Attention Deficit Hyperactivity Disorder (ADHD)

Attention Deficit Hyperactivity Disorder (ADHD) is defined as a neuro developmental disorder featuring with symptoms of inattention, overactivity, and impulsivity.

It is a complex, chronic, and heterogenous developmental disorder with typical onset in childhood and known persistence into adulthood. It is the most common neuro-developmental disorder with significant impact on the affected individual’s personal, social, academic, and occupational functioning and development. The levels of impairment are brought about by persistent displays of inattention, dis-organization, and/or hyperactivity-impulsivity.

Aetiology

Research is continually being conducted by determining the cause(s) and risk factors and finding ways to manage and reduce the chances of a person having ADHD. The cause(s) and risk factors for ADHD are unknown, but recent studies link genetic factors with ADHD.

Neurotransmitter Involvement:

It is assumed to result from suboptimal dopamine levels in the synaptic cleft due to over expression of the presynaptic dopamine transporter (DAT).

Familial Origin:

Numerous studies have proven a familial aggregation of ADHD.

Environmental Risk Factors:

Prenatal exposure to alcohol and tobacco, premature birth, low birth weight, critical birth circumstances, and incongruities in parent–child interactions, such as difficulties in feeding the infant, etc. and socioeconomic risk factors (lower socioeconomic strata, single-parent home, maternal depression, antisocial behaviour in the father).

Genetics:

Based on genetic predisposition and psychosocial risks, ADHD leads, among others, to neurocognitive/behavioural problems due to neurobiological dysregulation. These problems manifest mainly in attention and executive functions.

Candidate gene association studies had found dopamine D4 receptor gene (DRD4) and DRD5 variants with consistent associations with ADHD in several meta-analysis studies. There are several genome wide association studies in the early phases of discovery. One recent meta-analysis reported on 12 independent genome-wide significant loci and found that FOXP2 in chromosome 7 correlates with ADHD.

Signs and Symptoms

Already during early infancy, people with ADHD often exhibit signs, such as frequent crying, feeding, and sleeping problems, restless sleep, and excessive unrest.

A child with ADHD might:

• Daydream a lot (being absentminded)

• Forget/lose things a lot (extreme forgetfulness)

• Fidget (can’t focus)

• Talk too much (very talkative)

• Make careless mistakes or take unnecessary risks

• Have a hard time resisting temptation

• Have trouble taking turns

• Have difficulty getting along with others (intra relationship problems)

People with ADHD show deficits in attention intensity and selectivity, in executive inhibitory control (of, e.g., motor action or prepotent responses) and therefore in self-regulation, as well as in memory functions, especially in short-term/working memory. They therefore struggle with continuous vigilance and attention, are easily distracted by internal and/or external stimuli, experience themselves as ‘forgetful’, and express difficulty in self-organizing and performing their daily routines. Possible complications of adult ADHD include poor productivity, poor school performances, employment difficulties, inability to sustain relationships, substance abuse and increased motor vehicle accidents.

Types

In the Diagnostic and Statistical Manual of Mental Disorder (DSM-5), three main nominal subtypes of ADHD are identified which are mainly based on the differential elevation of two dimensions of inattention symptoms and hyperactivity–impulsivity symptoms.

These are:

(i) Predominantly inattentive type (ADHD-I or ADHD-PI) (20-30% of cases) which describes individuals with maladaptive levels of inattention, but not hyperactivity–impulsivity

(ii) Predominantly hyperactive–impulsive type (ADHD-H or ADHD-HI) (15% of cases) which is characterised by maladaptive-e levels of hyperactivity–impulsivity, but not in attention

(iii) Combined type (ADHD-C) (50-75% of cases) which describes individuals who exhibit significant symptoms of both inattention and hyperactivity–impulsivity.

Clinical evaluation and diagnosis

Attention Hyper Activity Disorder (ADHD) is a clinical diagnosis requiring a detailed evaluation of current and previous symptoms and functional impairment. A full family, gestational, and developmental history should be taken.

Evaluation usually starts with a comprehensive clinical interview asking about the youth’s medical, developmental/ behavioural, family, and social histories. Important aspects of the medical history must include infectious or drug exposures in-utero, any pregnancy and delivery complications, medication usage, chronic medical conditions, and previous assessment of hearing and vision abilities.

The clinician should document developmental skills and challenges of the youth (particularly language, motor, and academic) and inquire into educational routine disruptions or significant absences. Due to the strong genetic predisposition of ADHD, family members with ADHD and other neurobehavioral disorders must be determined.

Query on traumatic and adverse life events and disruptions to routine such as home or school moves, and impactful loss or death of loved ones or pets must also be done. A confidential interview with the adolescent may reveal risky health and sexual behaviours. Asking about sleeping and eating habits is important especially if one is considering medication treatments for ADHD.

Differential Diagnosis

A range of medical and psychiatric conditions show symptoms that are also present in primary ADHD. The most important medical conditions which are known to ‘mimic’ ADHD and need to be excluded during the diagnostic process are: epilepsy (especially absence epilepsy), thyroid disorders, sleep disorder, drug interactions, anaemia, and leukodystrophy. The most important psychiatric conditions to be excluded are learning disorders, anxiety disorders, and affective disorders, while an adverse home environment also needs to be excluded.

Attention Hyper-Activity Disorder (ADHD) according to the American Psychiatric Association’s (APA) 5th Diagnostic and Statistical Manual of Mental Disorder (DSM-5) and International Classification of Diseases

(ICD-10/11)

Diagnostic and Statistical Manual of Mental Disorder (DSM-5)

In the DSM-5, the defining symptoms of ADHD are divided into symptoms of inattention (11 symptoms) and hyperactivity/impulsivity (9 symptoms). The former differentiation between subtypes in the DSM-IV ‘proved to be unstable and to ‘depend on the situational context, on informants, or on maturation’, and was therefore replaced by ‘presentations.’ Thus, the DSM-5 distinguishes between different presentations of ADHD: predominantly inattentive (6 or more out of 11 symptoms present), predominantly hyperactive/impulsive (6 or more out of 9 symptoms present), and combined presentation (both criteria fulfilled), as well as a partial remission category.

The DSM-5 defines ADHD in children (younger than age 17 years) as the presence of 6 or more symptoms in either the inattentive or hyperactive and impulsive domains, or both.

Fewer symptoms (e.g., at least five symptoms in either domain) are required to meet the adult diagnostic criteria. The age of symptom onset was modified from ‘before age 7 years’ in DSM-IV to ‘before age 12 years’ in DSM-5 to permit greater flexibility when diagnosing adults.

The International Classification of Diseases (ICD 10 and 11)

ICD-10 classification:

The ICD-10 classification distinguishes between ‘hyperkinetic disorder of childhood’ (with at least 6 symptoms of inattention and 6 symptoms of hyperactivity/impulsivity, (present before the age of 6 years) and ‘hyperkinetic conduct disorder’, a combination of ADHD symptoms and symptoms of oppositional defiant and conduct disorders.

ICD-11 classification:

In the ICD-11 (online release from June 2018, printed release expected 2022), the latter category has been dropped, as has the precise age limit (‘onset during the developmental period, typically early to mid-childhood’). Moreover, the ICD-11 distinguishes 5 ADHD subcategories, which match those of the DSM-5: (i) ADHD combined presentation, (ii) ADHD predominantly inattentive presentation, (iii) ADHD predominantly hyperactive/impulsive presentation and two residual categories, (iv) ADHD other specified and (v) ADHD non specified presentation. For diagnosis, behavioural symptoms need to be outside the limits of normal variation expected for the individual’s age and level of intellectual functioning.

It also updated its diagnostic formulation to bring it into line with DSM-5, uses the term ‘hyperkinetic disorder’ instead of ‘ADHD’ and defines it as ‘a persistent and severe impairment of psychological development’. ‘It is characterised by early onset, a combination of overactive, poorly modulated behaviour with marked inattention and lack of persistent task involvement, and pervasiveness over situations and persistence over time of these behavioural characteristics’.

Pharmacological & Non-pharmacological Management

National Institute for Health and Care Excellence (NICE) guidelines

Age-Specific Needs

According to the NICE guidelines and pharmacological recommendations a distinction should also be made between children under 5 years of age or preschool children, and school children.

• For the younger children (preschool children), parent or career training programs and parent group training programs are always first-line treatments. Medication for children under five years with ADHD should only be given following a second specialist opinion from an ADHD service with expertise in managing ADHD in young children.

• For children over 5 years of age (school children), education and information about the causes and impact of ADHD and advice on parenting strategies should be offered, as well as liaison with schools if consent to do so is provided. Pharmacological management should begin with methylphenidate but to switch to amphetamine if the response is inadequate. They also suggest that children with ADHD are switched to atomoxetine or guanfacine if their response to methylphenidate or amphetamine is poor.

• Adults with ADHD aged 18 years and older (≥ 18 years): pharmacological management is recommend starting with either methylphenidate or lisdexamfetamine. If the response if inadequate the recommendation is to switch to atomoxetine, as there is less evidence for α-2 agonists in adult ADHD. Guanfacine is recommend only for adults following the advice of a tertiary referral centre for attention deficit hyperactivity disorder.

Pharmacological management:

Management options for ADHD in adults include stimulant medications (methylphenidate, dexamphetamine and lisdexamfetamine) and non-stimulant medications (atomoxetine and guanfacine).

Stimulant medications

(1) Methylphenidate:

Methylphenidate is a centrally acting psychostimulant that is subject to the narcotics law. It is approved for the treatment of ADHD in children from 6 years of age, adolescents, and adults, as well as for the treatment of sleep disorders (e.g., excessive daytime sleepiness, narcolepsy). In addition, off-label use of MPH to treat depression is also practiced.

It is available in an immediate release formulation, as well as a choice of long-acting biphasic release preparations, which contain a proportion of the drug as immediate release and a further proportion as modified release methylphenidate, allowing treatment to be tailored to the needs of the individual.

Mechanism of action:

Methylphenidate unfolds its stimulant, indirectly sympathomimetic effects, by inhibiting presynaptic reuptake of dopamine and noradrenaline. Unlike classical reuptake inhibitors, it also induces rapid and significant rises in striatal dopamine efflux, which seems to play a key role for the therapeutic effect of methylphenidate.

It leads to an up regulation of the frontoparietal executive function network and the temporoparietal attentional network, which is associated with improved attention in children with ADHD and better inhibitory control in the prefrontal cortex.

The calming effect of methylphenidate in patients with ADHD is most likely connected with the improvement of dopamine deficiency. It has a high affinity toward the presynaptic dopamine transporter, which is comparable to that of cocaine.

(2) Dexamphetamine:

Is an immediate release stimulant medication which acts both by blocking the reuptake of noradrenaline and dopamine into the pre-synaptic neurone and by increasing the release of noradrenaline and dopamine into the synaptic space. Because of its rapid absorption and short duration of action it has the potential to be abused, and so is contraindicated in patients with a history of drug or alcohol abuse.

(3) Lisdexamfetamine:

Is a long-acting pro-drug formulation of dexamphetamine with a long duration of action (12–14 hours). Lisdexamfetamine is pharmacologically inactive until hydrolysed by the red blood cells to dexamphetamine following oral absorption. This process of hydrolysis is rate limited, significantly reducing the abuse potential of lisdexamfetamine compared to dexamphetamine, even if ingested by other routes, for example intravenously or intranasally.

Side effects:

The common side effects of stimulant medications include anorexia, abdominal pain, and small average increases in heart rate and blood pressure. Patients should be advised to take their stimulant medication in the morning to allow it to have left their system by bedtime, thereby reducing the risk of insomnia as a side effect. However, for some patients, where initial insomnia is a problem because of a ‘racing mind’, addition of an evening dose of an immediate release stimulant may be beneficial.

Non-stimulant medications:

Relative to stimulants, non-stimulant medications have lower responses and effect sizes and thus are typically reserved for patients who respond poorly or have intolerable side-effects to trials of stimulant formulations.

Non-stimulant medications include:

1. The norepinephrine transporter inhibitor, atomoxetine, and

2. The α-2 agonists, guanfacine and clonidine.

Most treatment guidelines deem non-stimulant medications second-line treatments to be considered if treatment with stimulants proves inadequate.

Atomoxetine

Atomoxetine is licensed for the treatment of ADHD in adults and acts by blocking the re-uptake of noradrenaline via the pre-synaptic noradrenaline transporter, thereby enhancing concentrations of noradrenaline in the synaptic space. Atomoxetine takes 2–4 weeks to exert a therapeutic effect and is a useful option where there are concerns regarding risk of misuse or diversion.

It is estimated that 7% of the Caucasian population are poor metabolisers of atomoxetine, resulting in an increase in half-life from 4–21 hours. Poor metabolisers are far more susceptible to side effects which may cause them to discontinue taking it, even at very low doses.

---

Table 1 Dosage recommendation for the most used psychostimulants and other medications in the treatment of children and adolescents with Attention‑Deficit Hyperactivity Disorder (ADHD)

Source: Drechsler R, Brem S, Brandeis D, Grünblatt E, Berger G, Walitza S. ADHD: Current Concepts and Treatments in Children and Adolescents. Neuropediatrics. 2020 Oct;51(5):315-335

---

Table 2: Medications for adult Attention‑Deficit Hyperactivity Disorder (ADHD) – types of formulation

Source: Prakash J, Chatterjee K, Guha S, Srivastava K, Chauhan VS. Adult attention-deficit Hyperactivity disorder: From clinical reality toward conceptual clarity. Ind Psychiatry J. 2021 Jan-Jun;30(1):23-28

---

Management of ADHD and Co-morbidities:

For the management of adult ADHD, the major considerations which need to be addressed are the co-morbidities, which are quite common. In addition, the treatment of ADHD has significant ramifications on the co-morbid illness as well. Medical co-morbidities, hypertension, type II diabetes, obesity, asthma, and migraine are common.

Disorder‑specific approach primarily includes pharmacological intervention. The commonly used medication groups are stimulants with which up to 75% immediate improvement has been noted. These medications are however avoided in patients with co-morbid substance abuse or recent‑onset tics or seizures

Non-Pharmacological Management and Interventions

A growing body of evidence to supports the use of non-pharmacological approaches, particularly in combination with pharmacological treatment.

Non-specialists have an important role in identifying people who they suspect may have ADHD and signposting them to specialist services for diagnosis and treatment.

Alternative Non-Pharmacological Interventions

Cognitive Behavioural Therapy, psychotherapy, mindfulness training, physical activity, yoga, taking nutritional supplements such as: fish oil; zinc; iron; and magnesium and complex carbohydrates (can improve brain function and reduce mood swings) and exercise (improves executive functions).

Literature also reports that some parents consulted a traditional healer/faith healer, either before consulting a medical doctor, and reported that the healer suggested psychiatric referral. In South Africa, there is a lack of child mental health services, with faith healers playing an important role in trying to bridge that gap, as they are generally accessible. Providing mental health education for faith healers may facilitate appropriate and timeous referral as they may be the first point of contact for parents when seeking an understanding of unusual behaviour.

Barriers and misconceptions

Some common parental misconceptions that are present in research from developed and developing countries are: (i) The misconceptions regarding the sugar intake-associated symptoms of ADHD, (ii) use of stimulant leading to addiction, (iii) reliance on punishment to bring behavioural change and (iv) outgrowing ADHD were common in this and other studies.

An American study suggested that black Americans strongly accepted the ADHD ‘sugar’ aetiology. In the study the authors proposed that this may be because of factors such as different cultural thresholds and perception of bad behaviour, beliefs that ADHD is not a medical condition, discrimination, lack of trust of health professionals and economic constraints based on socio-cultural differences.

Policy establishment

Current research regarding ADHD in both children and adults should guide policy makers to, for example, implement effective screening, treatment, and follow-up strategies to prevent complications and ensure fulfilling academic and eventually professional careers. This can be done by adapting curriculum and career paths which require academic and occupational skills that could be compromised by a diagnosis of ADHD.

Prospects in the management of ADHD

The limitations of medication treatment for ADHD highlight the importance of the continued search for new and improved approaches to its management. For example, new compounds are being explored and technology-assisted delivery of standard treatment is being developed.

---

Attention Hyper-Activity Disorder (ADHD) is a common neurological disorder that commonly affects children and adults. The prevalence varies from worldwide and from country to country. There are many variables associated with ADHD such as gender differences, types of presentations, variables in between these and as so on. This condition is managed multimodally with the combination of pharmacological stimulants, such as methylphenidate, amphetamines, and non-stimulants, such as atomoxetine and guanfacine in combination with non-pharmacological interventions such as psychotherapy. New advances are made in the management of this disorder.

---

References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition DSM-5TM. Washington, DC: American Psychiatric Publishing; 2013.

Atwoli L, Owiti P, Manguro G, Ndambuki D. Attention deficit hyperactivity disorder symptom self-report among medical students in Eldoret, Kenya. Afr J Psychiatry (Johannesburg). 2011 Sep;14(4):286-9.

Ayano G, Yohannes K, Abraha M. Epidemiology of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents in Africa: a systematic review and meta-analysis. Ann Gen Psychiatry. 2020 Mar 13;19:21.

Bitsko RH, Claussen AH, Lichstein J, Black LI, Jones SE, Danielson ML, Hoenig JM, Davis Jack SP, Brody DJ, Gyawali S, Maenner MJ, Warner M, Holland KM, Perou R, Crosby AE, Blumberg SJ, Avenevoli S, Kaminski JW, Ghandour RM. Mental Health Surveillance Among Children - United States, 2013-2019. MMWR Suppl. 2022 Feb 25;71(2):1-42.

Cabral MDI, Liu S, Soares N. Attention-deficit/hyperactivity disorder: diagnostic criteria, epidemiology, risk factors and evaluation in youth. Transl Pediatr. 2020 Feb;9(Suppl 1):S104-S113.

Chamakalayil S, Strasser J, Vogel M, Brand S, Walter M, Dürsteler KM. Methylphenidate for Attention-Deficit and Hyperactivity Disorder in Adult Patients With Substance Use Disorders: Good Clinical Practice. Front. Psychiatry. 2021 Jan 26;11:540837

Chinawa JM, Odetunde OI, Obu HA, Chinawa AT, Bakare MO, Ujunwa FA. Attention deficit hyperactivity disorder: a neglected issue in the developing world. Behav Neurol. 2014;2014:694764.

Ching'oma CD, Mkoka DA, Ambikile JS, Iseselo MK. Experiences and challenges of parents caring for children with attention-deficit hyperactivity disorder: A qualitative study in Dar es salaam, Tanzania. PLoS One. 2022 Aug 3;17(8):e0267773.

Dessie M, Techane MA, Tesfaye B, Gebeyehu DA. Elementary school teachers knowledge and attitude towards attention deficit-hyperactivity disorder in Gondar, Ethiopia: a multi-institutional study. Child Adolesc Psychiatry Ment Health. 2021 Apr 7;15(1):16.

Dobrosavljevic M, Solares C, Cortese S, Andershed H, Larsson H. Prevalence of attention-deficit/hyperactivity disorder in older adults: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2020 Nov;118:282-289.

Drechsler R, Brem S, Brandeis D, Grünblatt E, Berger G, Walitza S. ADHD: Current Concepts and Treatments in Children and Adolescents. Neuropediatrics. 2020 Oct;51(5):315-335.

Erskine HE, Baxter AJ, Patton G, Moffitt TE, Patel V, Whiteford HA, Scott JG. The global coverage of prevalence data for mental disorders in children and adolescents. Epidemiol Psychiatr Sci. 2017 Aug;26(4):395-402.

Guan Lim C, Lim-Ashworth NSJ, Fung DSS. Updates in technology-based interventions for attention deficit hyperactivity disorder. Curr Opin Psychiatry. 2020 Nov;33(6):577-585.

Johnson J, Morris S, George S. Attention deficit hyperactivity disorder in adults: what the non-specialist needs to know. Br J Hosp Med (London). 2020 Mar 2;81(3):1-11.

Regnart J, McCartney, J, Truter, I. Drug holiday utilisation in ADHD-diagnosed children and adolescents in South Africa, J Child Adolesc Ment Health. 2014; 26:2,95-107.

Vrba K, Vogel, W, de Vries, PJ ()Management of ADHD in children and adolescents: clinical audit in a South African setting, J Child Adolesc Ment Health. 2016; 28:1,1-19.

Munasur-Naidoo AP, Truter I. Review of adult attention-deficit/hyperactivity disorder in South Africa. Expert Rev Pharmacoecon Outcomes Res. 2017 Aug;17(4):343-353.

Njuwa KF, Simo LP, Ntani LL, Forchin AN, Parviel C, Tianyi Tianyi FL, Nsah B, Agbor VN. Factors associated with symptoms of attention deficit hyperactivity disorder among medical students in Cameroon: a web-based cross-sectional study. BMJ Open. 2020 May 7;10(5):e037297.

Pila-Nemutandani RG, Meyer A. Behaviour planning and problem solving deficiencies in children with symptoms of attention deficit hyperactivity disorder from the Balobedu culture, Limpopo province, South Africa. J Child Adolesc Ment Health. 2016 Jul;28(2):109-21.

Posner J, Polanczyk GV, Sonuga-Barke E. Attention-deficit hyperactivity disorder. Lancet. 2020 Feb 8;395(10222):450-462.

Prakash J, Chatterjee K, Guha S, Srivastava K, Chauhan VS. Adult attention-deficit Hyperactivity disorder: From clinical reality toward conceptual clarity. Ind Psychiatry J. 2021 Jan-Jun;30(1):23-28.

Rajcumar NR, Paruk S. Knowledge and misconceptions of parents of children with attention-deficit hyperactivity disorder at a hospital in South Africa. S Afr Fam Pract. 2020;62(1):a5124.

Shrestha M, Lautenschleger J, Soares N. Non-pharmacologic management of attention-deficit/hyperactivity disorder in children and adolescents: a review. Transl Pediatr. 2020 Feb;9(Suppl 1):S114-S124.

Tsujii N, Usami M, Naya N, Tsuji T, Mishima H, Horie J, Fujiwara M, Iida J. Efficacy and Safety of Medication for Attention-Deficit Hyperactivity Disorder in Children and Adolescents with Common Comorbidities: A Systematic Review. Neurol Ther. 2021 Dec;10(2):499-522.

Van Wijk CH, Meintjes WAJ. Adult attention-deficit/hyperactivity disorder prevalence among commercial divers in South Africa. Diving Hyperb Med. 2020 Jun 30;50(2):164-167.

Websites

Centres for Disease Control and Prevention (CDC). 2022, August 8. What is ADHD? Available at: https://www.cdc.gov/ncbddd/adhd/facts.html#SignsSymptoms, accessed: 13 September 2022

Centres for Disease Control and Prevention (CDC). 2022, August 9. Attention-Deficit / Hyperactivity Disorder, Data and Statistics About ADHD. Available at: https://www.cdc.gov/ncbddd/adhd/data.html, accessed: 13 September 2022

Centres for Disease Control and Prevention (CDC). 2022, August 9. Attention-Deficit / Hyperactivity Disorder, What parents can expect in behaviour therapy. Infographic. https://www.cdc.gov/ncbddd/adhd/infographics/what-parents-expect.html accessed: 13 September 2022

Centres for Disease Control and Prevention (CDC). 2022, August 9. Attention-Deficit / Hyperactivity Disorder, What Parents Learn When Trained in Behavior Therapy. Infographic. https://www.cdc.gov/ncbddd/adhd/infographics/behavior-therapy-parents.html accessed: 13 September 2022

Centres for Disease Control and Prevention (CDC). 2022, August 8. What is ADHD? Available at: https://www.cdc.gov/ncbddd/adhd/facts.html#SignsSymptoms, accessed: 13 September 2022

Centres for Disease Control and Prevention (CDC). 2022, August 9. Attention-Deficit / Hyperactivity Disorder,, Data and Statistics About ADHD. Available at: https://www.cdc.gov/ncbddd/adhd/data.html, accessed: 13 September 2022

World Health Organization. 1993. The ICD-10 Classification of Mental and Behavioural Disorders. www. who.int/entity/classifications/icd/en/bluebook.pdf. Accessed: 20 September 2022

Compiler: Dr. Liesl Brown, B Square Synergy Consultants.

#ADHD #AttentionDeficitHyperactivityDisorder #BlogPost #CPD #ClinicalCarePlatformBlog