Evidence Based Summary of the ADHD International Consensus Statement

DIAGNOSIS AND PREVALENCE OF ADHD

ADHD is usually diagnosed between the ages of 6 to 12 years, with a rate of approximately 5.9% of school-aged children. [Willcutt et al. 2012]

Although ADHD diagnoses have become more common, this may reflect our increased understanding and recognition of the disorder.

• There appear to be no significant differences between developing and developed nations. [Polanczyk et al. 2014]
• ADHD is more common in males with a 2:1 ratio over females [Willcutt et al. 2012]
• ADHD diagnosis is more common in Black Americans [Cénat et al. 2021]

ADHD in females presents differently. Read about gender differences in the presentation of ADHD in females. 

A diagnosis requires neuroimaging, neurological testing, and a clinical interview with a parent and/or patient.

During an interview, an ADHD diagnosis is based on the following standard evidence-based criteria [Crunelle et al 2018]; [NICE 2018]; [Kooij et al 2019]:

1. Inappropriate levels of hyperactive-impulsive and/or inattentive symptoms for at least 6 months
2. Symptoms occur in different environments such as home and school
3. Symptoms that impair living
4. Symptoms or impairments first occurred in early to mid-childhood
5. No other relevant disorder is present although the presence of other psychiatric disorders does not rule out an ADHD diagnosis

Detailed review on Diagnosis of ADHD. 

AETIOLOGY OF ADHD

The aetiology of ADHD has genetic and environmental components; these components have also ucheen shown to interact with each other, whereby different genotypes influence susceptibility to different environmental risks. [Faraone et al. 2015]

In addition, DNA studies have shown that genetic and environmental effects are shared with other psychiatric disorders (e.g., schizophrenia, bipolar disorder, depression, and ASD).

Genetic Causes: 

• Several known genetic risk variants, each with a small effect, suggest that ADHD is polygenic in most cases. Therefore, it has been predicted that there is a threshold for symptoms in the general population. [Demontis et al. 2019]
• However, several key risk genes are directly associated with the development of ADHD, although these still require validation in genome-wide studies.

Environmental Toxins:

• Toxins such as organophosphate pesticides [Bouchard et al. 2010], lead [Nilsen and Tulve 2020], and artificial food dyes [Nigg et al. 2012] are also linked to an increased likelihood of ADHD.
• Furthermore, the maternal use of valproate and paracetamol have also been linked to an increased risk. [Chen et al 2019]; [Christensen et al 2019]

Nutritional deficiencies:

• Nutritional deficiencies have also been identified in youths with ADHD.
• This includes lower serum ferritin but not iron [Wang et al. 2017], omega-3 PUFAs [Hawkey and Nigg 2014], and vitamin D levels compared to non-ADHD youths. [Sucksdorff et al. 2021]

Maternal influences:

• Prenatal exposure to alcohol abuse [Wetherill et al. 2018] or smoking [Dong et al. 2018] have been consistently associated with the development of ADHD.
• In addition, mothers who are hypertensive [Maher et al. 2018], obese [Jenabi et al. 2019], or had hyperthyroidism [Ge et al. 2020] were also more likely to have children with ADHD.
• Lower maternal Vit D levels were associated with an approximately 50% greater likelihood of ADHD in their children.

Environmental influences: 

• Deprivation, stress, infection, poverty and trauma are associated with an increased risk of ADHD.

COMORBIDITIES IN ADHD

Patients with ADHD are at a higher risk of developing several different types of non-psychiatric medical issues. A Swedish national database study showed that adults with ADHD were 4 times more likely to have a prescription for a somatic disorder and 15 times more likely to have a prescription for a psychiatric disorder. [Zhang et al. 2020]

Obesity:

• Patients with ADHD have a 3-fold greater risk of developing obesity compared with their non-ADHD siblings. [Chen et al. 2018]
• It has also been shown that unmedicated patients are more likely to be overweight or obese compared to medicated patients. [Cortese et al. 2016]

Diabetes:

• Patients with ADHD are more likely to develop type 2 diabetes. [Chen et al. 2018]
• Interestingly, maternal type 2 diabetes is also associated with an increased risk of their offspring developing ADHD. [Zeng et al. 2020]

Autoimmune Disorders:

• There is a 50% increase in the risk of developing asthma, allergic rhinitis, or atopic dermatitis.
• Ankylosing spondylitis, ulcerative colitis, and autoimmune thyroid disease are found at higher rates.
• Migraine and ADHD are strongly associated in a bidirectional manner.
• Conversely, maternal asthma is also associated with an increased risk of their offspring developing ADHD. [Liu et al. 2019]

Sleep Disorders

• Sleep-disordered breathing and deficits in sleep-onset latency and sleep efficiency have also been observed in patients with ADHD. [Lugo et al. 2020]

Eye abnormalities:

• ADHD is significantly associated with several different eye abnormalities, including amblyopia, astigmatism, and heterotropia. [Ho et al. 2020]

IMPACT ON QUALITY OF LIFE

Research shows that children with ADHD have impaired social and school functioning. For instance, moderate impairments have been observed for sharing, cooperation, and reciprocation and socialising with peers and social information processing (i.e., social cues and social problem solving). [Ros and Graziano 2018]

• However, as the child grows into an adult, their physical and emotional functioning show significant deficits. [Lee et al. 2016]
• Emotional dysregulation, such as reactivity to novel or stressful events, is recognised as a significant deficit compared to normally developed controls. [Beheshti et al. 2020]

Patients with ADHD are also significantly more likely to experience an accidental injury or minor traumatic brain injury.

Commonly reported injuries include burns (70% increase in risk), vehicular crashes (23 to 50% increase in risk), and sport-related concussions (3x more likely). [Chang et al 2014]; [Vaa 2014]; [Nelson et al 2016]; [Yeh et al 2020]

• Patients with ADHD have a small increase in their risk of premature death (due to unintentional injuries). However, this risk does increase if there is a comorbid substance use disorder or another psychiatric disorder. [Dalsgaard et al. 2015]
• Attempted suicide and suicidal ideation are also more commonly found in patients with ADHD compared with normally developed people. [Septier et al.; 2019]
• It is also important to note that the rate of completed suicide is 4 times greater in patients with ADHD and 10 times greater in patients with ADHD and a comorbid psychiatric disorder. [Fitzgerald et al. 2019]

TREATMENT OF ADHD

Evidence-based guidelines recommend therapy with stimulants such as amphetamines, methylphenidate, extended-release guanfacine, atomoxetine, or amphetamine derivatives (dextroamphetamine, lisdexamfetamine, and mixed amphetamine salts). [Crunelle et al 2018]; [NICE 2018]; [Kooij et al 2019]

• Methylphenidate strongly reduces adult ADHD symptoms. [Faraone et al. 2004]
• Dexmethylphenidate strongly reduces youth ADHD symptoms. [Maneeton et al. 2015]
• Amphetamine derivatives moderately reduce ADHD symptoms. [Castells et al. 2011]
• Atomoxetine moderately reduces ADHD symptoms. [Cheng et al. 2007]

Of note, treatment with methylphenidate and lisdexamfetamine has been shown to result in small-to-moderate reductions in emotional dysregulation, whereas atomoxetine only resulted in small reductions. [Lenzi et al. 2018]

The treatments with the best benefit-to-risk ratios were methylphenidate for children and adolescents and amphetamines for adults. [Cortese et al. 2018]

Medication treatment for ADHD did not affect brain structure. Medication treatment for ADHD made the brains of youth with ADHD function similar to those without ADHD in brain areas involved in the control of cognition, which is typically disrupted in ADHD.

Side Effects: 

• Methylphenidate is associated with an increased risk of insomnia and anorexia.
• No significant increase in cardiovascular risk with methylphenidate in children and adolescents compared to atomoxetine or placebo.
• A Swedish registry study of over 23,000 adolescents and young adults treated with methylphenidate for ADHD found no evidence for an association between psychosis and methylphenidate treatment. A year after initiation of methylphenidate treatment, the incidence of psychotic events was 36% lower in those with a history of psychosis and 18% lower in those without a history of psychosis relative to the period immediately before the beginning of treatment. [Hollis et al., 2019]
• Methylphenidate does not increase the risk of suicide
• Stimulants moderately reduced total sleep time delayed the onset of sleep, and slightly-to-moderately decreased sleep efficiency (7 studies, 155 children)
• Children treated with stimulants may show delays in expected height gains averaging two centimetres over one or two years. These sometimes attenuate over time and often reverse when treatment is stopped.
• Atomoxetine has a higher discontinuation rate due to poor tolerability in adults.

Non -Medication Treatments: 

In addition, recent discussions on the detrimental impact of a “Western pattern” diet have increased parent interest in making lifestyle-related changes to treat ADHD symptoms (i.e., to restrict sugar, additives, preservatives, and oligoantigenics). Oligoantigenic foods are foods that could potentially provoke an allergic response.

This is particularly prevalent when pharmacotherapy has proven unsatisfactory or is unacceptable.

• Supplements (omega-3 PUFAs) and dietary modifications (reducing artificial food dyes) have been suggested to be associated with small reductions in ADHD symptoms. [Nigg et al 2012]; [Puri and Martins 2014]
• Exercise has also been suggested; however, effects are limited to reductions in anxiety/depression symptoms rather than hyperactivity/impulsivity or inattention symptoms. [Zang et al. 2019]
• Behavioural treatments are also recommended, although these differ depending on the age of the patient.
• For children with ADHD, the parents are trained to improve how they interact with their children. [Rimestad et al. 2019] For adolescents and adults, therapy focuses on specific domains such as organisational skills, social behaviours, or developing practical skills.
• There is insufficient evidence for meditation or neurofeedback.

Overall, medication treatments are more effective than non-medication treatments for ADHD; however, non-medication treatments are helpful as augmentation for residual symptoms after medication treatment.

CONCLUSION

Our understanding of ADHD has increased over the last decade.

While further research is needed to develop optimal treatments, appropriate diagnosis and management of ADHD can improve the lives of the many people who suffer from the disorder and its complications.