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Adult ADHD — the ‘enemy at the gates’

Epidemiology

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterised by the three core symptoms of inattention, hyperactivity and impulsivity. It has been well established as a diagnosis in children and adolescents for many years but has only recently begun to be recognised as also being a prevalent disorder in the adult population.

In the US, the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) reports prevalence rates of 3-7 per cent for school-age children. In the UK, the classification system generally used is the International Classification of Diseases (ICD-10). This provides more stringent criteria for diagnosis of ‘hyperkinetic disorder’, which is the equivalent of the more severe DSM-5 subtype of ‘combined type ADHD’.  It follows that, because the ICD-10 diagnosis is more restrictive, prevalence rates in the UK are lower and are estimated at around 1.5 per cent. However, if DSM-5 criteria are applied to the UK population, similar prevalence rates to the US are seen, as evidenced by a large study by Ford et al in 2003,   in which 3.62 per cent of boys and 0.85 per cent of girls between the ages of five-to-15 years had ADHD in a survey of 10,000 children.

A recent large-scale epidemiological study in the US estimated the prevalence of adult ADHD at 4.4 per cent. While it had previously been widely accepted that the symptoms of ADHD improved with age, current literature suggests that clinically-significant symptoms persist into adulthood in a large proportion of patients, although reported persistence rates vary widely from 4-66 per cent. 

In addition, there is significant evidence that persistence of ADHD symptoms causes significant morbidity and functional impairment in adults. Although childhood ADHD is far more prevalent in boys than girls, clinically-significant symptoms appear to be equal in men and women. There is no data to suggest that persistence rates differ according to gender and thus the lack of an observable difference between men and women may represent a referral bias.

In Ireland, there is limited epidemiological data on psychiatric disorders in children but rates of ADHD appear to be similar to other Western countries.

In Irish adults, the data is limited. One study found the prevalence of adult ADHD to be as high as 24 per cent in the outpatient psychiatric setting and in another study, it was estimated at 13 per cent in those with substance misuse disorders.

People with ADHD show a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development.

Inattention: Six or more symptoms of inattention for children up to age 16, or five or more for adolescents aged 17 and older and adults; symptoms of inattention have been present for at least six months and they are inappropriate for developmental level.

Often fails to give close attention to details or makes careless mistakes in schoolwork, at work, or with other activities.

Often has trouble holding attention on tasks or play activities.

Often does not seem to listen when spoken to directly.

Often does not follow through on instructions and fails to finish schoolwork, chores, or duties in the workplace (eg, loses focus, side-tracked).

Often has trouble organising tasks and activities.

Often avoids, dislikes, or is reluctant to do tasks that require mental effort over a long period of time (such as schoolwork or homework). Often loses things necessary for tasks and activities (eg, school materials, pencils, books, tools, wallets, keys, paperwork, eyeglasses, mobile telephones).

Is often easily distracted.

Is often forgetful in daily activities.

Hyperactivity and impulsivity: Six or more symptoms of hyperactivity-impulsivity for children up to age 16 years, or five or more for adolescents aged 17 and older and adults; symptoms of hyperactivity-impulsivity have been present for at least six months to an extent that is disruptive and inappropriate for the person’s developmental level:

Often fidgets with or taps hands or feet, or squirms in seat.

Often leaves seat in situations when remaining seated is expected.

Often runs about or climbs in situations where it is not appropriate (adolescents or adults may be limited to feeling restless).

Often unable to play or take part in leisure activities quietly.

Is often ‘on the go’, acting as if  ‘driven by a motor’.

Often talks excessively.

Often blurts out an answer before a question has been completed.

Often has trouble waiting his/her turn. Often interrupts or intrudes on others (eg, butts into conversations or games).

In addition, the following conditions must be met:

Several inattentive or hyperactive-impulsive symptoms were present before age 12 years.

Several symptoms are present in two or more settings, (eg, at home, school or work; with friends or relatives; in other activities).

There is clear evidence that the symptoms interfere with, or reduce the quality of, social, school, or work functioning.

The symptoms do not happen only during the course of schizophrenia or another psychotic disorder. The symptoms are not better explained by another mental disorder (eg, mood disorder, anxiety disorder, dissociative disorder, or a personality disorder.

Aetiology

We have no definitive answers at present regarding the pathogenesis of ADHD and it is likely that the aetiology is complex and multifactorial. The current neurotransmitter hypothesis suggests dysregulation of dopamine and noradrenaline, in particular dopaminergic hypofunction in the frontal lobes and basal ganglia. 

This is based on the observation that the psychostimulant medications, which are highly effective in treating symptoms of ADHD, alter concentrations of these neurotransmitters. Our knowledge of the mechanism of action of stimulant medications is increasing and it is believed that they act by increasing concentrations of dopamine and noradrenaline in the neuronal synapse.

One of the major ways in which they achieve this is via blockade of the dopamine transporter on the pre-synaptic membrane, thus preventing re-uptake of dopamine into the neuron. They act at various areas in the brain, the most important of which in ADHD appear to be the dorsolateral prefrontal cortex and striatum. Other neurotransmitters that may also play a role, possibly via a modulating effect on the catecholamines, include histamine, acetylcholine, serotonin and alpha-agonists, but further research in this area is needed.

There is strong evidence that a significant genetic component exists in relation to the aetiology of ADHD. Family, twin and adoption studies all support a genetic basis. Heritability is estimated at 0.75- 0.90 which is higher than for any other psychiatric disorder. No single gene of large effect has been identified but several candidate genes have been implicated, including the dopamine transporter type 1 (DAT1) gene and the D2 and D4 dopamine receptor genes.

Neuroimaging studies have greatly added to our knowledge of ADHD. The use of functional MRI, PET and SPECT scans is a fast-developing and complex field.

Interpretation of the vast number of studies, each showing structural and functional differences between ADHD cases and controls, is far from straightforward. A meta-analysis by Dickstein et al in 2006 concluded that the most consistent neuroimaging findings in ADHD are deficits in neural activity within fronto-striatal and fronto-parietal circuits.

Environmental influences may play a role in the aetiology of ADHD. Although no specific causal relationships have been shown and the association may be a result of the condition itself, several environmental factors are associated with increased risk for development of ADHD. These include prenatal exposure to nicotine; antenatal maternal stress and anxiety; institutionalisation and deprivation in early childhood; maltreatment; child sexual abuse; and various adverse family factors, such as parental psychopathology; parental conflict; paternal criminality; low socioeconomic class; large family size; and foster care placement.

Studies have also demonstrated that certain food additives (eg, artificial colours, sodium benzoate) are associated with increased ADHD symptoms in children. A paper currently in print indicates that ADHD is actually a risk factor for most of the above factors (personal correspondence).

In summary, the pathogenesis of ADHD involves several CNS neurotransmitters, most notably noradrenaline and dopamine. It involves many areas of the brain but the frontal cortex and the corpus striatum appear to be most frequently implicated. The underlying aetiology is complex and multifactorial and likely involves significant gene-environment interaction — the stress-diathesis model.

Based on the types of symptoms, three kinds (presentations) of ADHD can occur:

Combined presentation: If enough symptoms of both criteria inattention and hyperactivity-impulsivity were present for the past six months.

Predominantly inattentive presentation: If enough symptoms of inattention, but not hyperactivity-impulsivity, were present for the past six months.

Predominantly hyperactive-impulsive presentation: If enough symptoms of hyperactivity-impulsivity but not inattention were present for the past six months.

Because symptoms can change over time, the presentation may change over time as well.

Assessment and diagnosis

Diagnosis of ADHD in adults, like in children, is a clinical diagnosis and a comprehensive clinical interview remains the cornerstone of assessment. Diagnostic criteria used, as in other psychiatric disorders, are dependent upon the DSM-5 and ICD-10 criteria, which are broadly similar, excepting that the ICD-10 is more restrictive in not allowing for a diagnosis of the predominantly inattentive subtype. The DSM-5 criteria are outlined in the panel featured on this page.

These criteria are tailored towards diagnosing childhood ADHD. There is debate about their validity in the adult population presentation and it has been suggested that criteria specific for adults are needed. Wender et al developed the Utah criteria for this purpose. These criteria recognise developmental differences in adult symptoms and take into account symptoms commonly seen in adult ADHD but not included in the DSM-5 criteria, such as mood instability, quick temper, disorganisation and emotional over-reactivity. However, in a review of the various diagnostic criteria, McGough et al reported that the Wender Utah criteria fail to identify patients with the predominately inattentive subtype and may also exclude some patients because of the presence of comorbid conditions, such as major depression.

They conclude that clinicians should be flexible in their use of the current ADHD criteria and that additional research is needed in the area to develop adult-specific criteria. In the meantime, however, a variety of adult-specific tests, including the DIVA 2.0, the Conners’ Adult ADHD Rating Scales (CAARS) (described below) and the DSM-5 and ICD-10 diagnostic criteria are the best available diagnostic guides.

The following steps in the diagnosis of ADHD are adapted from recommendations from Weiss and Murray, 2003.

Assess symptoms of ADHD in the past six months. Current symptoms as defined by the DSM-5 are symptoms that have been present for at least six months. Clinicians can use rating scales to aid with diagnosis. These are discussed further below.

Establish a childhood history. As per the DSM-5 and ICD-10 criteria, symptoms must have been present in childhood. Both DSM-IV and ICD-10 require that symptoms be present before the age of seven years. However, studies reported that these criteria were too stringent regarding the age of onset and excluded a significant proportion of patients. The age of onset was subsequently increased to 12 in DSM-5.

Assess functional impairment in various settings including home, work, school and relationships. As per the criteria, there must be clear evidence that symptoms cause functional impairment and must be present in at least two settings.

Obtain developmental history, including prenatal, childhood and school years. Adults may have significant difficulty recalling childhood ADHD symptoms accurately and obviously a collateral history will be required here. Again, rating scales may be beneficial in gathering this information. In addition, useful information can be obtained from school reports/records and should be sought where possible.

Rule out other psychiatric disorders or establish comorbid diagnoses. ADHD symptoms overlap with symptoms of many other psychiatric disorders and it is important to consider several differential diagnoses, including mood and anxiety disorders, personality disorders and substance abuse. To complicate matters further, ADHD is a highly comorbid condition and many of the above disorders may be co-existent with ADHD. This is discussed further below.

Obtain family psychiatric history. ADHD is a highly heritable condition and a family history of ADHD, albeit sometimes previously undiagnosed, is often present. In addition, enquire about a family history of specific learning disability, dyslexia, dyspraxia, autism spectrum disorder, tics, OCD, attention/behaviour problems and criminal activity. The family history should include information on all first-degree relatives. 

Rule out an organic cause for symptoms by full physical examination. Exclude head injury, neurological problems, thyroid dysfunction and substance abuse.

There are various rating scales that can be useful in screening for and assisting with a diagnosis of adult ADHD. These include:

DIVA 2.0 is currently considered the best diagnostic instrument for adult ADHD and is free to download from www.divacenter.eu.

CAARS. There are two versions, one for self-report and the other for observer ratings.

Adult Self-Report Inventory-4 (ASRI-4) and Adult Inventory-4 (for informants).

Brown Attention Deficit Disorder Scales (BADDS) (self-report).

Copeland Symptom Checklist for Attention Deficit Disorders — Adult Version.

Adult ADHD Self-Report Scales (ASRS)  (free to download at www.hcp.med.harvard.edu/ncs/asrs.php).

Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADS).

Other aids to diagnosis include computerised tests, such as the Conners’ Continuous Performance Test and various neuropsychological tests, eg, assessing executive functions or response inhibition. However, although these may contribute to one’s overall assessment, neither is particularly sensitive nor specific for diagnosis of ADHD. It must be emphasised that although there are many aids to diagnosis available, ADHD diagnosis is ultimately based on a thorough history and clinical interview.

Comorbidities

ADHD displays high levels of comorbid conditions in both children and adults. Estimates of comorbidity in adults with ADHD are as high as 89 per cent, with one family study reporting that 56 per cent of patients had at least two comorbid diagnoses. One of the commonest comorbid conditions appears to be substance use disorders (SUD), with prevalence estimates ranging from 12-50 per cent.

A recent prevalence study in Ireland found the occurrence of ADHD among patients with SUD to be 13 per cent. This Irish study is part of a large ongoing multinational ‘International ADHD in Substance Use Disorders Prevalence (IASP) study’ and data from this study, recently published, is similar to Irish findings, with a reported ADHD prevalence of 13.9 per cent in patients with SUD.

Other comorbidities commonly found in adults with ADHD include personality disorders, especially emotionally unstable and antisocial personality disorders; depressive disorders; bipolar disorder, especially bipolar II disorder; and anxiety disorders.

It can be challenging to distinguish between comorbid disorders and conditions that should be considered as differential diagnoses, as there can be significant symptom overlap, but a careful clinical history should allow differentiation. Screening for comorbidities is important, as they may require their own treatment, they may influence treatment outcome in ADHD or they may reveal a contraindication to stimulant or even non-stimulant medication. 

There is evidence that effective treatment of ADHD symptoms in children also reduces symptoms of comorbid disorders and possibly reduces subsequent risk of SUD in later life, but further long-term research is needed in this area.

Treatment

Treatment of adult ADHD, as with other psychiatric disorders, should follow the biopsychosocial model. Drug treatment is recommended by the UK’s National Institute for Clinical Excellence (NICE) guidelines as being the first-line treatment for adults (unless the patient’s preference is otherwise) but should always be part of a comprehensive programme that addresses psychological, behavioural and educational or occupational needs.

Pharmacotherapy

There are several medications used in the treatment of ADHD in adults, including:

Stimulant medications: Methylphenidate and dexamphetamine

Non-stimulant medications: Atomoxetine, bupropion hydrochloride, tricyclic antidepressants, clonidine, guanfacine and modafinil, among others.

Stimulants

Medication for adults with ADHD should only be commenced by a mental health specialist and if a decision has been made to commence medication, methylphenidate should normally be tried first.

Methylphenidate is available in different pharmaceutical formulations — short-acting (brand names Ritalin and Medikinet); intermediate-acting (brand name Ritalin SR); and long-acting (brand names Ritalin LA, Concerta XL, Equasym XL, Medikinet XL).

The long-acting preparations are ideally preferred, as they allow once-daily dosing in children and less frequent dosing in adults. Of note, although methylphenidate hydrochloride is licensed for use in adults in the US, it is not yet licensed for adult ADHD in the UK or Ireland. At present, Concerta XL is the only methylphenidate preparation available in this country that has information on administration to adults in its summary of product characteristics, which reports that “in adolescents whose symptoms persist into adulthood and who have shown clear benefit from treatment, it may be appropriate to continue treatment into adulthood. However, starting treatment with Concerta XL in adults is not appropriate”. Numerous studies have shown methylphenidate, in different formulations, to be effective in improving ADHD symptoms in adults and off-license use is considered appropriate with informed consent. The doses of methylphenidate in adults range from 45-100mg daily, with the latter being the maximum dose allowed by the British Association of Psychopharmacology (BAP) and NICE guidelines.

Dexamphetamine is another common stimulant medication and should be considered in adults who do not tolerate or respond to methylphenidate. It is also available in different preparations regarding duration of action.

Like methylphenidate, it does not have UK marketing authorisation for adult ADHD.

Side-effects of stimulants are dose-dependent and are generally mild-to-moderate in most patients. Common side-effects include insomnia; decreased appetite; weight loss; nausea; headache; elevated blood pressure and pulse; abdominal pain; tics; irritability; and mood lability. Many of these adverse effects occur early in treatment and improve over time. Rare adverse effects include hepatotoxicity; seizures; psychosis; mania; and suicidality. Long-term studies of adverse effects in adults are scarce but the safety reviews reported an association between the use of methylphenidate and sudden death. According to the NICE guidelines, however, the evidence is inconclusive.

Contraindications to stimulant treatment include severe depression; suicidality; anorexia nervosa; psychosis; uncontrolled bipolar disorder; and various medical conditions, including hyperthyroidism; cardiovascular and cerebrovascular disease; pheochromocytoma; and vasculitis. 

When prescribing stimulants, it is important to consider the potential for diversion and drug misuse. As outlined earlier, ADHD is a common, comorbid condition in adults with substance use disorders and in these patients, extreme caution is needed in using stimulants and atomoxetine, which does not have diversionary potential, should be considered as a first-line treatment. 

Atomoxetine

Atomoxetine is a non-stimulant medication that inhibits the noradrenaline transporter, thus inhibiting reuptake of noradrenaline. It is a suitable first-line alternative in patients in whom:

Stimulants are contra-indicated.

Who have not tolerated or responded to stimulants.

Stimulant diversion is a potential risk.

Tics or stereotypies are a problem.

Sleep is not a problem.

Atomoxetine has had a license for continuation of use in adults who were commenced on it as children for some time. It recently received authorisation to expand its indication for initiation of treatment of ADHD in adults, where pre-existing symptoms during childhood have been confirmed by a third party. This makes it the only medication that is currently licensed for use in newly-diagnosed adult ADHD.

Advantages of atomoxetine include once-daily dosing, lack of abuse potential, less rebound effects and a mild anti-anxiety effect.

However, its onset of action is slower and it can take several weeks for maximum treatment effect to be achieved. Atomoxetine is best given as a single dose in the morning, unless poorly tolerated due to nausea, when it can be given morning and early evening (no later than 5-6pm, as it causes total insomnia in most who take it at night-time).

The side-effect profile is similar to that of the stimulants. The most common side-effects include nausea; reduced appetite; insomnia; raised blood pressure and pulse; sweating; and dysuria. In addition, there are reports of agitation; irritability; suicidal thinking and self-harming behaviour, especially in the first few weeks of treatment; and patients should be advised of and observed for these. Other potential side-effects include sexual dysfunction and dysmenorrhoea.

Patients should also be warned of potential liver damage, although this is rare. As with the stimulants, safety reviews have reported cases of sudden death in patients taking atomoxetine; again, the NICE guidelines state that the evidence is inconclusive.

Other agents

Bupropion is an antidepressant that acts via inhibition of dopamine and noradrenaline reuptake. It is licensed as an aid to smoking cessation and is currently not licensed for patients aged under 18 years or for the treatment of ADHD. There is some evidence that it reduces the core symptoms of ADHD and may be of particular use in patients with comorbid depression.

Tricyclic antidepressants (TCA) are often mentioned as second-line options in the treatment of ADHD. However, according to the NICE guidelines, there is no conclusive evidence that TCAs are of value in the treatment of the symptoms of ADHD.

Clonidine is an alpha-2 noradrenergic agonist that is licensed for the treatment of hypertension, migraine and menopausal flushing. Unlicensed uses of clonidine include the treatment of tics and Tourette’s syndrome and it may be of use in patients with ADHD and comorbid tics.

Guanfacine is another alpha-2 agonist that has shown some efficacy in treatment of ADHD symptoms in children and adults.

Modafinil is a centrally-acting sympathomimetic that promotes wakefulness and is indicated in the treatment of narcolepsy. It has been shown to be effective in treating ADHD symptoms in children but there is no data available on its use in adults.

Pre-medication work-up and monitoring

Prior to commencing medication in adults with ADHD, a full medical work-up should be completed in order to aid choice of agent and look for contraindications. The NICE guidelines recommend the following:

Full mental health and social assessment.

Full history and physical examination, including:

Assessment of history of exercise syncope, undue breathlessness and other cardiovascular symptoms.

Heart rate and blood pressure (plotted on a centile chart).

Weight.

Family history of cardiac disease and examination of the cardiovascular system.

An ECG if there is past medical or family history of serious cardiac disease, a history of sudden death in young family members or abnormal findings on cardiac examination.

Risk assessment for substance misuse and drug diversion.

As the condition is a neurodevelopmental disorder, a history of dyslexia, dyspraxia, autism spectrum disorder, bipolar affective disorder and seasonal affective disorder should be sought in first- and second-degree relatives.

In relation to monitoring of patients taking stimulants or atomoxetine, adult patients should have blood pressure, pulse and weight measured every six months. Quality of sleep should be enquired about, as with all treatments for ADHD.

While height is an important consideration in children, it is generally unnecessary in adults who will already have achieved full height. If there is significant weight loss with drug treatment, BMI should be measured and if weight loss is persistent, medication may need to be changed. The presence of side-effects should be sought, including the less obvious anti-cholinergic side-effects of urinary retention and constipation, and co-existing conditions reviewed. The need for continued drug treatment should be reviewed at least annually and current guidelines of the British Association of Psychopharmacology and the NICE guidelines also recommend annual (at least) ECG and blood pressure checks, in addition to bi-annual specialist review. The latter poses quite a challenge in Ireland but it is hoped to change that in the next year by increasing access to training in diagnosis and treatment in this country.

Psychosocial interventions

Psychotherapeutic intervention can help address problems such as poor time management, organisational skills, problem-solving skills, temper outbursts, relationship difficulties, etc. The evidence for psychological treatments in adult ADHD is sparse; however, general clinical consensus seems to be that cognitive behavioural therapy (CBT) has a therapeutic role.

Group-based treatments have the added advantage of providing the opportunity to meet other patients and share experiences, but may not suit everybody. Marital problems are commonly reported by adults with ADHD and psychoeducation of spouses and families is important. Life coaches and ADHD coaching are now available and these are very helpful in managing the organisational and time-management skills of the patient. CBT is useful for dealing with the anxiety, depression and addictions that have developed due to the impulsive nature of the ADHD-afflicted.

Conclusion

Adult ADHD is a significant public health issue due to its high prevalence in the general population and its resultant morbidities of anxiety disorders, depression, substance misuse and personality disorder. Recent research by Ginsberg et al has shown that the treatment of ADHD in prison populations is associated with substantial non-recidivism rates.

Treatment of ADHD in adults is associated with lower rates of anxiety, as the medication is itself anxiolytic. Psychoeducation around adult ADHD and in adults who have a long history of ADHD is often very helpful in allowing the sufferer to understand why they have made certain life decisions and how their lives evolved as they did — a useful starting point in psychotherapy.

While there is a certain reluctance among primary care physicians to prescribe psychostimulants, this can be overcome by explaining that these agents are not stimulants so much as relaxing and anxiolytic in ADHD sufferers. Diversion of psychostimulant medications has not proven to be a significant problem in Ireland, especially among the adult patient population.

For the future, the real challenges clinically are in treating those with ADHD and additional or co-morbid neurodevelopmental disorders, such as autism spectrum and neurological disorders, where sensory perceptual issues arise often and can be made much worse by the use of dopamine-promoting agents. However, the neurochemistry of these conditions is becoming clearer and revealing how the role of dopamine and serotonin changes with the developing brain.

Many self-help and support groups have been growing in Ireland and the demand for treatment is reflected in the development of ‘ADHD clinics’ in two major private hospital services, in addition to the continued development of the first independent adult ADHD clinic in Naas, Co Kildare, which is now expanding into Northern Ireland at the request of the families of ADHD sufferers.

The UK Adult ADHD Network and the UK ADHD Partnership are providing training courses in diagnosis and treatment of adult ADHD and one of the authors is a member of both of these and is engaged in research both in Ireland and in the UK in collaboration with universities there.

Adult ADHD is a real and immediate risk to our young people and a continuing problem for the adult sufferer. It is time for Irish psychiatry to start learning about ‘the enemy at the gates’. The gates are now opening.

References available on request

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