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.