Preliminary Look At Structured Treatment Planning

I recently posted an early view of an approach to look at the treatment planning discussion that occurs at the end of a psychiatric interview. I thought that the next step would be to see if this approach works in the real world.  My current real world involves doing 1 hour evaluations with anywhere from 15-20 minutes of that time focused on a discussion of the treatment plan and that does include the option of no psychiatric treatment and in many cases other suggested treatments.  For example, some people seek treatment for acute stressors including grief that generally resolve spontaneously or are more adequately treated by individual or group counseling.  In most treatment settings where there is a triage system, these people are frequently screened out and do not see psychiatrists. That consideration directly applies to the treatment planning discussion because it affects the discussion of diagnosis, medical complications, and suggested treatments.

The graphic above shows the results of 10 interviews and the distribution of what was discussed (indicated by the orange cells) varies with individuals and general headings. The graphic is more readable if you click on it and zoom.  For example there were 13 bullet points that were covered in all 10 discussions and those points have to do with a diagnosis and specific treatments are expected.   Some topics were less frequently discussed and that generally means there were less applicable or the discussion time was reduced by a more lengthy diagnostic interview.  I have found over the years that the length of an interview depends on getting the necessary transfer of information that can lead to a working diagnosis so that treatment planning can be started.  The information necessary can be compromised by a number of factors including the patient's emotional state, their ability to describe a history with enough detail, the ability to be relatively concise, and the ability of the physician to communicate based on eliciting the necessary information and empathic listening.  That can vary significantly from physician-patient dyad to dyad.

In terms of coverage of all 50 bullet points, 30-58% of them were covered in the discussions with patients.  I don't think there is an ideal number.  The people I talked with all have unique needs and there is no cookie cutter approach to either the diagnostic process of treatment planning.  In some cases my discussion may run a little over the 15-20 minutes but that is rare.  I have received some feedback that this seems like an ivory tower approach that can only be used by psychiatrists who have unlimited time with patients. All of these interviews were conducted the same way I have interviewed and talked with people for the past 30 years.  The interview was not modified in any way.  This is not research (yet) it is real world experience.

I am in the process of modifying the form based on suggestions from other psychiatrists so this is not the final version.  At some point I think it would be useful to consider research using this kind of format to document that points covered by setting, diagnosis, and time constraints.  A basic skill that all psychiatrists need is knowing when to depart from the original reason for consultation to a more urgent need - like the need for assessing an acute medical problems, a medical problem that might represent the cause of the psychiatric presentation, or a complication of treatment.

For now, I think it works as good evidence that psychiatry is not as easy as it has been depicted.  The original depiction was by the federal government when it suggested the structure of psychiatric evaluations and treatment were not like the rest of medicine.  There were separate codes and reimbursement for psychiatric treatment that did not take into account even one section of the above template.  The adaptation to that government and insurance company practice has been to reduce discussions to the amount of time congruent with the devaluation of the cognitive process. That also led to clinics scheduling patients too close together and for briefer appointments.  There is a lower limit to the time necessary to assess and treat patients. I don't think anyone who is doing new evaluations every 20 minutes while they are talking to patients and checking off templates in the electronic health record is going to be having lengthy treatment planning discussions. This form suggests that psychiatrists need time to do what they were trained to do.

The form when it is completed with provide not only a good estimate of what was discussed with the patient but will also provide guidance on what is relevant to document. 


George Dawson, MD, DFAPA

 

Evidence Based Urgent Care

I went in to urgent care today after battling an influenza-like illness that I got on a trip to Alaska, most likely in the flight home.  The symptoms are charted in the above graphic.  Without providing too much graphic detail on the symptoms, my concern was in whether or not I might have pneumonia and needed a chest x-ray.  Although I knew this was most likely not an influenza virus, the symptoms were fairly severe.  As an example, on last Saturday August 15, I had diffuse muscle pain that was so severe, I could barely move.  In the two days I took time off from work August 18 and 19, the muscle pain was restricted to chest wall muscles.  The cough had also become productive over the past 5 days.  I thought it was reasonable to get it checked out, especially against a backdrop of asthma and chronic asthma therapy.

I took my graphic along with me and showed it to the nurse and the physician.  I told her that I had bronchitis that was probably caused by a respiratory virus.  The nurse was overtly uninterested and at one point said that all she needed was a single symptom to write down and that symptom would be cough.  As she continued writing, she kept glancing at the graphic and taking additional notes.  I wanted to say: "Just scan it in and you can stop writing.  It contains almost all of the information that you need to know."  But I didn't.  I maintained standard medical office decorum.  As Seinfeld once said: "You go from the large waiting room to the smaller waiting room and wait again to see the doctor."  The nurse took all of my vitals including an oxygen saturation and stated matter-of-factly: "They're all normal."  My enthusiastic reply of "Good" was met with dead air.

The doctor walked in and I gave him a brief history.  He looked at my graphic and wrote down a few words.  He listened to all of my lung fields with a stethoscope and then listened to my heart sounds - both through my shirt.  The entire history and exam took about 5 - 10 minutes.  And then:

"You have bronchitis.  There is probably a lot of inflammation in there.  I am going to prescribe prednisone and an antibiotic.  Levaquin is a good one for this.."

At that point, I told him that I was already on two QTc interval prolonging drugs and that Levaquin might not be a good idea.

"OK then I will look up another antibiotic.  Doxycyline is one that should work.  Yes - there is no interaction between doxcycline and your medication.  Any other questions?"

I asked him about the issue of a chest x-ray.  I had three in the last two years and it seemed like the decision was a coin toss.

"I don't think so.  You have sounds all over your lungs and not in one place in particular.  If it doesn't get better I would do a chest x-ray.  Right now it is not going to change what I do."

I walked out with scripts for doxycycline 100 mg BID x 10 days and prednisone 40 mg QDAY x 5 days.  Entire length of the visit with the RN and MD about 15 minutes and I was the only patient in that clinic.

Of course all during this time, I was comparing the topology of this medical visit and medical care to the common uniformed criticisms of psychiatric care.  Just this morning and totally out of the blue somebody sent me a link to their letter in the British Medical Journal about the fact that 70% of clinical trials of paroxetine were unpublished.  He sent it in response to a post that I had made here some time ago, and apparently was unaware of the fact that I figured out that paroxetine was not a drug that I cared to prescribe by the time I had prescribed it to a second patient.  It should be obvious that unpublished clinical trials have been a significant problem in medicine for some time and that is nothing new in psychiatry.  Seems like the prevalent bias against psychiatry rearing its ugly head again.

How about the longstanding claim that psychiatric diagnoses are not valid because there is no "test" for them.  What was the "test" I got for bronchitis?  Of course there was none.  A diagnosis of bronchitis pretty much depends on the symptoms that I walked in with.  The same symptoms on the graphic that seemed to be shunned by the RN and casually interesting to the MD.  None of the measurements in the office had anything to do with bronchitis.  They were all essentially measures to look at whether or not I had any more significant disease - actually a more significant syndrome.  When I was an intern, we thought we had a more scientific way to analyze the problem.  We would obtain sputum samples and Gram stain the samples and culture them.  Once the integrity of the respiratory epithelium is disrupted there are all kinds of bacteria that colonize the area.  The sputum samples were not useful - either in terms of pathogenesis or guiding antibacterial therapy.  Thirty years later, antibacterial treatment of bronchitis is still empirical.  No specific pathogen is identified.  The thinking used to be that sputum indicated a bacterial infection, now we know it is just sloughed epithelium from the cytotoxic effect of viruses.  Empirical treatment of bronchitis is really no different than empirical treatment of any symptom defined mental illness.  Ignoring a couple hundred specific respiratory viruses is reminiscent of a hostile criticism of psychiatric nomenclature: "It is all one disease."  By comparison, acute bronchitis is also one disease.

Another interesting comparison is symptom severity.  I spend a lot of time discussing and documenting this with psychiatric disorders.  In the case of bronchitis, there was no particular interest in severity.  No questions about subjective experience, patterns of the cough, or sputum production.  You either have it or you don't.  Of course, I know that pattern recognition was in place and the physician was looking for signs of more significant illness like tachycardia, tachypnea, diaphoresis, and cyanosis.  But there were not any questions about functional capacity and how I was being affected (again more info in the graphic.)  Psychiatric diagnosis and treatment requires close attention to severity, impact on functional capacity and sleep, and whether the symptoms are in remission.

What about the "evidence basis" of the treatment?  A charitable interpretation of the e-mail about paroxetine would suggest that author was critical of the evidence basis for its use.  It is well known that over half of the drug studies from ClinicalTrials.gov are unpublished and that a significant number of the published trials omit details of interest (3) like side effects.  That same study looked at trials in 7 different medical specialties, none of them psychiatry.

It turns out that in clinical trials those adults with acute bronchitis treated with antibiotics are less likely to be rated as improved at follow up.  Some studies show a shorter duration of cough by 1/2 day but the trade off is a significant increase in antibiotic side effects with 19% of emergency department visits for adverse drug effects being due to antibiotics (1, 2).  A direct quote from UpToDate:

"Patients with known asthma may develop superimposed acute bronchitis.  It is common that such patients seek treatment and are inappropriately prescribed an antibiotic even though they usually have a viral illness."

The UpToDate review also looks at the associated issues of overprescription of antibiotics, the 20 year CDC initiative on antibiotic overprescribing that has essentially failed and the dire consequences of developing multiple antibiotic resistant bacterial strains.  My purpose here is not to imply anything about my treatment, but to illustrate that these practices are common and there is no equivalent amount of criticism similar to that targeted at psychiatric care.  In fact, if I wanted to take on the role of pseudopatient, I could walk in to any clinic or emergency department and walk out with the same prescriptions - even in the absence of acute bronchitis.  I could simply lie about the symptoms.  Nobody is going to ask me for a sputum sample, and 6/7 asthmatics have residual wheezing that can be picked up on a cursory exam.  Of course there would be public outcry.  I would be accused of lying to hard working physicians and wasting their time.  But that same poorly conceived idea is still cited as evidence against psychiatric diagnosis.

Unlike the unrealistic critics of psychiatry, my goal here is not to embarrass anyone, or illustrate that I am better than anyone.  But how is nonpublication of clinical trials of paroxetine (a drug that I have not prescribed in over 20 years) a problem with psychiatry?  Nonpublication of clinical trials is obviously a problem for everyone.  The poor quality of current clinical trials technology is a problem for everyone and unlike the Cochrane database, I don't see the point in the exhaustive documentation of predictable low quality results - at least not much of a point.

I am also not about to attribute the differences in practice and clinical trials to the art of medicine.  This is a problem of analyzing huge amounts of data in biological systems.  There are widespread problems with clinical trial design in every area of medicine because they cannot analyze that data.  Contrary to being a "gold standard" there needs to be better stratification of heterogenous diseases whether that is depression or bronchitis.  We can only have more specific treatments when we have better characterized molecular pathology and the treatments to target that pathology.  That includes markers that would suggest which patients would respond to drug treatment and which would not.  There is a promising biomarker for bronchitis that should be treated with antibiotics right now, but it is not widely studied or widely available.

The highlights of this post have really not changed since I began pointing out that psychiatry is singled out for criticism by various people with various motivations.  Looking at the facts in this post should leave little doubt that this is merely a continuation in this trend of unrealistic and unfair criticism consistent with the dynamic I outlined in the past.

Some things just don't change.


George Dawson, MD, DFAPA



References:

1:  Thomas M. File.  Acute bronchitis in adults. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA. (Accessed on August 23, 2015.)

2:  Smith SM, Fahey T, Smucny J, Becker LA. Antibiotics for acute bronchitis. Cochrane Database Syst Rev. 2014 Mar 1;3:CD000245. doi: 10.1002/14651858.CD000245.pub3. Review. PubMed PMID: 24585130.

3: Riveros C, Dechartres A, Perrodeau E, Haneef R, Boutron I, Ravaud P. Timing and completeness of trial results posted at ClinicalTrials.gov and published in journals. PLoS Med. 2013 Dec;10(12):e1001566; discussion e1001566. doi: 10.1371/journal.pmed.1001566. Epub 2013 Dec 3. PubMed PMID: 24311990



Supplementary:

Graphic updated daily for the course of the illness:

This illness finally cleared at about Midnight on August 28, after 16 days.  The "common cold" typically lasts 2 - 3 weeks and is a significant cause of morbidity in this country.  I hope that I have also illustrated that it is also a problem in terms of treatment and a lack of real public health measures to reduce the spread of these viruses.

How Do So Many People End Up on Stimulants?

There is no question that thousands if not millions of people end up taking stimulants unnecessarily these days.  Addiction psychiatrists,  have a unique perspective on this that I thinks goes beyond a typical approach to the problem.  I like to consider it to be grounded in behavioral pharmacology and neuroscience.   For the sake of this essay I will limit my remarks to all adults who are college aged or older and should not be taking stimulants.  Neuroscientific discoveries in the area of brain maturation suggest that a significant portion of the college-aged individuals might not make the same decisions they make a decade later, but the practical consideration is that there are millions of people in college making decisions about stimulants every day.  There are several ways to look at the problem.  The best approach I can think of is to look at the various ways that patients present for treatment.  The request for stimulant treatment can be subtle or overt.  Unlike some the papers in the current literature, I don't think that the diagnostic questions here are subtle.  During an initial clinical assessment - diagnosis and treatment commonly overlap and in some cases that I will illustrate treatment considerations become primary in the initial minutes of the interview.

The general psychiatric interview has always been a screen of sorts.  My recollection is that it was typically more problem focused in the past.  Over time, that interview started to incorporate more disorders as a focus of inquiry.  On the outpatient side the disorders added been primarily Post Traumatic Stress Disorder and Attention Deficit-Hyperactivity Disorder in non-geriatric populations.  Any time a screening is being done whether it uses a symptoms checklist or a lengthy interview there is always the chance of missing the true diagnosis or adding a diagnosis that is probably not there.  Here are a few examples.

1.  "I have been depressed for the past ten years...."  An inquiry about mood disorders at some point will focus on concentration.   Impaired concentration and attention span occurs in a number of psychiatric disorders.  Combined with some developmental history and a history of chronicity it is easy to see the problem as a missed diagnosis of ADHD and initiate treatment for that disorder in addition to the primary mood disorder.  There are problems with that approach especially when the history of the mood disorder is clear and it has never been adequately treated.

2.  "I have a diagnosis of bipolar disorder - manic and these medications aren't working...."  ADHD in adults rarely presents as hyperactivity so severe that it could be mistaken for mania.  Manic episodes are also phasic disturbances making it very unlikely that there would be many patients in any single practice who were both manic and had ADHD.  In the cases where it does happen stimulant treatment complicates the treatment of bipolar disorder and can lead to worsening mania, delusional thinking and hallucinations.

3.  "My son/daughter has ADHD....."  There are two variations in this interaction.  In the first, the parent is told about the high heritability of ADHD and advised that they also probably have it and can be assessed for it or mention to their primary care physician that they may need treatment for it.  In the second, the parent of a child with an ADHD diagnosis reads the diagnostic materials and comes into an appointment and says: "You know, I have read the symptoms and think that I have them.  Should I be treated for ADHD?"

4.  "I have always had a problem reading and I was  never any good in school..."  A common approach is to view this as ADHD, do the screening and proceed with treatment.  Physicians in general have had very little training in the assessment or treatment of learning disorder and although there is comorbid ADHD and learning disorders there is also a significant population of people with pure learning disorders who do not have ADHD.

5.  "I took my friend's Adderall and felt like I could concentrate and study for the first time in my life.  I did a lot better on that test...."  The population-wide bias is that stimulants are a specific treatment for ADHD rather than a drug that will temporarily improve anyone's energy level and attention span.  There is also the cultural phenomenon of cognitive enhancement or using stimulants as performance enhancing drugs that may be driving this request.  It is known that the availability of stimulants on campuses and in professional schools is widespread.  This is associated with students selling their prescriptions for profit and availability of stimulants illegally obtained for the purpose of cognitive enhancement.  The issue is further confused by position statements in scientific journals that support this practice.  I have not seen it studied, but it would be interesting to see questions and responses about cognitive enhancement asked at student health centers and practices that see a lot of college and professional students.

6.  "I have ADHD and need a prescription refill...."  It may be true that the patient has a clear-cut documented diagnosis prior to the age of 12 (DSM-5 criteria).  But what has happened since that initial diagnosis in childhood and now is critical history.  Has there been continuous treatment since then or has the treatment been disrupted.  Common causes of disruption include stimulant side effects, symptom resolution with age,  and co-occuring substance use problems.  A detailed history of the course of treatment since childhood is needed to make the decision to continue or reinitiate treatment.

7.  "I heard you had a test for ADHD...."  This question often initiates screening at a higher level.  There are any number of places with extended neuropsychological batteries, brain  imaging tests, or EEG tests that they claim will definitively diagnose ADHD.  In fact, there are no tests with that capability.  I have heard one of the top experts in the world on ADHD make that same statement and he was also a neuropsychologist.  I have had several years of experience with quantitative EEG machines and know their limitations.   At this point several hours of extended testing adds nothing to a detailed interview, review of collateral information, and symptom checklists to basically assure that all of the questions have been asked.

8.  "My meds need to be adjusted....."  This could be a question from a person in treatment for another problem or a person already being treated for ADHD.  The unstated issue here is the underlying belief that by adjusting a medication one's mental processes will be closer to perfection.  A child psychiatrist that I work with said it best:   "The goal in treating ADHD is to get them more functional, not to perfect their functioning."  I think the unrealistic goal of perfection drives a lot of prescriptions that exceed the recommended FDA limits.  It also explains a lot of "rescue medications" superimposed on sustained release preparations like Adderall.  Anyone familiar with the pharmacokinetics of sustained release drugs should realize why rescue medications (like immediate release Adderall on top of sustained release Adderall XR) are unnecessary.

9.  "I can't stay sober if I can't get treated for ADHD....."  This can be a complicated and confusing situation.  The child psychiatry literature had suggested initially that children with treated ADHD were less likely to have substance use disorders as adults than children with untreated ADHD.  As the evidence accumulates that is less clear.  Many adult psychiatrists and some addiction psychiatrists have extrapolated those equivocal findings to mean that treating a known or new diagnosis of ADHD in an adult will improve treatment outcomes for ADHD.  There is no evidence that is true.  Some addiction psychiatrists believe that the opposite is true, that there is a cross addiction phenomenon and that treating a person with an addiction makes it more difficult to stay sober from their drug of choice.  If the person is addicted to stimulant medication and has a clear history of accelerating the dose of stimulants or using them in unorthodox ways (intravenously, smoking, snorting, etc) it is very unlikely that person will be able to take a stimulant prescription in a controlled manner.  It is also very possible that the person making this request has a long history of experiencing prescription or street drugs as being necessary to regulate mental functioning.  That can be highly reinforcing even if the effects are sustained for hours or less.

10.  "I have been sober for one month and can't focus or remember anything......" Subjective cognitive problems are frequent during initial sobriety.  The substance used and total amount used over time probably determine the extent that the cognitive changes persist, but it is a difficult problem to study for those same reasons.  Clinicians know that there are cognitive effects but there is no standard approach to the problem.  From my experience, I think that two months sober is the absolute minimum time to consider evaluating subjective cognitive problems.  Even at that time getting collateral history about the person's cognitive and functional capacity and problem solving with them on work arounds would probably be the biggest part of the treatment.

The above scenarios are not exhaustive and I probably could come up with another 5 or 10 but they are illustrative of pathways to questionable stimulant use.  The common thread here is that anyone in these scenarios can endorse all of the symptoms of ADHD.  Figuring out what those symptoms are is fairly obvious on many checklists.  One of these checklists shows the symptoms and checkboxes necessary to make the diagnosis in grayed out panels.  It is easy to fake the symptoms in an interview or on a diagnostic checklist.  It takes a lot of hard work on the part of the physician to figure out not only who might be faking but also who has the symptoms but not the diagnosis.  One of the features of the DSM that was attacked by several critics during the pre-release hysteria was the "generic diagnostic criterion requiring distress or disability" to establish disorder thresholds (DSM-5 p 21).  In the case of ADHD that is Criterion D "There is clear evidence that the symptoms interfere with or reduce the quality of social, academic, or occupational functioning."  (DSM-5 p 60).

The diagnosis of ADHD is generally not the diagnosis of a severe functional disorder.  As a psychiatrist who practiced in a hospital setting most of the people I assessed clearly met the functional criteria by the time I saw them and diagnosed severe mood disorders, psychotic disorders, substance use disorders or dementias.   Many of them were by definition unable to function outside of a hospital setting.  It is an entirely different assessment when faced with a successful professional who has worked at a high degree of competence for 20 years who presents with any one of the above problems because they think they have ADHD.  It takes more than a review of the diagnostic criteria.   It takes an exploration of the patient's motivations for treatment.  What do they hope to accomplish by treatment?

It also takes a conservative prescribing bias on the part of the prescriber.  Stimulants are potent medications that can alter a person's state of consciousness.  They are potentially addicting medications and that can result in craving or wanting to take the medication irrespective of any therapeutic effect.  The wide availability of stimulants led to the first amphetamine epidemic in the United States.   When I first started out in psychiatry, I was still seeing people who became addicted to stimulants when they were widely prescribed for weight loss.   It is well known that the medications were ineffective for weight loss but people continued to take them at high doses in spite of the fact that they had not lost any weight.  In talking with people about what drives this many people feel like they are only competent when taking stimulants.   They believe that their cognitive and functional capacities are improved despite the fact that there is minimal evidence that this is occurring from their descriptions of what they are doing at work or in their family.

There are a number of strategies in clinical practice to avoid some of the problems with excessive stimulant prescriptions that I will address in a separate post.  My main point with this post was to look at some ways that people with mild subjective cognitive concerns, addictions, people seeking cognitive enhancement, people who have been functioning well but believe that they can function better come in to treatment for ADHD and get stimulant prescriptions.


George Dawson, MD, DFAPA

Supplementary 1:  Literature was used to construct these hypothetical scenarios.

Asthma Endophenotypes? Their Implications for Psychiatry

Asthma is an annoying and sometimes fatal disease.  I have first hand experience with it because I have had asthma for at least 40 years.  Like many of my personal medical afflictions that I have posted about on this blog it was initially missed and not treated.  According to recent studies, that is still a common experience.  When I was a teenager, wheezing when mowing the lawn was apparently considered a normal reaction.  When I developed a more systemic reaction right in a physician's office, my parents were taken into an adjacent room and advised that it was apparently all "in my head" and it was some sort of psychosomatic reaction.  The psychosomatic reaction responded well to epinephrine injections and diphenhydramine.  Even when I was in medical school the treatment of asthma was shaky.  I was taking theophylline pills twice a day for several years and the patients I began treating for exacerbations of chronic obstructive pulmonary disease were all on aminophylline drips and corticosteroids.  We all had to memorize those protocols and of course know the mechanism of action (now invalidated) that was based on Sutherland's Nobel Prize winning work on cyclic AMP.  Today theophylline is considered a tertiary option for uncontrolled asthma rather than a first line treatment.

 As a fourth year medical student, I presented a very well received seminar on "slow reacting substance of anaphylaxis" or SRS-A now known to be a mixture of leukotrienes.  Eventually the treatment of asthma changed and glucocorticoid inhalers became the treatment of choice for a while.  As any primary care physician or asthmatic patient knows - no two asthmatic patients are the same.  As an example, peak flow meters are routinely used to measure asthmatic control.  No matter how badly I am wheezing, I can always max out that peak flow meter.  Asthma is a complex disease with varied presentations and the current treatment algorithms are complex with varied medications.

The diagnostic criteria of asthma seem relatively straightforward and are listed in the table below:

Diagnosis of Asthma (see additional details in National Heart, Lung and Blood Institute reference) and reference 8 below:

1.  Recurrent symptoms of airflow obstruction or airway hyperresponsiveness (eg. wheezing, chest tightness, cough, shortness of breath.) 2.  Objective assessment as evidenced by:      A.   Airflow obstruction as least partially reversible by inhaled short acting beta2 agonists as demonstrated by any of the following: -        Increase in FEV1 of ≥ 12% from baseline -        Increase in predicted FEV1 of ≥ 10% from baseline -        Increase in PEF (liters/minute) of ≥ 20% from baseline                   B.   Diurnal variation in PEF of more than 10%      C.   No other causes of obstruction

FEV1 = forced expiratory volume in 1 second (liters) PEF = peak expiratory flow

Medicine texts have traditionally used breakpoints in the above parameters to distinguish mild, moderate and severe asthma.  Despite what seem to be clear diagnostic criteria a recent review (8) in the New England Journal of Medicine states:  "Most patients with asthma have mild persistent disease which tends to be underdiagnosed, undertreated, and inadequately controlled."  The reference cited in that review points out that only 1 in 7 patients achieved good control of their asthma.  

There has been a sudden surge in research on asthma phenotypes, endotypes, and endophenotypes.  Endophenotypes are subtypes of a particular phenotype that are thought to have a common pathophysiological mechanism or in the case of psychiatry a biochemical, neurophysiological, neuropsychological maker that allows for the subclassification.  If you have attended any serious psychiatric genetics course in the past decade you have probably heard about endophenotypes.  Gottesman and Gould published a widely cited paper in the American Journal of Psychiatry in 2003 discussed the concept and its application in psychiatry.  There have been 132 references to papers on endophenotype in the Schizophrenia Bulletin alone, including a special theme issue.

A group of 5 asthma endotypes have been suggested by Corren (7).  He uses the definition of endotype as "a subtype of a condition defined by a distinct pathophysiological mechanism."  The classification was a consensus of experts looking at clinical characteristics, biomarkers, lung physiology, genetics, histopathology, and treatment response.  The following 5 endotypes were identified.

Asthma Endotypes
Allergic Asthma	Childhood onset, hypersensitivity to airborne allergens, Th2 mediated inflammatory process, eosinophilia of blood and airways, inhaled corticosteroids less effective, IgE antagonists are more effective.
Aspirin exacerbated respiratory disease (AERD)	Chronic rhinosinusitis with nasal polyps, severe bronchospasm if NSAIDs are ingested, marked blood and airway eosinophilia, increased expression of leukotriene C4 synthetase, response to cysteinyl leukotriene receptor antagonists and 5-lipoxyenase inhibitors
Allergic bronchopulmonary mycosis (ABPM)	Colonization of airways by Aspergillus fumigatus, increased fungal specific IgE and IgG, elevated blood eosinophil and total IgE levels, elevated airway eosinophils and neutrophils, requires oral corticosteroids and antifungals
Late Onset Asthma	Pulmonary function testing is more impaired than allergic asthma, marked eosinophilia in blood and airways, need oral corticosteroids.  May be mediated by IL-5.
Cross country skiing induced asthma (CCSA)	Triggered by exposure to cold dry air and intense exercise, not usually due to allergies, inflammatory infiltrate consists of lymphocytes, macrophages, and neutrophils rather than eosinophils,  airway remodeling with thickened basement membrane, not usually responsive to inhaled corticosteroids.

The tables on diagnosis and endophenotype are remarkable for their parallels with psychiatric diagnosis and research.  The available endotypes do probably not capture all of the clinical scenarios of asthma because patient behavior is a significant factor.  The endotype classification of asthma by experts is interesting in that it includes a treatment response dimension and this has been avoided in psychiatry at the diagnostic level.

Like mental illnesses, asthma is a complex polygenic disease with considerable clinical heterogeneity.  Using endophenotype approaches very similar to the approaches that have been applied to the study of schizophrenia offers the hope that classification and treatments of subtypes will be more effective and the connection between the genetics of the illness, pathophysiological mechanisms, and subtype will become more apparent.  Although the parallels with mental illness are clear, asthma researchers and clinicians treating asthma have the advantage in that they can proceed without the stigmatization that only accompanies psychiatric disorders and psychiatrists.

George Dawson, MD, DFAPA




1: Barranco P, Pérez-Francés C, Quirce S, Gómez-Torrijos E, Cárdenas R, Sánchez-García S, Rodríguez-Fernández F, Campo P, Olaguibel JM, Delgado J; Severe Asthma Working Group of the SEAIC Asthma Committee. Consensus document on the diagnosis of severe uncontrolled asthma. J Investig Allergol Clin Immunol. 2012;22(7):460-75; quiz 2 p following 475. PubMed PMID: 23397668.

2: Simon T, Semsei AF, Ungvári I, Hadadi E, Virág V, Nagy A, Vangor MS, László V, Szalai C, Falus A. Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene. Int Arch Allergy Immunol. 2012;159(2):109-20. doi: 10.1159/000335919. Epub 2012 May 30. PubMed PMID: 22653292.

3: Matteini AM, Fallin MD, Kammerer CM, Schupf N, Yashin AI, Christensen K, Arbeev KG, Barr G, Mayeux R, Newman AB, Walston JD. Heritability estimates of endophenotypes of long and health life: the Long Life Family Study. J Gerontol A Biol Sci Med Sci. 2010 Dec;65(12):1375-9. doi: 10.1093/gerona/glq154. Epub 2010 Sep 2. PubMed PMID: 20813793; PubMed Central PMCID: PMC2990267. 

 4: Bisgaard H, Bønnelykke K. Long-term studies of the natural history of asthma in childhood. J Allergy Clin Immunol. 2010 Aug;126(2):187-97; quiz 198-9.  doi: 10.1016/j.jaci.2010.07.011. Review. PubMed PMID: 20688204. 

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