European Consensus Statement on Diagnosis and Treatment of Adult ADHD: The European Network Adult ADHD

Sandra JJ Kooij; Susanne Bejerot; Andrew Blackwell; Herve Caci; Miquel Casas-Brugué; Pieter J Carpentier; Dan Edvinsson; John Fayyad; Karin Foeken; Michael Fitzgerald; Veronique Gaillac; Ylva Ginsberg; Chantal Henry; Johanna Krause; Michael B Lensing; Iris Manor; Helmut Niederhofer; Carlos Nunes-Filipe; Martin D Ohlmeier; Pierre Oswald; Stefano Pallanti; Artemios Pehlivanidis; Josep A Ramos-Quiroga; Maria Rastam; Doris Ryffel-Rawak; Steven Stes; Philip Asherson

Disclosures

BMC Psychiatry. 2010;10(69) 

In This Article

Background

ADHD is among the most common psychiatric disorders in childhood with well established diagnostic and treatment services available throughout most of Europe. Until recently, the disorder was considered by many to resolve during adolescence and young adulthood with little or no continued impact in adult life,[1] although descriptions of the adult condition appeared in the psychiatric literature from 1976 onwards.[2] However current evidence indicates that in the majority of cases ADHD persists into adult life where it is associated with a range of clinical and psychosocial impairments. Numerous follow-up studies of children with ADHD show that the disorder persists during adolescence and adulthood in around two-thirds of individuals[3–11] either as the full blown disorder or in 'partial remission' with persistence of some symptoms associated with continued clinical and psychosocial impairments. In the meta-analysis of these data from Faraone and colleagues it was concluded that about 15% retain the full diagnosis by age 25 years, with a further 50% in partial remission,[12] indicating that around two-thirds of children with ADHD continue to have impairing levels of ADHD symptoms as adults.

Although in some cases the symptoms of ADHD may appear to diminish during adolescence, this may not be the case relative to controls and does not mean that functioning is unimpaired. In a follow-up study of 119 boys of 19 years of age with childhood onset ADHD, symptom levels seemed to be lower than in childhood but 90% still did not function well.[13] Importantly, although symptoms levels appear to reduce as people grow older there are parallel changes among control groups; so that significant case-control differences are retained.[14]

In a study from the World Health Organisation Mental Health Survey, it was found that childhood predictors of adult ADHD included the combined subtype of ADHD in childhood, symptom severity, the presence of comorbid depression, high rates of other comorbidities, social adversity and parental psychopathology;[3] while Biederman had previously reported family history of ADHD, psychosocial adversity and comorbidity with conduct, mood and anxiety disorders to be predictors of persistence.[15] Nevertheless, all forms of ADHD are known to persist into adulthood including ADHD with predominantly inattentive symptoms and ADHD associated with milder levels of impairment and comorbidity.

The prevalence of ADHD in adults estimated from epidemiological studies is in the range of 2–5%.[16–19] Persistent forms of ADHD are thought to have a higher familial loading than ADHD that does not persist, with increased rates of ADHD among the parents and siblings of those with persistent ADHD and high rates of ADHD among the offspring of parents with ADHD.[20] Twin and adoption studies indicate that the familiality of ADHD symptoms results from genetic factors rather than shared environmental risks, providing a further rationale for considering ADHD as a lifetime condition.[21] ADHD occurs in around 10–20% of people with common mental health problems according to epidemiological and clinical research.[22–27] Further studies show that this rate may be higher in some clinical populations such as those attending forensic, addiction and personality disorder clinics, highlighting the importance of screening within such high risk populations.[28]

There is growing recognition of the importance of diagnosing and treating the disorder in parents of children with ADHD[29] since around 20% of parents of children with ADHD will have ADHD themselves.[30] Furthermore, parents with ADHD may have difficulty in implementing parent training strategies for the treatment of behavioural problems in their offspring. Since the recognition of ADHD is relatively recent throughout much of Europe there are in addition many adults with ADHD who were never diagnosed or treated for ADHD when they were children.[31] Recent national guidelines now recommend that ADHD should be recognised and appropriately treated throughout the lifespan.[32–34] Despite this, across much of Europe many professionals working in adult mental health services remain unaware that ADHD frequently persists into adult life and remain uninformed about the clinical presentation and the consequences of ADHD across the lifespan.

Another reason for underdiagnosis and treatment of ADHD in adults is the age-dependent change in the presentation of ADHD symptoms. The more overtly impairing symptoms in childhood, hyperactivity and impulsivity, often become less obvious in adulthood, shifting the problem to more subtle symptoms such as inner restlessness, inattention, disorganisation and to impairment in behaviours related to executive functioning; and this may lead to discontinuation of treatment when they are still required.[13,31,35–39] Additional reasons for underdiagnosis of ADHD include the frequent presence of comorbid psychiatric syndromes, which in clinical practice may be identified as the primary or only diagnosis. Finally, stigma and myths continue to surround the condition and its treatment, particularly with stimulant medication.[40,41]

Stigma in General and among Professionals

ADHD is an established disorder in childhood with child and adolescent mental health or paediatric services for ADHD available across most of Europe. Yet adult services for people with ADHD remain relatively scarce despite strong evidence for the benefits of diagnosing and treating ADHD in adults (reviewed in [32]). There are still many professionals that are unsure of the diagnosis and the appropriate use of ADHD medications in adult mental health. Some continue to express fears about treating a 'non-existent disease' or causing drug addiction with stimulant medication, despite evidence to the contrary.[42] The reasons for this are likely to be based on the historical perception of ADHD as a disorder that is restricted to childhood and the continued presence of stigma and clinical mythology that surrounds the disorder and its treatment; and the traditional separation of adult from child psychiatry. What is clear is that there remains a gulf in the perception of the disorder between those working in paediatric and child and adolescent mental health services and those working in adult mental health, that cannot be explained on the basis of validated evidence based information.[43]

Stigma related to the term ADHD is one component of the problem that nearly always arises in the context of lack of awareness or understanding of available data. Within the mental health profession stigma is further associated with the restricted regulatory status in many countries for most of the medications that treat ADHD in adults, but has other reasons as well. ADHD in adults remains a disorder which is poorly understood and where an 'emotional burden' is attached to the term especially among professionals who have not traditionally been involved in the diagnosis or treatment of ADHD.[42,44,45] People suffering from ADHD are often stereotyped as lazy, bad or aggressive, or considered to have a behavioural or special needs problem rather than a mental health disorder that requires treatment.[44] The diagnosis may also be overlooked because ADHD is a highly symptomatic disorder and those less familiar with the onset, course, psychopathology and comorbidities associated with the disorder may mistake ADHD for other common mental health problems such as mood or personality disorders.

While increasing awareness and availability of accurate information is a high priority, many education programs for primary care physicians lack a component for ADHD so that a high percentage remain unaware of the way that ADHD affects people beyond the childhood years.[45] Furthermore, education about adult ADHD has not been included in most college programs for medical and psychology students, as well as training of professionals in adult mental health. Education programs therefore need to target all stages of professional development, from students through to primary and secondary care physicians and psychologists, to ensure appropriate early recognition, diagnosis and treatment are provided. Referral to specialist clinics should be possible where secondary care physicians lack sufficient training for more complex cases.

In terms of treatment, stimulants are by far the best studied and most effective treatment for ADHD across the lifespan, yet their use in some parts of Europe remains controversial in children and more widely across Europe in adults. The recent National Institute for Health and Clinical Excellence (NICE) guidelines from the UK describes the situation in which a drug treatment is considered safe to give to children but not safe to give to adults as an "anomaly".[32] The NICE guidelines have been pivotal in the UK by providing national guidance for the development of clinical services for adults with ADHD and the recommendation of stimulants as the usual first line treatment. As a consequence many new clinics are being established and increasing numbers of adults are provided with effective treatment in the form of stimulants, despite the lack of formal recognition by regulatory bodies for use of medicines. The current lack of licensed indications for the use of stimulants in adults in most European countries (but not in the US) is not supported by available data, but rather results from the historical focus on ADHD as a child disorder, commercial considerations by pharmaceutical companies and caution from regulators: a situation that may be revised in the next 1–2 years in Europe as several formulations of methylphenidate and dexamphetamine are being put forward for registration. However, a recent safety review of the use of methylphenidate from the European Medicines Agency, which restricts its recommendation to children over 6 years of age and adolescents and does not mention use in adults, has led to methylphenidate no longer being licensed for use in countries such as Norway.

Genes, Environment and Neurobiology

Family, twin and adoption studies show that ADHD is a familial disorder with high heritability, indicating that a significant genetic component influences risk for the disorder.[46–54] Environmental factors are also likely to play a role either as main causal factors in a few cases[55] or by interaction with genetic risks.

Family studies indicate a risk to first degree relatives of 4 to 10 fold the population rate, with prevalence among first degree relatives in the range of 20–50%.[20] Data from numerous twin studies of parent and teacher rated ADHD in children and adolescents indicate an average heritability (the variance explained by additive genetic factors) of around 76%,[56] indicating that familial influences on ADHD are largely genetic. Furthermore twin studies that have investigated the continuity of ADHD at various developmental stages indicate that continuity of symptoms across the lifespan is largely the result of shared genetic effects.[57–59] Yet, studies of self-rated ADHD symptoms in adult population twin samples consistently report lower estimates of heritability, in the region of 30–40% from two published[59,60] and one unpublished (Larsson et al., in preparation) study. The reasons for the lower heritability has not been fully investigated, but is likely to arise from the use of self-rating ADHD scales in population twin samples for two main reasons. First there may be a variable level of awareness among individuals when self-rating their own ADHD symptoms, leading to inaccurate ADHD symptom scores; and secondly self-ratings of ADHD symptoms may be confounded by adult onset conditions that generate ADHD-like symptoms, such as anxiety, depression, fatigue and drug and alcohol use. There is however as yet no empirical data to resolve these questions, so we have to conclude that further work is needed to fully understand the extent of genetic influences on ADHD in adults.

Molecular genetic studies in adults are relatively recent but are expected to confirm some genetic associations identified in childhood ADHD samples and find other genes that relate to persistence or remission of ADHD symptoms in adult life. There is a great deal of interest in the mechanisms by which the disorder persists in some individuals and remits in others, since this may identify new targets that prevent progression of the disorder into adult life. One potential mechanism is suggested by the developmental hypothesis of Jeffrey Halperin, which proposed that ADHD is linked to an early-appearing and enduring subcortical dysfunction (weak arousal mechanisms), while symptom remission is dependent on the extent of maturational changes in executive control.[61,62] The emphasis is on the interaction between these two processes, with remission or persistence of ADHD symptoms related to the emerging balance between cortical and sub-cortical function. Whether the processes involved can be neatly separated into sub-cortical versus cortical is uncertain and requires further detailed investigations, however a recent large international study obtained evidence that the same two processes account for 85% and 12% respectively, of the genetic influences on ADHD.[63]

Molecular genetic studies of ADHD in children provide direct support for the association of specific genes with ADHD. Genetic variants within or near to the D4 (DRD4) and D5 (DRD5) dopamine receptor genes provide the most consistent findings supported by meta-analysis.[64] Numerous other studies find evidence of association with the dopamine transporter gene (DAT1), the dopamine beta-hydroxylase gene (DBH), the serotonergic transporter (5-HTT), the serotonergic receptor (HTR1B), and the synaptosomal-associated protein, 25 kDa (SNAP-25).[48] Taken together these candidate gene findings are thought to explain around 3.2% of the variance in ADHD symptoms in children.[65] More recently whole genome association studies have identified novel genes such as CDH13 (a Cadherin gene) as potential risk factors[66] and rare copy number variants that confer higher risks in the order of odds ratios of 2–5, depending on general cognitive ability (Williams et al., reported at the World Congress of Psychiatric Genetics, 2009).

Molecular genetic studies have also turned to the study of ADHD in adults in recent years. Much of the current research coordinated in Europe by Barbara Franke from the Netherlands for the International Multicentre Persistent ADHD Collaboration (IMPACT) group. This collaboration has successfully generated a multi-site sample of around 3,000 patients and is continuing to develop. To date several publications highlight potential associations with ADHD in adults, some but not all of which are shared with genetic association findings in children.[67–72]

Environmental factors are also associated with ADHD,[73] particularly prenatal risk factors such as exposure to alcohol, nicotine, drugs, high blood pressure and maternal stress during pregnancy, as well as preterm birth and low birth weight.[74–76] Evidence from Romanian adoptees also suggests that severe early deprivation is causally related to ADHD.[55] In some cases the environmental measure may be mediated by genetic effects and may not always implicate environmental exposure as the primary causal factor. For example there is new evidence that prenatal exposure to nicotine may reflect genetic effects rather than the direct toxic effects of nicotine or other constituents of tobacco smoke.[77] Overall it is likely that environmental risk factors play an important role in the aetiology of ADHD and that in many cases the impact of the environment will be modified by genetic factors.

Neurocognitive, neurophysiological and neuroimaging studies suggest that brain dysfunctions are involved in the central components of the syndrome in children and adults.[78–82] Fronto-striatal dysfunction and increased dopamine transporter density in the striatum have both been reported[83–86] although the finding of increased dopamine transporter density remains a controversial finding, perhaps secondary to drug treatments for ADHD.[87,88] Magnetic resonance imaging (MRI) studies indicate smaller volumes of caudate, corpus callosum, cerebellum and right frontal areas, as well as increased cortical thinning.[89–97] Functional MRI data show differences in brain functioning between ADHD and controls including some studies of drug naïve patients.[91,98–103] Positron emission tomography (PET) shows abnormal cerebral glucose metabolism in prefrontal and premotor areas of the frontal lobe in ADHD adults.[104–106] In addition single photon emission computed tomography studies show studies show hypoperfusion and hypofunctioning of prefrontal and striatal regions in children and older adults with ADHD compared to controls.[107,108] The immediate and marked response of ADHD symptoms to stimulant medications such as amphetamines and methylphenidate, which increase levels of synaptic dopamine, suggests that the main underlying pathophysiological process may involve deficits or imbalances in catecholaminergic, dopaminergic, and nicotinergic functioning.[109–111]

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