research. At the time I was carrying a copy of Phantom Notes for Medicine – basically an outline of the major medicine text of the day. I looked up the differential diagnosis.  I was also carrying a copy of Sanford’s guide to antibacterial therapy – the 1982 version and looked up the recommended antibiotics for peritonitis.  I was all set for rounds at that point.

Both of our ID attendings were very serious physicians. There was not a lot of banter or joking.  I anticipated presenting all of the dry facts and either getting a brief agreement, some questioning until I could no longer answer, or a long discussion of the diagnosis and treatment.  In this case the attending came into the patient’s room. He was 15 feet away from the patient and he said: “What am I seeing from right here that is a potential problem?”  Our team consisting of the ID fellow, two Internal Medicine residents, and myself – stopped in our tracks.  Nobody had an answer.  Weren’t we here for peritonitis?  How can you diagnose that from across the room?

“What is wrong with the patient’s shin?” Dr. R stated looking as serious as usual.  Sure enough there was a light pink confluent rash covering about 10 square inches of the patient’s left shin area. Dr. R happened to be an expert in streptococcal infections. He rattled off the type of strep he expected and suggested that we get a culture and send it to his lab for confirmation. I completed my presentation.  The primary diagnosis and treatment by the medicine team did not change, but now there was a new diagnosis and treatment that depended on Dr. R’s ability to recognize the pattern of this rash and make a rapid diagnosis – even though he was not expecting it.  But beyond that – we all saw the rash (although we had to be prompted to see it). Dr. R not only saw it, he processed it as a unique rash, and then a rash most likely caused by a specific kind of streptococcal bacteria. And over the next several days he was proven correct by the culture result.

Pattern matching and pattern completion are critical skills acquired by clinicians over the course of their training and careers that allows for not only more rapid diagnosis and treatment but also more accuracy in classifying ambiguous cases. Some of the examples I used in my course included ophthalmologists compared with primary care physicians diagnosing diabetic retinopathy and dermatologists compared with primary care physicians across a series of rashes.  In both cases the specialists had a higher degree of accuracy and were better at diagnosing ambiguous cases.

Cognitive neuroscience encompasses a broad range of perceptual studies starting with the early studies of visual processing by Hubel and Wiesel to more recent studies that look at the encoding that occurs in perceptual systems and what level of processing occurs at the level of primary sensory and association cortices, what the higher-level cortical structures may be, and whether or not top down processing influences perception. According to Superior Pattern Processing (SPP) theory (3), both perceived and mentally constructed patterns are processed by encoding and integration and at that point can be used for decision making or transferring approximations to other individuals.  In my example, Dr. R not only sees the pattern of the rash, but it is integrated into a feature set that has a time, visuospatial, social, and emotional context that makes it more likely that he will make a correct diagnosis. Experimental data suggests that he is not seeing the rash like any other person in the room – largely as a function of top-down control of his perceptual process.  The actual transfer of this pattern to his junior colleagues is limited because they see the rash as being a universal truth – that is they just “missed it” and therefore need to memorize what this rash looks like and not let it happen again.  They are also unaware of the processes involved in pattern matching or processing or they might have asked him about it.  For example, a logical question would have been: “What features of this rash do you notice that are suggestive of strep or a specific kind of strep?”

The question of what represents a pattern is critical to the idea of pattern recognition and processing.  There is a natural tendency to associate the term with visual or auditory stimuli, but without too much imagining patterns can clearly exist in any sensory modality and often involves the integration of multiple sensory inputs.  Cortical organization generally reflects primary sensory input to the cortex with adjacent sensory association areas and further information flow to heteromodal areas in the frontal and temporal cortex where additional integration occurs. Patterns can be sensed, encoded, recognized encoded and processed across theses systems.  The resulting integration yields a very complex array of patterns that are not intuitive.  For example, Mattson suggests that pattern processing in the human brain forms the basis of human intellect including problem solving, language and abstract thought and that it includes fabricated patterns.  Those fabricated patterns allow vicarious problems solving without having to conduct real world experiments.  The recent cognitive neuroscience of pattern processing is a significant advance compared with the old diagnostic paradigms I taught 20 years ago.  Those old experiments were basically a comparison of a non-expert to an expert diagnostician focused on a relatively basic clinical problem like a pathology slide, x-ray, ECG, or physical finding and the results were not a surprise – the experts typically prevailed in both accuracy and speed.  The sheer amount of information in a clinical encounter looks at what is essentially an infinite array of patterns, including patterns that are generally not even mentioned as being clinically relevant.

In considering what kind of patterns that need to be recognized and processed by a psychiatrist – the patterns that exist in clinical practice are a starting point.  These patterns and the associated phenomenology have been grossly oversimplified by an overemphasis on nosology. I talk with far too many people who see psychiatric diagnoses as phrases on a page in the DSM. I cringe when I hear: “The patient does or does not meet criteria for (DSM diagnosis x)”.  Kendler was correct when he referred to the DSM approach as an indexing system.  It gets people into the same ballpark, but it is not be very useful for predicting response to treatment or that specific person’s response to being ill.  It is also based on a fraction of the information collected in a psychiatric evaluation. When I consider the feature sets that psychiatrists are considering in evaluations it may look something the graphic below.  Of course, these features sets are simplified for the purpose of making a useful graphic. They will vary with the individual, their experience, social context, and culture. They will also be blended across space and have their own individual levels of integration and patterning.  Let me provide a couple of examples to illustrate these points.

Consider the above diagram as representing the possible features that must be recognized in order to assess a patient presenting to a psychiatrist and formulating and optimal diagnostic and treatment plan. My overriding concern in the first few minutes of the evaluation is whether this person really has a psychiatric disorder or a misdiagnosed medical problem and as a corollary - are they medically stable? That sounds like a basic consideration but prioritizing it is not listed anywhere in the DSM or any medical text that I know about. It does involve rapid recognition of patterns of acute medical illness particularly the most likely patterns to be misdiagnosed as psychiatric disorders and what I am seeing in real time.  It also involves pattern recognition of the thousands of psychiatric presentations that I have see that were really medical disorders.  Real life examples have included an almost immediate recognition that the patient had a stroke (many cases), seizures (many cases), meningitis, encephalitis, cerebral edema, serotonin syndrome, and neuroleptic malignant syndrome.  These rapid diagnoses were all predicated on experience-based pattern recognition rather than written criteria and these diagnoses had nothing to do with the DSM at the time.

A more cross-cutting feature in the diagram would be transference issues and defenses that can arise as soon as the initial evaluation or be indirectly evident by the patients historical description of their relationships with important people in their life.  These patterns will involve several layers in the above diagram and most importantly may suggest a psychotherapeutic intervention that can be implemented as early as the original assessment.  A similar process occurs if the patient is describing features of a major medication responsive illness.  In that situation, features from multiple layers result in a pattern that may be recognizable to the psychiatrist in terms of specific medical treatments or the urgency of those treatments.

And finally - what might the graphical representations of these pattern matching processes be?  Here are a few examples.  In the case of psychotherapeutic examples, it will depend on the exposure to specific therapies in training and practice. Each therapy has a specific pattern or series of patterns that the therapy depends up as well as patterns more specific to the conduct of therapy.  These graphics contain critical books from my library shelves with those elements.  In the case of the diagnostic and treatment process - the school of therapy and potential application are important patterns to recognize in the initial assessment.

All of these books contain symbolic representations of clinical patterns in the form of vignettes designed to assist the student of psychotherapy in learning techniques. They also contain information about the patterns of intervention that are relevant for a specific therapy and in some cases the common factors required in all successful therapies. I have graphically represented what happens in pattern processing once a theme is noted in the clinical assessment of the patient.  Clinical teaching of this process is often problem identification followed by an algorithm of features that might predict a successful course of therapy or limitations in therapy based on the students knowledge level at the time. As is true for most pattern matching and processing, the more extensive a physician's previous pattern exposure - the more likely they are to match the optimal intervention to the problem. 

I will resist making this first post of the New Year too long and wrap it up at this point with a diagram that I think pulls it all together (see below).  Each layer of this diagram consists of patterns and all of the associated pattern processing that leads to psychiatric diagnosis, formulation and treatment.  A few of the key features include the fact that diagnosis and treatment are interchangeable processes.  There will be times even during the initial information gathering that a verbal treatment intervention needs to occur and the entire interview occurs in the context of empathy and what Ghaemi, et al (4) have described as an existential psychotherapy based encounter – even if the administrative focus is on pharmacology. A second feature is that the information exchange is necessarily large if the psychiatrist and the patient are capable of it. There has been no research that I am aware of on the optimal amount of information that is required, but there are many limitations.  The advent of the electronic health record for example has led to the universal use of templates that are very restrictive in terms of information, typically dichotomous responses. A third implicit feature is the concept of patterns, what they imply for diagnosis and decision making and how there is almost a complete lack of discussion about this process in an era where diagnoses seem to have collapsed to a brief list of bullet points.  Cognitive neuroscience is a critical area of research focused these processes that I first became aware of when reading Kandel’s book “The Age of Insight” (5).  It is an area that does not typically get a lot of attention from psychiatrists, but it is a logical extension of the work done by behavioral neurologists from 20 years ago.  If we really want to focus on how psychiatrists think about diagnosis and treatment – we need to study this field, especially as the experiments get more complex.

I will wrap up this post at this point with the hope that 2021 is a much better year and that mankind is able to put this pandemic virus behind us by the summer and approach future pandemics with more science and wisdom.

 

Happy New Year!

George Dawson, MD, DFAPA

 

References:

1:  Constantine-Paton M. Pioneers of cortical plasticity: six classic papers by Wiesel and Hubel. J Neurophysiol. 2008 Jun;99(6):2741-4. doi: 10.1152/jn.00061.2008. Epub 2008 Jan 23. PMID: 18216235.

2: Poirier CC, De Volder AG, Tranduy D, Scheiber C. Neural changes in the ventral and dorsal visual streams during pattern recognition learning. Neurobiol Learn Mem. 2006 Jan;85(1):36-43. doi: 10.1016/j.nlm.2005.08.006. Epub 2005 Sep 22. PMID: 16183306.

3:  Mattson MP. Superior pattern processing is the essence of the evolved human brain. Front Neurosci. 2014 Aug 22;8:265. doi: 10.3389/fnins.2014.00265. PMID: 25202234; PMCID: PMC4141622.

4:  Ghaemi SN, Glick ID, Ellison JM. A Commentary on Existential Psychopharmacologic Clinical Practice: Advocating a Humanistic Approach to the "Med Check". J Clin Psychiatry. 2018 Apr 24;79(4):18ac12177. doi: 10.4088/JCP.18ac12177. PMID: 29701934.

5:  Kandel ER.  The Age of Insight. Random House, New York, 2012.

Graphics:

All generated by me for a PowerPoint presentation by the same name.  The photo at the top are two pamphlets that I carried as a med student along with a copy of Phantom Notes.  I was carrying them when I was in the room with Dr. R as he made the diagnosis described above.  I would not trade my medical school experience for anything. 

Eye Clinic Follow Up

I went back in today for a one week follow up of laser surgery for a retinal tear.  An acute problem always brings some issues into focus so I thought I would continue on about some comparisons of psychiatry with modern medical technology as well as some of the differences that cast some advantage to psychiatrists.   As usual there are always political implications.  I have the added advantage of showing the retinal scans from today, courtesy of the clinic.  As most patients know, experience with getting results like this from clinics is highly variable.  Most of that confusion is a direct result of the Privacy Rule that started under the Clinton administration and ended under the Bush administration.  It is complicated by CFR42, a federal regulation that directly impacts the release of sensitive data and the way it can be released.  after the recent modification to make it clearer and easier to get date, one of the clinics I go to will no longer e-mail me graphical data.  That is the outcome I expected when special interest attorneys get involved in health care law.

The visit itself went very well.  The clinic demonstrated the same efficiency.  The retinal exam included scans of both eyes by physical examination of only the affected eye.  The scribe was in the room and she picked up an error in the original note and corrected it.  The conclusion was no change in retinal opacities  (blood in the vitreous) - but well sealed off laser site with resolving retinal edema.  In the manner of most proceduralists that I have encountered, it was time for questions.  No spontaneous advice.  I carefully outlined the physical activities that I am involved in and was advised that I could resume with nor restrictions.  I had stopped taking 81 mg of aspirin a day on my own initiative and was advised that I could resume that.  The only additional information was follow up in 6 weeks and call if problems.

That call if problems is always a tricky proposition.  With the retinal opacities from the original tear the large amoeba-like blob over about 1/3 of my visual field was still there, but over the course of the day it comes and goes.  At times there are about 20-30 very small black dots floating around in that eye.  Given what I know about brain adaptation to let's say prism viewing, I wondered if my brain was adapting to the retinal opacities and only showing me the clear visual field.  There were times when it seemed worse, but I concluded that unless it was consistently worse, I should probably not call the clinic.  I arrived at that conclusion on my own. but confirmed  it with the retinal specialist between now and the next appointment.

I also thought about the time it takes me to coach patients about how to self monitor and also warn them about rare side effects.  I can spend 10-20 minutes on serotonin syndrome,  neuroleptic malignant syndrome, prolonged QTc interval, drug induced liver disease, priapism, metabolic syndrome, and diabetes mellitus.  And that is after we have discussed progress and medication side effects.  When I thought about the complication rates quoted to me for retinal/vitreous detachments and tears and the success rate of laser surgery - I am telling people about many potential complications that are a thousand to ten thousand times less likely to occur.

That is the range I am living in.  I am not complaining about it.  I think it is much more reasonable to have informed patients who understand that taking a medication is not a walk in the park or a miracle cure.  I am concerned that despite my detailed explanations and accompanying literature many people do still not understand it or just ignore it.  On the other hand I have had people with known problems like cardiac problems come back and recite everything I told them about potential cardiac problems and what to watch for.  The side effect that bothers most people is the potential for weight gain, but most of them can be assured that there is a strategy to deal with that problem.  If a medication is effective, people will want to take it even if there are potential problems with it including weight gain and ECG abnormalities.

The measurement technology used in ophthalmology is interesting.  The human retina is unique enough to allow it to be used for biometric identification.  No two retinas are identical and technically even though retinal tears have similar characteristics they are all in a unique biological landscape.

Technology clearly differentiates ophthalmology from psychiatry.  We remain stuck in the 1960s with an obsessive narrative that classifies but probably does not diagnose.  Depending on who you read, phenomenology is there to some degree.  Ophthalmologists done't really need to depend on objective descriptions of symptoms - they can see what the problem it.  I just read an article on a consensus treatment guideline  for depression that adds absolutely nothing to the field beyond what a psychiatrist has learned in residency training in the past 15 years.   At the end of the day we have no retinal scan that we can hand a patient and say: "This is your problem and this is what we did to fix it in about 1 hour."

And that is what we need.



George Dawson, MD, DFAPA


Supplementary:

I could not fit this into the body of the post anywhere but age-related retinal and vitreous diseases seem like a major oversight in medical education to me.  I studied geriatric psychiatry and geriatric medicine and the major focus was on age related causes of blindness that were essentially chronic illnesses.  As far as I can tell age-related acute retinal and vitreous problems are a major epidemic and every physicians should know how to diagnose them and how fast they need to be triaged and referred (fast).


                    

  

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.

Euthanasia And Other Ethical Arguments Applied To Psychiatric Patients

An article entitled Euthanasia and Assisted Suicide of Patients With Psychiatric Disorders in the Netherlands 2011-2014 caught my eye in this month's JAMA Psychiatry (1).  It wasn't that long ago that I recall being in the midst of a rather intense argument in a staff meeting about euthanasia in the broadest of terms.  Like many heated political arguments (I consider a lot of what goes on under the heading of ethics to be little more than politics) this one degenerated to personal terms.  The pro-euthanasia proponent ended the argument with: "Well if I am dying of terminal cancer and I want to end it, there is no one who is going to tell me that I can't do it.  Not you or anyone else."  In the dead silence that followed nobody brought up the obvious point that is the state of affairs currently.  Euthanasia proponents have always made that argument when in fact what they really want is to recruit physicians to provide them with euthanasia.  That is hardly the same thing as actively stopping them.  I would make the secondary argument that nobody really needs to be actively recruited these days.  I can't remember the last legal battle about whether a physician providing hospice care ordered too many opioids and benzodiazepines for a suffering terminally ill patient.  If I had to guess, the last time I saw that question raised in a court in the Midwest was about 20 years ago.

The concept of euthanasia in patients with psychiatric disorders is an even more complicated process.  Psychiatric disorders per se are not terminal illnesses, there is no protracted phase of increasing suffering and futile live saving measures with a fairly predictable death.  Death primarily due to psychiatric disorders occurs as a result of suicide, risk taking, comorbid medical illnesses, and severe disruptions in self care and homeostasis due to acute disorders like catatonia.  These are all relatively acute processes.  That does not mean that there are no people with chronic mood disorders, personality disorders, and psychoses.  Is the suffering in these situations acute and severe enough that euthanasia should be considered and if so, do any standards apply?

The authors of the Dutch study set out to study the characteristics of psychiatric patients receiving euthanasia or assisted suicide (EAS) in Belgium and the Netherlands.  The case studies of 66 cases were reviewed in the database of the Dutch regional euthanasia review committees.  There were 46 women and 20 men.  A little over half (52%) had made previous suicide attempts.  80% had been hospitalized in psychiatric units.  Most of the patients were aged 50-70 but 1/3 were older than 70.  Most (36) had depression and 8 of those patients had psychotic features.  The patients were described as chronically symptomatic and 26 patients had electroconvulsive therapy (ECT).  Two had deep brain stimulation - one for obsessive compulsive disorder and one for depression.  There was significant medical comorbidity.  The authors comment that there was very little social history to the point that they could not reconstruct the persons current living situation from what was abstracted.  Some of the reports contained fairly subjective data - as an example: "The patient was an utterly lonely man whose life had been a failure."  There was extensive treatment but also treatment refusal in 56%.

Twenty-one patients had been refused EAS at some point and in 3 of these cases the original physician changed their mind and performed EAS.  In the other 18 patients, the physician performing the EAS was new to the patient.  In 14 of those cases that physician was affiliated with a mobile euthanasia practice called the End-of-Life Clinic.  In 27 cases a psychiatrist did EAS and the rest were general practitioners.  Physicians disagreed in about 24% of the cases and EAS proceeded despite the disagreement.  In 8 cases the psychiatric consultant did not think that due care criteria specifying "no reasonable alternative" had been met.  The Euthanasia Review Committee (ERC) found that due care criteria were met in all psychiatric cases referred except for one.  In another case the ERC was described as being critical but in the end agreed with the euthanasia decision. It was a case of a man who broke his leg in a suicide attempt and then refused all treatment and requested EAS.

The authors come to several conclusions.  The first involves the issue that in this study the ratio of women to men was 2.3 to 1 and that is the opposite of what is expected with suicide.  They suggest that the availability of EAS may make the desire to die "more effective" for women.  Although the overall psychiatric sample was younger than the non-psychiatric EAS cases, they argue that the fact that a significant portion have significant comorbidities and this may indicate that Dutch physicians tend to self regulate EAS to a specific patient profile.  They point out that more judgment is required in psychiatric cases than in the cases involving terminal physical illness - 83% of which involved a malignancy.  They note that decision-making capacity can be affected by neuropsychiatric illness and that medical futility is difficult to determine especially when care is refused.  There were no official EAS psychiatric consultants involved in 41% of the cases.  In 11% of cases there was no psychiatric involvement at all.  Their overarching observation was that EAS for psychiatric illnesses involved making decisions about complex disorders and considerable judgment needed to be exercised.  They suggested that the decision about EAS required "considerable physician judgment" and that regional committees overseeing euthanasia deferred to the opinion of the treating physician when consultants disagreed.  

I have never seen it discussed but conflict of interest issues are prominent in any decisions about the autonomy of people who are designated psychiatric patients.  At the first level, there is the wording of the policy or statute.  There are criteria that are thought to be very objective that are used to decide if a person should be subject to civil commitment, guardianship, conservatorship, or any of the laws involving competency to proceed to trial, cooperate with one's defense attorney, or a mental illness or defect defense.  In all cases, the wording of each state's statute would seem to determine an obvious standard.  Those standards are routinely compromised in practice by any number of political considerations.  In the case of not guilty by reason of mental illness, the compromise occurs any time there are high profile cases that involve heinous crimes.  No matter how severe the mental illness, there will be a raft of experts on either side and the verdict will almost always be guilty.  At the other end of the spectrum is civil commitment.  Observing any commitment court over time will generally show the oscillation between libertarian approaches to more strict standards where need for psychiatric treatment is the more apparent standard.  The libertarian approach often uses a standard of "imminent dangerousness" as an excuse to dismiss the patient irrespective of what the statute may say.  It also seems to coincide with the available resources of the responsible county.   That is why in Minnesota the land of 10,000 lakes and 87 counties we say: "On any given day there are 87 interpretations of the civil commitment law."  Despite that range of interpretations, it would be highly unlikely that a patient who broke his leg in a suicide attempt (a case presented in this paper) would not be a candidate for court ordered treatment rather than euthanasia.  On the other hand, I do not know anything about civil commitment and forced treatment in the Netherlands.

There is no reason I can think of that a euthanasia standard can be interpreted any more logically. This Dutch study points to that.  It also points to another issue that is never really discussed when it comes to psychiatric diagnosis or the ethics and laws that apply to them.  The conscious state of the individual is never recognized.  Brain function is parsed very crudely into separate domains of symptoms, cognitions, and decisions.  The examiner or legal representative usually has some protocol by which they declare the person competent or not and the legal or ethical consequences proceed from that.  There may be a discussion of personality that is also based on this parsing process.  Very occasionally there is a discussion of the person's baseline, but that is about it.  That is a serious problem for any student of human consciousness.  Let me explain why.  I think that it is a universal human experience to experience a transient (days to months) change in your conscious state that might result in you not wanting to live.  The insult could be a physical or mental illness.  It would seem to me that at a minimum there can be multiple conscious states operating here that look like a request for assisted suicide or euthanasia.  The limits would be bounded by a completely rational decision based on medical futility and suffering on one side and an irrational decision based on the altered conscious state on the other.  The only way for any examiner to make that kind of determination is to know the patient very well over time to recognize at the very least that they are not themselves.  Doing an examination for the express purpose of determining if a person meets criteria for euthanasia in a short period of time is by contrast a very crude process.        

There is too much variability in the patient's conscious state and how that impacts treatment and ultimately recovery to consider psychiatric disorders as a basis for a decision about euthanasia and assisted suicide.


George Dawson, MD, DFAPA


References:

1:  Kim SH, De Vries RG, Peteet JR. Euthanasia and Assisted Suicide of Patients With Psychiatric Disorders in the Netherlands 2011 to 2014. JAMA Psychiatry.2016;73(4):362-368. doi:10.1001/jamapsychiatry.2015.2887.

2:  Appelbaum PS. Physician-Assisted Death for Patients With Mental Disorders—Reasons for Concern. JAMA Psychiatry. 2016;73(4):325-326. doi:10.1001/jamapsychiatry.2015.2890.


Supplementary 1:  I intentionally wrote the above post without reading the accompanying commentary by Paul S. Appelbaum, MD.  Dr. Appelbaum is an expert in forensic psychiatry and has written extensively on ethical issues in psychiatry.  Dr. Appelbaum's essay provides some additional facts, but his areas of  concern do not touch on my focus on the conscious state of the individual.

High Intensity Movement Disorders Conference

I have been a member of the Movement Disorder Society since 1993.  I decided to join after having nothing but positive experiences at the annual Aspen courses led by Stanley Fahn, C. David Marsden, and Joseph Jankcovic.   Although Dr. Marsden has passed away, the course is still being given by two of the original lecturers with additional faculty.  The level of scholarship and expertise in this conference is really not approached by many venues these days.  Each conference provided participants with a 700 page textbook like syllabus on everything that you ever wanted to know about movement disorders.  Once you attend a conference like this it is a life transforming event.  Suddenly you are following the lecturers, you read what they write and you acquire some of their books.  I changed my Neurology text to Neurology in Clinical Practice because both Jankcovic and Marsden were editors.  I also received the video material and text of Movement Disorders,  the official journal of the International Parkinson and Movement Disorder Society.

People often ask why I am member of what is predominantly a neurological society?  In Minnesota there were only three psychiatrists who were members of the organization. Stan Fahn asked me that himself at one of the conferences.  I don't remember exactly what I said, but he thought my answer at the time was acceptable.  It comes down to clinical expertise and with the confluence of the dorsal and ventral striatum - neuroanatomy.  Back in the days that I went to medical school, nobody talked about the ventral striatum only the dorsal striatum and even back then, the main clinicopathological correlate was movement disorders.  As medical students we learned primarily about Huntington's Disease, Wilson's Disease, and Parkinson's Disease.  Nothing at all about dystonias or other disabling movement disorders and their treatments.  Nothing about the last members of the generation afflicted by what we called in those days post-encephalitic Parkinson's and all of the associated neuropsychiatric morbidity.   In my rotations at Milwaukee County Hospital and affiliated institutions I saw all kinds of undiagnosed or poorly diagnosed movement disorders.   There were no movement disorder specialists in those days and no treatments except for Parkinson's.  The quality of care is slightly improved today in that referral to movement disorder specialists and an appropriate diagnosis can occur, but the total number of these specialists is very small.

That is where psychiatrists need to fill in the gap.  My initial interest was tardive dyskinesia and describing the motor disorders of patients who in many cases had never been exposed to a medication.  But it quickly became recognizing the early manifestations of idiopathic and iatrogenic movement disorders and using these diagnoses in a comprehensive diagnostic approach to the patient as well as the treatment plan.  When you take that approach it is an eye opener.  In my role as a consultant it is amazing how much undiagnosed movement disorder pathology is out there.  A couple of examples will illustrate the problem.  About 50% of young adults with childhood diagnoses of Attention Deficit-Hyperactivity Disorder (ADHD) who have been treated with stimulants have a movement disorder usually in the form of vocal tics, motor tics, or Tourettes.  About 100% of those patients tell me that nobody has ever told them about those diagnoses before.  Of course there is an exhaustive list of medication and environmental exposures that can lead to tic disorders, so there is a question of whether something occurred since childhood.  In the same population there are a group of people with choreiform movements and predominately extensor muscle tone.  They are not aware of the movement disorder and nobody has mentioned it before.  It is as though clinicians consider these movements to be part of ADHD.  One of my observations about tardive dyskinesia has been that the overall prevalence of the disorder has dropped off significantly with the advent of atypical antipsychotic medication.  That does not mean that is has gone to zero and the augmentation of antidepressants with aripiprazole seems to be a new source of that disorder.  Most significantly, the people who are at greater risk for the problem do not seem to have been carefully screened ahead of time.  They are not routinely assessed for akathisia or other early motor symptoms like micrographia, diminished arm swing,  or hypophonia.

The course was presented by three neurologists Cynthia Comella, MD; Rajesh Pahwa, MD; and Jerrold L. Vitek, MD, PhD.  It was presented by the University of Kansas Medical Center and all of the brochures and specific courses are available on this web site.  The course was unusual in its rapid presentation of topics and strict adherence to that schedule.  There were ten presentations by the faculty varying in length from 20 to 55 minutes in duration.  The morning presentations covered Parkinson's and Parkinsonism, Restless Leg Syndrome, Tremor Disorders, and Movement Disorders in Psychiatry.  The afternoon covered Dystonia, Chorea, Tics, Neurotoxin and Deep Brain Stimulation for Neurological and Psychiatric Disorders.  The entire set of PowerPoints (without the videos) was included in the course syllabus.  The slides were all very readable in a standard format.  The Psychiatric Aspects of Movement Disorders was a very interesting presentation because it covered a wide range of problems that acute care and geriatric psychiatrists come in contact with including Parkinson's Disease and the associated psychiatric comorbidity, Tardive Dyskinesia, Neuroleptic Malignant Syndrome, Serotonin Syndrome, and Psychogenic Movement Disorders.  Interest in these topics may reflect exposure to the problem.  In seeing patients with Parkinson's and psychosis for example one of the commonest problems is that antipsychotic medications will generally make their psychosis worse.  The only exception to that is clozapine and that comes with a host of comorbidities and monitoring issues itself.  One of the presenters suggested that quetiapine is a default choice in many cases even though it is not ideal and efficacy is low.  A new medication for the treatment of psychosis in PD was mentioned called Pimavanserin.  It is a selective serotonin 5-HT2A inverse agonist without significant activity at dopaminergic, histaminergic, muscarinic, or adrenergic receptors.  Practical approaches to treating dementia, anxiety, and depression associated with PD were also discussed.

The most fascinating part of the course was the section on deep brain stimulation (DBS).  A fairly detailed description of the procedure was given.  Deep brain stimulation is currently FDA approved for Essential tremor and Parkinsonian Tremor and Parkinson's Disease with humanitarian device exceptions for Primary Dystonia and Obsessive Compulsive Disorder.  This section was presented by Dr. Vitek who has a wide range of experience with this method.  Before and after videos of children and adults with disabling movement disorders were presented and the results were striking.  The general concept presented was that any "circuit disorder" was a potential candidate for DBS and that is consistent with the current literature on the subject.  The other important concept is that with DBS there are no permanent changes in the brain apart from the low risk of placement complications.  That is not true for neurosurgical techniques that have been used for the same neurological and psychiatric complications.  In the case of DBS the stimulator can be reprogrammed, turned on or off in a number of configurations, and turned completely off.  An unexpected benefit of the DBS presentation was a look at brain images from a 7 Tesla MRI scan.  The resolution of these images was incredible arguably as good as artistic renderings of brain anatomy.  Take a look at the side by side comparisons to what is currently clinically available.

Everything considered this was an excellent conference and I recommend it to anyone if it comes to your area.  I think it could be used by practicing psychiatrists who want to get up to speed on movement disorders, residents wanting to do the same thing, and psychiatrists studying for their boards in geriatric psychiatry.  It also raises a larger question of just what psychiatrists should be able to diagnose and treat?  What should they know at a theoretical level?  Based on my experience, psychiatrists seem to be the specialists that are most likely to be confronted with an undiagnosed movement disorder in patients who have seen primary care physicians or pediatricians.  Psychiatrists are also specialists who should be the experts in how to recognize and prevent motor complications of medications used to treat psychiatric disorders.  Psychiatrists have also been using the same interview and mental status exam technology for the past 50 years.  Changes need to be incremental and the logical first change that seems in order is to be able to recognize, diagnose, and treat or refer movement disorders encountered in standard psychiatric practice.  Psychiatrists interested in neuroscience with also find this a very interesting area for ongoing study.  And subspecialists like geriatric psychiatrists are probably going to need to know the difference between tauopathies and synucleinopathies.

This course is a good one to get you on that road.


George Dawson, MD, DFAPA        


Attribution:  My own picture shot at the John Rose Oval in Roseville, Minnesota.