Attention deficit is what I consider to be one of the “sacred cows” of psychiatry along with Borderline Personality (discussed in another post). They are both misunderstood, overdiagnosed, and poorly validated especially in adults. Here I will focus on underpublicized, underappreciated, and forgotten clinical studies that have yet to put a damper on professional and public enthusiasm for this diagnosis.

The first element to consider in examining ADD, is the faulty interchangeability of ADD and ADHD. The “H” in ADHD is misleading when considering a diagnosis because it puts emphasis on the hyperactivity element rather than the cognitive impairment. I am following Nassir Ghaemi’s suggestion of calling this ADD instead of ADHD, because of the ambiguity in the term “hyperactive” (see Clinical Psychopharmacology – Principles and Practice 2019 p. 543).

The ambiguity around the term “hyperactivity” in the DSM criteria overlaps significantly with childhood hypomanic, manic, and mixed symptoms as well as childhood cyclothymia, and lacks any specificity in clinical studies for “ADHD.” Is it meant to suggest increased energy? If so, this points more toward mania, or being fidgety coming from inattention, which can be a result of being required to sit for prolonged periods in school.

Following Ghaemi: “an initial common error is to diagnose “ADHD” in children based mainly on “hyperactivity” without asking whether this reflects increased energy, in which case the diagnosis should be mania instead, not “ADHD.” One way to avoid this common error is a refusal to abide the unscientific insistence of the DSM on using the term “ADHD” and instead to use the term ADD so as to put the emphasis on the diagnosis where the science shows it to be: in cognitive impairment not increased energy.” (Clinical Psychopharmacology – Principles and Practice 2019, p 544).

Since inattention due to a delay in cortical maturation, rather than hyperactivity, is the core of attention deficit; ADD should be used, rather than ADHD. 

Therefore in this blog I will refer to ADHD in quotes (“ADHD”) or just ADD. 

Before jumping into the details of ADD, it is important to review the concepts of a diagnostic hierarchy and diagnostic validators so that ADD is put in its proper place. These concepts apply to adults and children for any diagnostic consideration.

In a diagnostic hierarchy, used in the rest of medicine, polysymptomatic conditions such as mood disorders supersede all lower tier diagnoses because they can be explained by a higher tier diagnosis that envelopes its symptoms. 

1. Mood Disorders – Bipolar – Mixed – Unipolar
2. Psychotic Disorders – Schizoaffective – Schizophrenia
3. Anxiety Disorders, PTSD, OCD
4. Other – Personality Disorders (borderline), ADHD, Eating disorders, etc. 

                                                  PG Surtees, RE Kendell. Br J Psych, 1979, 135:438-443

A lower tier diagnosis should not be elevated above a higher tier diagnosis, nor should it be considered “comorbid.” The DSM uses a non-scientific threshold system where if a number of criteria is reached, another diagnosis can be added and called “comorbid.”

In a traditional medical model this would the equivalent of diagnosing a “fever disorder,” a “cough disorder,” a “chest discomfort disorder,” a “tiredness disorder,” and a “sputum disorder” in addition to Pneumonia, simply because each reached a threshold count, when only one diagnosis is necessary. 

In a classic 1970 publication, the famous epidemiologist Alvan R. Feinstein, MD, defined comorbidity in relation to a specific index condition as “any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study.” (Feinstein AR. J Chronic Dis 1970; 23:455-68).

In Feinstein’s formulation, the implication was that a completely different and independent disease occurred at the same time as another disease. These two diseases co-occurred, more often than not, randomly. The DSM does not follow this formulation, and therefore, does not operate within a medical model.  

True comorbidity is the random, simultaneous occurrence of two independent, unrelated diseases and not simply the overlap of symptoms as allowed by the DSM, e.g., “ADHD” is not comorbid with any mood illness i.e., Bipolar, nor is it comorbid with “GAD” (to be discussed in another post).

Diagnostic Validators such as family history/genetics, symptoms, biological markers (sorely lacking in psychiatry), and least important –  response to treatment – are not required by the DSM, only symptoms.

Again, the rest of medicine does not rely solely on symptoms for a diagnosis and for some medical conditions there are no symptoms, i.e., hypertension and cancer in the early stages. The classic 1970 paper by Robins and Guze is clearly in a traditional medical model with its lineage traced back to the 19th century prescient ideas of Kahlbaum and Kraepelin, where course, outcome, and family history are the most important of the validators in psychiatry. (Robins E. Guze S. Establishment of Diagnostic Validity in Psychiatric Illness: Its application to Schizophrenia. AJP, Vol. 126, issue 7, January 1970 pp. 983-987).

Are Stimulants better than psychosocial interventions for ADD?                                             

The NIMH 1999 Multimodal Treatment of children with ADHD (MTA) study is the longest randomized trial of amphetamines in childhood ADD, with a one-year randomized period and two more years of non-randomized outcomes. 

• The primary finding contrary to the emphasis of its authors and experts is that amphetamines are not more effective than behavioral interventions for functional outcomes, i.e., academic achievement, oppositional/aggressive behaviors, social skills, or parent/child relations. 
• Amphetamines were more effective for the symptoms of ADD, i.e., kids were observed to be more attentive and less agitated. 
• Amphetamines were shown to shorten height by .75 inches in one year.
• Substance abuse was not decreased with amphetamine treatment and was increased in two-year outcomes. 
• If behavioral management is used in treatment, medications can be avoided entirely in nearly half of children for the long term. 

(Jensen P.S., et.al. (1999) Multimodal Treatment of children with ADHD (MTA) Arc. Gen. Psyc. 56, 1073-1086). (from Clinical Psychopharmacology – Principals and Practice 2019 p.340)  

Summary:   

• ADD is characterized by the core feature of inattention. 
• Increased energy, i.e., “hyperactivity” is not a feature of the syndrome. 
• There is no paradoxical effect of stimulants: they simply improve attention which improves behavior.
• Childhood ADD is a developmental delay, not a permanent disease.
• Treatment for ADD can be given for a short duration, if at all, in childhood and need not be continued into adulthood in most persons. 

(Clinical Psychopharmacology – Principles and Practice 2019 p.546)

Is ADD a disease of the brain?

In a prospective study of children with ADD using MRI and PET scans, with matched controls, children with ADD showed evidence of brain abnormalities (decreased blood flow and reduced cortical thickness) in some regions (dorsolateral prefrontal and ventromedial frontal cortex). There were abnormalities present around ages 7-8 but then normalized by about ages 11-12.

In sum, there was a 2–3-year delay in cortical thickness maturation, especially in the prefrontal cortex, in ADD children vs. matched non-ADD controls. The straightforward interpretation of this research is that ADD is a developmental delay, not a permanent disease. It represents normal childhood delayed by a few years. (As every parent knows, some kids have delayed growth spurts.)

 (Shaw P. et. al. 2007, Attention-deficit/hyperactivity disorder in children is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences, 104, 19649.) from Clinical Psychopharmacology – Principals and Practice 2019, p 549.  

Misdiagnosis in children

In a study of children with an index diagnosis of MDD (major depressive disorder), 27% had received a prior diagnosis of “ADHD;” and in a group with a primary diagnosis of Bipolar, 32% had received a prior diagnosis of “ADHD” primarily because the original “ADHD” diagnosis was made without the use of the diagnostic hierarchy explained above. Both of these groups likely received treatment with stimulants for the supposed “ADHD.”  

(JK Chilakamarri, M Filkowski, SN Ghaemi, Misdiagnosis of bipolar disorder in children and adolescents: a comparison with ADHD and major depressive disorder. Ann Clin Psychiatry. 2011;23:25-29.

In my experience seeing children and adolescents in hospital emergency departments who present predominantly with suicidal ideation and various forms of self-harm, a significant number are taking stimulant meds, often in conjunction with an SSRI. Virtually none of these children have been screened for the common mixed depressive states which involve physical and mental agitation, i.e., psychomotor agitation, leading to inattention and so-called “hyperactivity.” Mood lability is also frequently reported by the parental figure.  Their family histories are often positive for some type of depression (mild or severe), psychiatric hospitalizations, suicides or attempts, or outright Bipolar Illness – none of which points to a diagnosis of “ADHD.” The meds are prescribed by both PCPs and psychiatric prescribers. They may have had a Connors rating scale or PHQ-9 (if anything) but I have never heard that the Parent Mood Disorders Questionnaire (MDQ) for Adolescents was used. The prescriptions for stimulants seem to be almost reflexive without taking the time to assess the presence of the higher tier diagnoses in the Diagnostic Hierarchy. Most psychiatric experts, even if they don’t know about or believe a diagnostic hierarchy is necessary, recommend that ADD should not be diagnosed in the presence of a mood disorder, depression, mixed or manic and that the mood disorder should be treated first and fully before consideration of ADD. If a first degree relative has been diagnosed with a Bipolar Illness there is an 85% heritability for the child, and thus ADHD should not be considered. 

For Clinical Practice: When diagnosing ADD in children, 

• Do not focus on hyperactivity.

• Rather the central clinical diagnostic feature should be inattention.
• The diagnosis shouldn’t be made in the setting of other conditions that cause inattention like anxiety, depression, mania/ hypomania, or mixed symptoms, and psychosis. 

• The most common symptom in children that produces inattention is anxiety.

• Anxiety itself is often a prodrome to other conditions (such as mood and psychotic illness) which are often worsened by amphetamines.

• SSRI medications are often used for anxiety, but they can worsen mood and psychotic conditions.

• They should be used for no longer than a year due to problems with serotonin withdrawal.
• The long-term effects of SSRI meds on sexual development if continued throughout adolescence are not known. 

• For children, don’t routinely diagnose ADD with inattention and certainly not for “hyperactivity.” 

• Consider anxiety and other syndromes and minimize the dosage and duration of medication treatment as much as possible.

• Remember well designed studies show ADD is a temporary, developmental delay in cortical maturation that normalizes in the late teen years and medications may not be necessary and certainly not long term into adulthood.  

(from Clinical Psychopharmacology – Principles and Practice 2019)

Studies that did not use a Diagnostic Hierarchy

The Kessler epidemiological study below found that when adult ADD symptoms were reassessed using telephone interviews, 45.7% of childhood ADD had persistence into adulthood. However, they also found that those who had inattention also had eleven times greater anxiety disorders which were not ruled out as a cause of inattention, so it is likely the presumed persistence of “ADHD” symptoms would be a lot less. 

In keeping with the medical model of a diagnostic hierarchy, the inattention may be due to anxiety symptoms (not disorder), and these symptoms may likely be due to a major mood disorder i.e., (hypo)mania, mixed, or unipolar depression which would be at the top of the diagnostic hierarchy and not “comorbid” with ADD for an adult or a child.   Kessler RD.et. al. The Structure and Diagnosis of Adult ADHD: An Analysis of Expanded Symptom Criteria from the Adult ADHD Clinical Diagnostic Scale (ACDS) Arch Gen Psychiatry. 2010 Nov; 67(11): 1168–1178.

Same author, Kessler’s prior retrospective study:

• 36% of those with childhood “ADHD” met current criteria for adult “ADHD”. 

•  Childhood “ADHD” is associated with bipolar disorder in 37% diagnosed, and 57.6% in any mood disorder (i.e., significant overlap of symptoms which is not helpful diagnostically in the absence of family history and course).

•  Adult “ADHD” is associated with bipolar disorder in 45% of respondents, and with any mood disorder in 84.1% of respondents.  (Again, significant overlap of symptoms does not mean two separate “disorders.”)

RC Kessler et al, Biological Psychiatry, 2005, 57: 1442-1452

According to this study, for children diagnosed with “ADHD,” up to nearly 60% met criteria for either bipolar or another mood disorder. In a diagnostic hierarchy, the poly symptomatic mood disorder would supersede “ADHD” because the mood disorder can better explain the symptoms of supposed “ADHD,” and would not be considered “comorbid.” Unfortunately, this happens all too often in children since the diagnosis of a bipolar diagnosis is avoided and the treatment given is usually a stimulant. Even for doctors who are not familiar with the hierarchy, most experts advise that a mood disorder i.e., bipolar, mixed or unipolar should be treated first and as fully as possible before treating suspected ADD, the symptoms of which may disappear with treatment of the mood disorder since they may not be comorbid. In adults, nearly 85% also had either a bipolar or unipolar diagnosis, and the same thinking as above would apply. 

What did we Learn from the Brazilian study in JAMA of 2016?

Course of Illness – the most important Diagnostic Validator 

A unique prospective study of just over 5,249 youths (followed from age 11 to 18) used a diagnostic hierarchy (unlike previous studies) to rule out “ADHD” if a mood disorder was present.

They assessed the presence of ADD, i.e., “ADHD”

•  At age 11, 8.9% of kids were diagnosed with ADD and by age 18, 12.2% were diagnosed with ADD i.e., an “adult” group.
•  However, when those 18 yr. olds were screened for mood illness (bipolar or unipolar), the rate of ADD fell to 6.3%. 
•  By age 18, only 17.2% of 11 yr. olds above with ADD continued to manifest symptoms into adulthood i.e., 82.8% did not – it resolved.  
• At age 18, only 12.6% (of the above 12.2% “adult” group who had not been diagnosed at age 11) had ADD in childhood and were newly diagnosed at age 18, so 87.4% did not have ADD in childhood which contradicts the DSM.

Because the DSM defines adult “ADHD” as being present in childhood, this study shows that most of the kids had normative intentional impairment, but not “ADHD.” The findings in the Brazilian study can tell us inconvenient and currently unaccepted truths about the course of an illness that can only be ascertained prospectively and not respectospectively or cross sectionally. Simply put, many children thought to have ADD really have something else; and in the vast majority of children who meet the DSM criteria for just ADD and no other condition, do not meet the criteria by age 18. This study is the best available for documenting the course of an illness, one of the two most important diagnostic validators not included in the DSM.  

(A Caye et al, Attention-Deficit/Hyperactivity Disorder Trajectories from Childhood to  Young Adulthood,. JAMA Psychiatry, 2016, vol. 73: p.705-712)

The 33-year Prospective Study of 8-year-olds.

(Advanced Diagnosis Course 2021 – psychiatryletter.net)

I think you need a sentence here to frame these results so as people read them , they can filter into comprehension and not just float around in the brain looking for a place to land…?

The research findings and conclusions below were not highlighted or included in many standard textbooks or training programs for psychiatrists, nor were these findings used to change any “ADHD” criteria in DSM-5, leading to the incorrect assumption that “ADHD” is more prevalent in children and adults than currently believed by many doctors and the general public. 

• ADD persisted in 22%, i.e., not in almost 80% which is consistent with studies before 2000. 
• ADD was diagnosed in 5% of adults in a control group, who did NOT have childhood ADHD.
• Antisocial personality: 14% ADD vs 0% controls (who did not have ADD in childhood).
• Substance abuse common: 14% ADHD vs 5% (who did not have ADD in childhood).  
• Mood disorders: 9% vs 6%
• Anxiety disorders: 13% vs 9%

So, the “ADHD” rates are really due to the other conditions and not true ADD since the kids did not have “ADHD” in childhood and were followed for 33 years. 

Conclusions:* 

• Almost 80% of childhood “ADHD” does not persist into adulthood. 
• Epidemiological prevalence of “adult ADHD” is consistent with normal variations of cognitive function. 
• The clearest adult outcome of “ADHD” is antisocial personality.
• Mood and anxiety disorders are one-third more common outcomes in adulthood for children with “ADHD.”

*RG Klein et al, Archives General Psychiatry, Dec 2012, 69: 1295-1303 

Consider non-stimulant treatments:

• In 2020, the FDA approved use of a game-based digital device (EndeavorRx) https://www.endeavorrx.com/ for the treatment of ADD in youths aged 8-12 years. This approval by the FDA marks the first of its kind and paves the way for future digital treatments for ADD as well as other mental health conditions.

• Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study: This study found that 20-30 mg/day of saffron extract was as effective at reducing both inattentive and hyperactive/impulsive symptoms of ADHD as was 20-30 mg/day of methylphenidate. Throughout this 6-week study there were no significant differences on either the Parent- or Teacher-ADHD-RS-IV for symptoms of ADHD between saffron and methylphenidate and side effects occurred less often. These data offer promise of a potentially cost-effective, widely-available, non-divertible treatment for ADHD. Baziar S et al. J Child Adolesc Psychopharmacol 2019;29(3):1-8   https://www.liebertpub.com/doi/10.1089/cap.2018.0146 

• The most empirically validated nonpharmacological modality for disruptive and externalizing behaviors is the Behaviorally Oriented Parent Management Training program to help the child develop self-regulation.
• Social effectiveness therapy for children (SET-C) is a cognitive behavioral therapy (CBT) for children/adolescents that involves psychoeducation, social skills training, and exposure exercises.
• Equazen® Pro – essential fatty acids, designated by Thorne company as a medical food to address cognitive issues.