ADHD Diagnosis and ADHD Treatment | Research Review 

This research review is based on a journal article published in Lancet by Jonathan Posner, Guilherme Planczyk, and Edmund Sonuga-Barke. I thank them for doing the heavy lifting in advancing our comprehensive knowledge on improving the lives of our patients with ADHD. 

Article Reference - DOI: 10.1016/S0140-6736(19)33004-1 

Article Title: Attention-deficit hyperactivity disorder

Journal: Lancet

Year Original Article Published: 2021

Research review written by: Sir Norman Melancon, MD 

*Disclaimer: This article is not medical advice, this content is considered media. The information and advice published or made available through this blog is not intended to replace the services of a physician, nor does it constitute a doctor-patient relationship. Information on this blog is provided for informational purposes only and is not a substitute for professional medical advice. You should not use the information on this blog for diagnosing or treating a medical or health condition. You should consult a physician in all matters relating to your health, and particularly in respect to any symptoms that may require diagnosis or medical attention. Any action on your part in response to the information provided in this blog is at the reader's discretion. The information provided on this blog is not intended to cause harm to any individual or entity. The publisher of this blog is not responsible for any specific health needs that may require medical supervision and is not liable for any damages or negative consequences from treatments carried out based on the information provided in this blog.

What exactly is ADHD and what is the history of ADHD diagnosis?

We have really been redefining and reformulating our hypothesis of what adhd is and how it works only over the last 50 years. Over time, we have moved towards a more accurate idea of this syndrome, but it’s important to remember that our understanding is a hypothesis getting closer and closer to true understanding. In the 1970s and 80s, some suggested that ADHD was a product of “developed” nations' highly competitive culture. A very different understanding than our current evidence which points to a lifelong difference in neurobiological structure in the brain.

A large meta-analysis looking at diagnostic rates across 35 countries in 6 continents estimated a prevalence of 5% in children and adolescents with no prevalence differences between North America and other continents and no change over a time span of 1985 to 2012 (Polanczyk, et al). For adults, estimated prevalence is 2.5% with some longitudinal studies showing a decline of symptoms over time (Simon, et al.)

In the most recent edition in the psychiatric diagnostic manual, the age of onset of symptoms for adhd was extended from age 7 to age 12 to allow for more flexibility in assessing adults for the first time. Trying to ask an adult about their symptoms prior to age 7 presents many challenges. The diagnostic language was also changed in order to communicate that sub-types like impulsive, hyperactive, and inattentive can change over time as patients age and enter into new life experiences like work and parenthood. Current diagnostic criteria

Although our diagnostic criteria in the field make it seem like there is a firm boundary between those who have the disorder and those who don’t, my experience and common sense say otherwise. The current criteria for diagnosing ADHD are based on an estimated hypothesis of what number of symptoms and severity of symptoms we (the medical research community) think warrant an intervention. Especially, in this case, it provides somewhat of an educated guess on who should get access to medications who should not. 

How do you get ADHD?

ADHD is highly heritable which means that a large component is driven by genetics and passed down from parents. Some estimates range inheritance to be between 70-80% which makes ADHD nearly as genetically driven and heritable as someone’s height (Faraone, et al). 

Beyond genetics, the environmental contributions to development of ADHD can only be clarified as correlations rather than causations because it’s hard to create a study designed to introduce a harm to children and then measure who gets ADHD and who does not. Prenatal correlations not confounded by genetics would be premature birth, gestational diabetes, and low birthweight (Nigg, et al). Childhood exposures that have some correlation with ADHD symptoms severity include exposure to artificial food coloring and flavoring, environmental pollutants, and agricultural pesticides (Nigg, et al). 

Some of the brain differences in people with ADHD include abnormal maturation of the prefrontal cortex with some studies showing a 2-3 years delay in reaching peak cortical thickness for much of the cerebrum compared to others without ADHD during youth (Shaw, et al). Other imaging studies have shown a pattern of delayed maturation of a circuit in the brain called the default mode network which, in part, is responsible for mind-wandering and introspection, thus accounting for some of the poor regulation of attentional energy in children and adults with adhd (Sonuga, et al). 

Another observation is that patients with ADHD have reduced volumes in brain areas that are key players in the dopamine system such as reduced brain volumes of the nucleus accumbens which impacts reward, impulsivity, and energy levels (Hoogman, et al).

What is the experience of having ADHD?

There is a wide variation in the experience of ADHD symptoms across individuals. Some people may display a pervasive pattern of impairment in executive functioning and cognitive skills across domains and others will have significant impairment in some domains while others remain within normal averages. 

Oftentimes, patients will describe having increased difficulty with repetitive uninteresting tasks and respond differently than peers to incentives and punishments. Patients will notice that the cognitive deficits will actually change noticeably depending on the setting or the relationship. Research has shown that ADHD patients compared to peers will suffer many more errors in their work if the task is too slow and uninteresting or if the tasks are too rapid and repetitive (Metin, et al). 

Is treatment for ADHD symptoms effective?

We know that the impact of ADHD goes beyond the classroom and workplace with impacts on social relationships, bonding, accidents, emergencies, lower economic productivity, and a high co-occurrence with other mental health disorders. 

We certainly know from research and clinical experience that, in the short-term, psychostimulant medications are extremely effective and relatively rapid in ameliorating key symptoms of ADHD: reduced procrastination, increased time on task, reduced distractibility, improved impulse control and improved delayed gratification. However, we don’t have enough data and experience to truly know the long term impact of treatment on important life factors such as accidents, work performance, school performance, and social connection. 

For patients under age 6, guidelines generally recommend starting with parent coaching/training and behavioral management for the child in mild to moderate ADHD cases. Medications at this age are typically reserved for severe cases that have failed other non-pharmacologic interventions. 

Medications are typically categorized into two large categories: stimulants and non-stimulant medications. I will review medications in more detail in a separate article. Within the stimulant category, there are two main divisions: the methylphenidate class (common examples are ritalin, concerta, focalin) and the amphetamine class (common examples are adderall, dexedrine, and vyvanse). 

Most of these medications come in an instant release (IR) form with a shorter time of efficacy and an extended release (ER) form with a longer time of efficacy that can be dosed once daily. Selection of medication may also be based on whether or not a patient may prefer/need tablet, capsule, liquid, or transdermal patch. 

The standard non-stimulant medications are atomoxetine, guanfacine, and clonidine. These are less commonly used because they are much less effective. They typically come into play if patients have a reason that they cannot take stimulants (side effects, active heart issues, substance use history, unstable psychosis or bipolar disorder, institutional settings). Additionally, they have been useful in my practice in some patients who only have a partial response to stimulants and need an adjuvant agent to help improve overall efficacy of the treatment plan. 

Methylphenidates work by increasing the amount of norepinephrine and dopamine in the nerve synapse by blocking presynaptic norepinephrine and dopamine transporters. Amphetamines have this same mechanism and, additionally, increase the presynaptic production of dopamine leading to even higher levels of dopamine in the synapse. 

One of main long-term risks to be aware of in treatment for children and adolescents is the potential impact on growth trajectory. Long term stimulant use has some evidence of a reduction in adulthood height of 1-3cm (Greenhill, et al.) I try to mitigate these risks by having patients take weekends off medication as well as vacations, holidays, and school breaks. Most of the time, the benefit of treatment outweighs the risk of shorter adulthood height but this should be a shared treatment decision. 

Regarding heart health, registry based studies looking at large data sets have been reassuring that there is no relationship between long term stimulant use and heart disease. However, it’s important to monitor blood pressure and do a good history and family history because there is a higher risk of heart issues in patients that may have certain cardiomyopathies, such as hypertrophic obstructive cardiomyopathy

Does therapy work for treating ADHD?

There was an MTA study in 1999 looking at school aged children between 7-10 years old for kids treated with methylphenidate alone or methylphenidate plus psychosocial interventions. The ADHD specific symptoms had the same level of improvement in both groups. However, other important factors like family relationships, social interactions, and overall academic performance were superior in the group that combined psychological and behavioral techniques at home and at school with medication (MTA cooperative). 

Exercise, meditation, and dietary treatments have shown some slight benefit but there isn’t much evidence yet produced about long-term reduction in ADHD symptoms.

Research in the area of non-pharmacological interventions is minimal and we need much more development to determine rigorously which interventions yield clinically successful improvements, especially in adults. It is likely that we will begin to apply specific interventions like executive skills coaching and behavioral impulse control techniques more scientifically as we break down the heterogeneous disorder of ADHD into specific subtypes that respond to interventions uniquely. 

References:

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; 164: 942–48.

Polanczyk GV, Willcutt EG, Salum GA, Kieling C, Rohde LA. ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis. Int J Epidemiol 2014; 43: 434–42.

Simon V, Czobor P, Bálint S, Mészáros Á, Bitter I. Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis. Br J Psychiatry 2009; 194: 204–11.

Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006; 45: 1284–93.

The MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Multimodal treatment study of children with ADHD. Arch General Psychiatry 1999; 56: 1073–86.

Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry 2005; 57:1313–23. 

Nigg JT, Knottnerus GM, Martel MM, et al. Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control. Biol Psychiatry 2008; 63: 325–31.

Metin B, Roeyers H, Wiersema JR, van der Meere J, Sonuga-Barke E. A meta-analytic study of event rate effects on go/no-go performance in attention-deficit/hyperactivity disorder. Biol Psychiatry 2012; 72: 990–96.

Shaw P, Eckstrand K, Sharp W, et al. Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proc Natl Acad Sci USA 2007; 104: 19649–54.

Sonuga-Barke EJ, Castellanos FX. Spontaneous attentional fluctuations in impaired states and pathological conditions: a neurobiological hypothesis. Neurosci Biobehav Rev 2007; 31: 977–86. 

Hoogman M, Bralten J, Hibar DP, et al. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis. Lancet Psychiatry 2017; 4: 310–19.

Previous
Previous

Bupropion | Medication Guide