The Majority of DSM Diagnoses Are Never Used...

 

The landscape of medical and psychiatric diagnoses that are actually used by clinicians has always interested me.  Diagnostic classifications like the DSM and the ICD are generally used for the purpose of billing and generating statistics.  There is also an implicit research function that is probably why the number of diagnoses are so expansive.  I wrote a brief comment about this on my other blog almost exactly 3 years ago.  In a study of 1,260,097 psychiatric diagnoses reported from hospital care between 2001-2007 only 16 or 4.2% of the available diagnoses accounted for 50% of the reported activity (1).  Forty-nine diagnoses accounted for accounted for 75% of the activity and 108 diagnoses accounted for 95% of the activity.  Of the total diagnoses available most were used infrequently if at all.  In a separate abstract, 32 diagnoses were not used at all and 121 diagnoses were used in less than 0.1% of cases (2).  This is an important issue that I intend to use in further posts about diagnostic reasoning in psychiatry.  This is intended as an update and moving the concept over to my main blog.

The first question when it comes to either DSM or ICD diagnoses in different clinical settings is – how many are there?  In the case of the DSM – I personally counted the diagnoses and came up with 281 diagnoses using the methods outlined in that post.  Since then, I have encountered a reference that lists the total diagnoses as 245 (3).  In an earlier DSM-III study of 11,292 general psychiatric admission 296 of 329 available diagnoses were used and the 9 most frequent accounted for 35.8% of all diagnoses (4).

Surveys of Psychiatric Diagnoses Used In Practice
N	Classification	Used/Available (%)	Skew
11,292 adults	DSM-III	296/329 (90%)	73% of diagnoses were from 6 diagnostic categories with major depression the predominate category at 23%
214,206 adults	ICD 9/10-CM	----	mood disorders (22%), anxiety disorders (21%), and substance use disorders (16%) together accounted for the majority of documented psychiatric diagnoses
13,684,154 children and adolescents	ICD 9/10 – grouped as 13 diagnostic groups and 1 other	-----	Diagnostic groups were trauma/stressor-related disorders (27%), anxiety disorders (19%), and depressive disorders (17%)
7,076 adults	DSM-III-R	------	41.2% of the adult population under 65 experienced at least one DSM-III-R disorder in their lifetime, 23.3% within the preceding year. Depression, anxiety, and alcohol abuse and dependence were most prevalent
1:  Mezzich JE, Fabrega H Jr, Coffman GA, Haley R. DSM-III disorders in a large sample of psychiatric patients: frequency and specificity of diagnoses. Am J Psychiatry. 1989 Feb;146(2):212-9. doi: 10.1176/ajp.146.2.212 2:  Barr PB, Bigdeli TB, Meyers JL. Prevalence, Comorbidity, and Sociodemographic Correlates of Psychiatric Diagnoses Reported in the All of Us Research Program. JAMA Psychiatry. 2022;79(6):622–628. doi:10.1001/jamapsychiatry.2022.0685 3:  Mojtabai R, Olfson M. Trends in Mental Disorders in Children and Adolescents Receiving Treatment in the State Mental Health System. J Am Acad Child Adolesc Psychiatry. 2025 Aug;64(8):906-920. doi: 10.1016/j.jaac.2024.08.008. Epub 2024 Aug 28. PMID: 39214290. 4:  Bijl, R., Ravelli, A. & van Zessen, G. Prevalence of psychiatric disorder in the general population: results of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Soc Psychiatry Psychiatr Epidemiol 33, 587–595 (1998). https://doi.org/10.1007/s001270050098

 I have listed several additional surveys of diagnoses in various samples.  Comparison across studies is complicated by the classification system used and whether specific diagnoses are counted or diagnostic groups.  If only groups are counted it is more difficult to illustrate the skew by weighting.  Large healthcare systems have these statistics but I am not aware of any of that data being published.  Having worked for one of those systems the data is often considered proprietary.  The data would also be affected by the clinical populations being treated.  I would expect safety net hospitals to have a much higher percentage of disability associated diagnoses than private hospitals.  I would expect the same skew between acute care settings (inpatient units and acute psychiatric services) to have a different distribution of diagnoses than outpatient clinics.  Of the 3 studies that looked at this issue above using DSM criteria – most DSM diagnoses are used infrequently if at all.

What about the criticism of the proliferation of diagnoses?  I expect to see the usual discussion of this issue as the DSM-6 is hyped as a controversial topic over the coming years.  We already know the answer to the question but everyone will need to pretend that we don’t. By my count the DSM diagnoses peaked with the DSM-IV.  A lot of the controversy about diagnostic proliferation will start by saying the DSM-I had 106 diagnoses in 1954 and that number has more than doubled.  Nobody will say that most clinicians are using a set of diagnoses so limited that they have the numerical codes memorized so they do not have to keep looking them up.  

A comparable look at the ICD shows that it started out in in 1893 as the International List of Causes of Death (or the Bertillon Classification of Causes of Death).  There were 44, 99, or 161 codes that could be used depending upon the reporting capabilities of the country.  The 161-code version became the ICD and in 1898 the American Public Health Association (APHA) recommended that Canada, Mexico, and the US adopt it and revise it every 10 years based on advancements in medical knowledge.  The current version ICD-11 has 55,000 codes up from the previous version (ICD-10) 14,000 codes.  

Any comparison of numbers of diagnoses is problematic for several reasons.  The authority proposing the classification system is averse to reporting them. That is true whether it is the DSM or the ICD. When I counted them, I provided the methodology and you can replicate it yourself.  With the DSM there are occasional isolated counts close to mine – but no explanations.  With the ICD – things are more complex and estimated range from 10,000 – 15,000 diagnoses that would be recognized as unique.  In the ICD-11 those diagnoses are included with other biomedical terms in the underlying Foundation of the ICD.  The Foundation is technically a semantic database of terms including symptoms and other findings. 

Before getting into how these codings work relative to diagnoses – a brief introduction to ICD coding terminology since it is impossible to separate out what physicians typically consider diagnoses.  In the example below, I have produced a hierarchical tree diagram that is considered the basis for the ICD.  In the example I am following how an episode of recurrent depressive disorder-severe without psychotic features is coded.  The top category is the grouping of all medical disorders into 28 categories.  The next group is all mental, behavioral, and neurodevelopmental disorders grouped into 24 categories.  From there a mood disorder group, depressive disorder group and recurrent depressive disorder group follows.  The final grouping is the variant of 15 recurrent depressive disorder possibilities that we are looking for.  In ICD jargon, that final group is called a leaf code because it is the ultimate result of the hierarchy and it cannot be split any farther.  The branching above that level is called stem codes.   

 

A more interesting comparison is how the diagnostic codes in the rest of medicine have increased.  

Version	Approximate Leaf Codes	Notes	References
ICD-10 (WHO)	~10,607	Base international version	[1]
ICD-10-CM (US)	~71,932	US clinical modification with extensive granularity	[1]
ICD-11-MMS	~14,622	Moderate increase over ICD-10; post coordination expands expressivity	[1]
ICD-11 Foundation	Much larger	Includes 5,500+ rare diseases; serves as semantic knowledge base	[2-3]
1:  Fung KW, Xu J, Bodenreider O. The new International Classification of Diseases 11th edition: a comparative analysis with ICD-10 and ICD-10-CM. J Am Med Inform Assoc. 2020 May 1;27(5):738-746. doi: 10.1093/jamia/ocaa030. PMID: 32364236; PMCID: PMC7309235. 2:  Feinstein JA, Gill PJ, Anderson BR. Preparing for the International Classification of Diseases, 11th Revision (ICD-11) in the US Health Care System. JAMA Health Forum. 2023;4(7):e232253. doi:10.1001/jamahealthforum.2023.2253 3: Chute CG. The rendering of human phenotype and rare diseases in ICD-11. J Inherit Metab Dis. 2018 May;41(3):563-569. doi: 10.1007/s10545-018-0172-5. Epub 2018 Mar 29. PMID: 29600497; PMCID: PMC5959961.

   

The table shows a direct comparison between the ICD-10 and ICD-11.  The conclusion is that there has been a moderate increase in codes.  Leaf codes can undercount and overcount the diagnoses and are not necessarily strict representations of diagnoses.  For example, a code of type 2 diabetes mellitus can generate many additional codes depending on the complications.  The only equivalent in the DSM are the modifier codes.  Medicine can also code symptoms rather than a specific diagnosis – so those codes like “neck pain, cough, constipation, etc) also generate codes that have no DSM equivalent.  There is residual or not-otherwise-specified (NOS) codes in the ICD that meet no diagnostic criteria.  The DSM-5-TR has replaced NOS codes with other specified disorder or unspecified disorder that are probably not much better.  The ICD-11 added complexity codes for severity, histopathology and other features to increase specificity.

The structure of the ICD is relevant to counting diagnoses.  The basic a hierarchical tree structure that can be viewed at the following link.  In this case the diagram illustrates the hierarchy Mental, Behavioral, or Neurodevelopmental disorders (category) -> Mood Disorders (3) -> Bipolar Disorder -> Bipolar Type 1 Disorder (16) -> Bipolar type I disorder, current episode manic, without psychotic symptoms (32) -> Bipolar type I disorder, current episode manic, without psychotic symptoms, with prominent anxiety symptoms (32).  The numbers in parentheses indicate the total branching of the hierarchical tree diagram.  The branching is graphically represented in the center panel.

A comparison of leaf codes in the DSM is possible by estimating leaf codes as 3-5-digit total billable codes.  That would include about 350 leaf code like endpoints and 150 environmental codes for total of about 500.  That is only about 3% of the total ICD-11 codes in the above table – a number made more significant by the fact that the DSM includes diagnoses that the ICD codes in other categories – most notably neurocognitive disorders.   

In conclusion – all of the controversy about the proliferation of diagnoses (or codes) in the DSM as excessive does not match the reality of how diagnoses in general have increased in the rest of medicine. If anything, it seems to be lagging.  It also misses the point why this happens in the first place as it was well put by the American Public Health Association in 1898 – to revise the ICD every 10 years “based on advancements in medical knowledge.”   

 

George Dawson, MD, DFAPA

 

Supplementary 1:  Leaf code approximation:  I counted all of the diagnoses listed in the chapter "Numerical Listing of DSM-5 Diagnoses and Codes (ICD-10-CM)” Total codes listed in that appendix are 760 but it is a mapping of DSM diagnoses onto the ICD-10 and that is not an exact match.  As a result, there are 148 duplicate codes bringing the total down to 612.  The list also contains parent or sub-stem codes such as F79 (Unspecified intellectual disability) that requires an additional digit to become a leaf code.  There are 23 sub-stem codes bringing the total number of leaf codes to 589.

Applying that number to the approximate total leaf codes in the above table yields the following:

589/10,607 = 5.6%

589/14,622 = 4.0%

589/71,932 = 0.8%

Those numbers are consistent with the number of codes and diagnoses in psychiatry are certainly not excessive compared with the rest of medicine and the estimated disease burden (see fig 3).

 

References:

1:  Munk-Jørgensen P, Najarraq Lund M, Bertelsen A. Use of ICD-10 diagnoses in Danish psychiatric hospital-based services in 2001-2007. World Psychiatry. 2010 Oct;9(3):183-4. doi: 10.1002/j.2051-5545.2010.tb00307.x. PMID: 20975866; PMCID: PMC2948730. 

2:  Müssigbrodt H, Michels R, Malchow CP, Dilling H, Munk-Jørgensen P, Bertelsen A. Use of the ICD-10 classification in psychiatry: an international survey. Psychopathology. 2000 Mar-Apr;33(2):94-9. doi: 10.1159/000029127. PMID: 10705253.

3:  Leucht S, van Os J, Jäger M, Davis JM. Prioritization of Psychopathological Symptoms and Clinical Characterization in Psychiatric Diagnoses: A Narrative Review. JAMA Psychiatry. 2024;81(11):1149–1158. doi:10.1001/jamapsychiatry.2024.2652

4:  Mezzich JE, Fabrega H Jr, Coffman GA, Haley R. DSM-III disorders in a large sample of psychiatric patients: frequency and specificity of diagnoses. Am J Psychiatry. 1989 Feb;146(2):212-9. doi: 10.1176/ajp.146.2.212. PMID: 2783540.

5:  Chute CG, Çelik C. Overview of ICD-11 architecture and structure. BMC Med Inform Decis Mak. 2022 May 16;21(Suppl 6):378. doi: 10.1186/s12911-021-01539-1. PMID: 35578335; PMCID: PMC9109286.

6:  Harrison JE, Weber S, Jakob R, Chute CG. ICD-11: an international classification of diseases for the twenty-first century. BMC Med Inform Decis Mak. 2021 Nov 9;21(Suppl 6):206. doi: 10.1186/s12911-021-01534-6. PMID: 34753471; PMCID: PMC8577172.

7:  Quan H, Steinum O, Southern DA, Ghali WA. Coding mechanisms for main condition in ICD-11. BMC Med Inform Decis Mak. 2025 Jul 10;21(Suppl 6):387. doi: 10.1186/s12911-025-03069-6. PMID: 40640794; PMCID: PMC12243148.

Why A Diagnosis Is Not Stigmatizing and What Is...

 

 

The topic came up last week and it happens on a recurrent basis – diagnoses especially psychiatric diagnoses are not good because they are stigmatizing.  I addressed this fairly comprehensively in a post on this blog 10 years ago, but the persistent antipsychiatry rhetoric out there keeps repeating inaccuracies.  Since then there has been a comprehensive academic definition of stigma that makes things clearer.

Before that academic definition the standard dictionary definition was “a stain or reproach, as on one’s reputation” (1).  There is also a medical definition that is used to designate obvious pathognomonic findings: “visible evidence of disease” (2) and a long list of signs that apply.  There are additional definitions that do not apply to the specific situation of how mental illness is stigmatizing. The American Psychiatric Association has a web page on stigma and the adverse effects.  The web page does a good job of breaking it down to the public, personal, and structural levels.  Specific evidence-based interventions are suggested. They typically involve first-hand experience of persons with mental illnesses.

More sophisticated definitions of stigma are available today.  For the purpose of this post I am using one by Andersen, et al (3) that modifies previous work done by Link and Phelan (4).  According to the authors, stigma is a social process that involves “labelling, negative stereotyping, separation, and power asymmetry.” (p. 852).  They state further that stigma is not present unless all these criteria are met – specifically stigma exists “if and only if” all these criteria are present. 

Labelling in this case is defined as “social selection of human differences”.  The authors give an example of associating alcohol use with homelessness and whether it is a matter of “cognitive efficiency” based on personal experience and probabilities. The labelling that occurs is a result of these socially observed differences. Although these labelled associations can be positive, for the definition of stigma only negative associations are relevant for stigma.  That results in the negative stereotyping.

Separation creates a false barrier between the negatively stereotyped and everyone else.   It suggests that there cannot possibly be any overlap between the characteristics of the stereotyped and everyone else.  Earlier in their paper, the authors use the example of obesity, where it is obvious that there are several almost universal stereotypical qualities and overt discrimination. The same thing is true of ageism, where it is often assumed that elderly people are universally frail, cognitively impaired, and have negative personality traits. It is an us versus them mentality that is currently popular in right wing politics in the US.

Power asymmetry is attributed to the fact that is takes social, economic, and political power to label and negatively stereotype. This is inconsistent with the idea that it happens at an individual level and those individuals together can form a power structure. 

The authors cite an example from Link and Phelan: “They notice that mentally ill patients might label clinicians as e.g. “pill pushers” and link them to the stereotypes of being cold, paternalistic, and arrogant. But the clinicians will not, therefore, be a stigmatized group, because this group of patients simply do not possess the sufficient power to “(…) imbue their cognitions about staff with serious discriminatory consequences.”   

The social and pollical dimensions of the pill pusher characterization ignores history and the prevalence factor.  On a historical basis, Osler suggested that medications being used over a century ago were either worthless or cause more harm than good.  At the turn of the century "dope doctors" ran large practices by keeping people addicted to opiates. On the prevalence side, does the number of people with that characterization equal or exceed the number of people with other common important stigmatizing biases like obesity or ageism?  I doubt it. We do see an excessive amount of rhetoric directed at psychiatrists that is largely inaccurate and contrived and it is not without professional, social, and pollical fallout (5,6).  Very few reasonable people seem willing to discuss that.  The other reality that is rarely discussed is the fact that doctors are not powerful and certainly are not trained to use or exert power.  Today they are ordered around by middle level managers with no training in medicine exerting whatever form of administrative power that they choose.

There are much better examples of stigmatizing processes that are obvious but never discussed in today’s world.  I come back to the entertainment industry at the top of the list.  Apart from movie reviews psychiatrists have been curiously silent about this process that has gone on unabated for decades.  To cite a recent obvious example, I would refer anyone to the most recent episode of The Penguin an HBO series.  In season 1 Episode 4, we see one of the protagonists falsely diagnosed with mental illness to keep her from disclosing several homicides committed by her father.  She is placed in a medieval Arkham asylum where the patients are shackled by the neck and treated inhumanely.  She is eventually baited into committing a very violent homicide against another patient who is trying to befriend her.  The psychiatrists there are portrayed as indifferent at best and of course using electroconvulsive therapy as a punishment (there has not been any progress on that issue since One Flew Over the Cuckoo’s nest in 1975).  There may be people who argue these problems may have existed in 18^th and 19^th century asylums – but the problem is this is set in modern times.  The Penguin is driving a 2013 Maserati Quattroporte VI.  This episode plays the familiar stigma as the mentally ill being excessively violent and psychiatrists as agents of the state conspiring against people, using psychiatric treatments as punishments, and not caring at all about individual patients.

Right wing politics is a second source of stigmatization on almost a daily basis.  Trump and affiliated MAGA politicians routinely suggest that mass shooting and gun violence are attributable to mental illness – even though it clearly correlates with firearm availability and density.  In the case of undocumented immigrants, they are triply stigmatized as criminals, mentally ill, and invaders of the country when there is no evidence for it.

A final source is a carry over from my previous post.  Businesses and healthcare companies actively discriminate against mental illness despite parity legislation.  That should be obvious by the lack of resources that people face when trying to find treatment for a severe mental illness. It is easy to find state-of-the-art care and subspeciality care for any other bodily symptom – but not psychiatric care.  Getting an appointment to see a psychiatrist even in large metropolitan areas is often impossible.  Inpatient bed capacity in the United States is somewhere below the bed capacity of developing countries in the world. The majority of people with mental illnesses are not treated.

That is my update on stigma.  The only thing that has changed in the last 10 years is the current spin that a psychiatric diagnosis or treatment is stigma or stigmatizing and of course it is not at all.  As a reminder, a diagnosis is for the information of the patient and other treating professionals, it is confidential, and it is used by people who are professionally obligated to act in the best interest of the patient and incorporate that person's preferences.       

 

George Dawson, MD, DFAPA

 

1:  Random House.  Webster’s College Dictionary.  Random House, New York, 1996: p. 1314.

2:   Steadman’s Medical Dictionary.  The Williams and Wilkins Company, Baltimore1976: p.1338

3:  Andersen MM, Varga S, Folker AP. On the definition of stigma. J Eval Clin Pract. 2022 Oct;28(5):847-853. doi: 10.1111/jep.13684. Epub 2022 Apr 23. PMID: 35462457; PMCID: PMC9790447.

4:  Link BG, Phelan JC. Conceptualizing stigma. Annu Rev Sociol. 2001; 27(1):363‐385.

5:  Perlis RH, Jones DS. High-Impact Medical Journals Reflect Negative Sentiment Toward Psychiatry. NEJM AI. 2023 Dec 11;1(1):AIcs2300066.

6:  Bithell C. Why psychiatry should engage with the media. Advances in psychiatric treatment. 2011 Mar;17(2):82-4.

Photo Credit:

Click on photo to see Wikimedia Commons information about photo and photographer as well as CC license.

The Retired Consultant Redux – A Conversation With Two Internists

In retirement I run into colleagues who are interested in the process and how it is going. I was greeted with a “How is my favorite retired psychiatrist” yesterday. It originated from a highly qualified subspecialist who was immersed in hospital work when I first met him. We talked briefly about his changing roles over the years going from hospital based acute care practice, to an outpatient specialty practice, to his current role of tertiary consultant seeing the most difficult problems in his field. I told him that was the role I miss the most – seeing the most difficult to diagnose and treat cases and being the one to figure out what to do.

It is not an easy life – especially if you are as neurotic as me.  It involves constant research and revision of approaches. It involves close follow up.  It involves sleepless nights and anxiety.  It involves balancing innovation against not wanting to make a mistake.  Sometimes it involves convincing other people to go along with you when they may be reluctant. It also involves tolerating the suffocating routine of excessive documentation and jumping through unnecessary administrative hoops as well as the occasional overt harassment. But in the end – you end up being a physician that both your patients and colleagues can count on and that’s something.

We discussed the nature of treating these populations. He told me he likened his practice to neurology because of the reputation that the level of esoteric diagnoses are not matched by esoteric treatments and often there is not much that you can do. I never understood this degree of pessimism.  I have been confronted with people who told me their last doctor told them: “Look there is nothing more I can do for you.”  And we were able to make some progress.     

Finally – we discussed the 2 year milestone and how many people leave retirement and have to go back into active practice at that point.  He made the observation that this seems to happen across professions where possible – and it seemed to depend on attitudes to retirement and whether you had anything to do.  He did not think retirement would be a problem.  I estimated he had about another 8-10 years of practice left.  I had my usual thoughts about all of the people I knew who never made it to retirement.  I also thought about retirement from physically taxing work and the problems that involves - not the least of which is adjusting caloric intake to prevent excessive weight gain.  

The second conversation was more technical. It was an opinion about gabapentin.  The patient in question was taking it long term for back pain and had a history of back surgeries. More recently she was on diuretics and other medications for atrial fibrillation and congestive heart failure. She was seeing several specialists and they were dutifully getting all of the correct labs but nobody seemed to notice the gradual increase in creatinine to 1.7 and 2.4.  That correlated clinically with increasing somnolence, ataxia, and falls.  After reading the package insert on gabapentin he called me to discuss a dosage adjustment with renal insufficiency.

I recalled a healthy young man I was treating who became acutely confused and ataxic after he was started on simvastatin by a consultant. In psychiatry, this scenario raises suspicions of intoxicants even in a hospital setting. But given the circumstances I decided to also look for a cause of delirium.  The acute labs showed that he had acute renal failure as an idiosyncratic reaction to the statin and he was transferred to medicine to treat the problem.  The acute renal failure led to the accumulation of gabapentin and the delirium and ataxia.

As we discussed the cases, the internist pointed out the difficulty with today’s fragmented medical care.  All of the medication were ordered and the labs were done – but nobody seemed to be paying any attention to how the patient was doing. It reminded him of a quote from one of his mentors George Magnin, MD who used to say to his Medicine residents: “What are you going to do until the doctor gets here?”

That quote struck me as genius both as a motivating factor and the immediate reality of the situation. When you are confronted with a patient who is having a problem – you need to be able to do something about it. That doesn’t mean that you will always know what to do – and if you don’t you at least need to know how to triage the problem so that the patient gets the correct care.  We try to increase the likelihood that will happen by specialization, subspecialization, and settings to match the illnesses with the specialists, but those matches are far from perfect.

I had this experience to illustrate.  I got a call from an emergency medicine physician who was seeing a patient I was treating for bipolar disorder. I knew him and his family very well from years of treatment. The ED doc wanted me to hospitalize him for acute mania but his wife who was with him said he was not manic and she did not want him admitted to a psychiatric unit.  After a brief description of his symptoms I said: “Put him on the phone so I can talk with him.”  Within 30 seconds I could tell he had a fluent aphasia with paraphasic speech errors.  When the ED doc came back on I told him that this was not mania – but most likely an acute stroke syndrome and he was hospitalized on Neurology where the stroke diagnosis was confirmed.

“What are you going to do until the doctor gets here?” – means that doctor.  The one who can diagnose and treat your problem.  That is the one that matters.  In this era of health apps, checklists, self-diagnosis, electronic health records, telemedicine, and so-called artificial intelligence that is still all that matters.

Being that person is hard to attain and hard to walk away from.

 

George Dawson, MD, DFAPA 

Image credit:  Wikimedia Commons: University Hospitial of Zurich,  Creative Commons  CC BY-SA 4.0  https://creativecommons.org/licenses/by-sa/4.0

Additional:  The identities of the physicians were anonymized in this post. I doubt that any physician benefits from being associated with me or this blog.

The Recent Takedowns of Adult ADHD

 

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

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

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

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

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

 

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

 

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

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

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

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

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

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

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

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

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

 

George Dawson, MD, DFAPA

 

References:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

 

 

 

 

An Outstanding Paper on Atrial Fibrillation

 

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

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

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

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

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

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

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

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

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

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

 George Dawson, MD, DFAPA

 

References:

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

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

Supplementary:

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

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

Graphics Credit:

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

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