Elsevier

The Lancet

Volume 395, Issue 10222, 8–14 February 2020, Pages 450-462
The Lancet

Seminar
Attention-deficit hyperactivity disorder

https://doi.org/10.1016/S0140-6736(19)33004-1Get rights and content

Summary

Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.

Introduction

Attention-deficit hyperactivity disorder (ADHD), like other psychiatric syndromes, has been refined and developed over the past 50 years, from its first contemporary description in the Diagnostic and Statistical Manual of Mental Disorders (second edition; DSM-II) as a hyperkinetic reaction of childhood to its current inclusion in DSM-51 as a lifespan neurodevelopmental condition with specific criteria for children and adults, a change reflected in its counterpart, the International Classification of Diseases (11th revision; ICD-11).2 This process of diagnostic evolution has been the result of periodic review and reformulation shaped by both research and clinical drivers. From a research perspective, the ADHD diagnostic formulation can be considered a part of a larger working hypothesis about the nature and structure of the disorder.3 As such, this diagnostic formulation is tested against empirical evidence so that it represents an increasingly accurate approximation of nosological reality as reflected in established research findings. Because the primary purpose of diagnostic systems is to provide intuitive and implementable guides for clinical decision making, the threshold for diagnostic innovation is set high and the pace of diagnostic evolution has been incremental in nature.4 Furthermore, as diagnostic systems in psychiatry have adopted a descriptive or phenomenological approach, considerations of the underlying causes of ADHD have been excluded from this process of re-evaluation and refinement. However, this diagnostic framework might be set to change. Progress in the aetiology and pathophysiology of ADHD challenges our current ways of thinking about the condition, while raising the prospect of new and potentially more effective clinical approaches.

Developing a broader range of more effective clinical approaches for people with ADHD, through the use of scientific discoveries, represents an important goal for the field.

ADHD is a prevalent, impairing condition that is frequently comorbid with other psychiatric disorders and creates a substantial burden for the individual, their family, and the community.5 Medication-based treatment strategies have proven efficacious and cost-effective in the short term and a number of compounds are available, recommended, and widely used.6, 7 However, the long-term effectiveness of these treatments on key educational, vocational, and social outcomes remains uncertain.8, 9 Furthermore, such effects are compounded by low adherence, especially after extended use in adolescence.10 These limitations are probably the result of both biological and psychosocial processes (eg, the build up of medication tolerance, ADHD-related stigma, and social resistance to medication).8, 11 Clearly, there is a pressing need for better long-term treatments for ADHD. By changing the way the field thinks about the causes of ADHD, scientific progress might help stimulate the development of new strategies for increasing the effectiveness of current treatments or the evolution of new alternatives. This Seminar will explore the issue of long-term treatment in three sections. The first section provides an account of the consensus about the clinical condition of ADHD, its diagnosis, epidemiology, developmental course, and treatment. The second section presents an up-to-date overview of ADHD science, focusing on advancements in aetiology and pathophysiology. The final section briefly explores how some of the most important scientific discoveries are beginning to challenge conceptions of ADHD in specific ways and examines the prospect that they will encourage new clinical perspectives and approaches.

Section snippets

Diagnosis

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.12 The American Psychiatric Association's DSM-5 defines ADHD in children (younger than age 17 years) as the presence of six or more symptoms in either the inattentive or hyperactive and impulsive domains, or both (panel 1). Fewer symptoms (ie, at least five symptoms in either domain) are required to meet

Scientific progress in understanding the causes of ADHD

Having reviewed the clinical consensus about ADHD as represented in DSM-5 and ICD-11, we now provide an overview of scientific developments in our understanding of the pathogenesis, causes, and pathophysiology of ADHD. Through this overview, we want to convey the great strides made by researchers in understanding the disorder. These developments will create a platform for our exploration of the ways in which science is challenging our conceptions of ADHD and how these insights might stimulant

What are the prospects for clinical advances in response to scientific advances?

In this final section, we briefly discuss four means by which scientific findings are challenging the way ADHD is conceptualised and explore the prospect that these can improve the diagnosis and treatment of ADHD in the future.

Conclusions

ADHD is a common, highly heritable, and impairing condition. Efficacious treatments are available but limited in many ways. We believe that the enormous strides made over the past 10 years by scientists in understanding the nature and causes of ADHD challenge accepted models of ADHD and might have the potential to encourage new clinical improvement. However, this advancement will take both time and considerable investment to identify the specific processes and systems to target, develop new and

Search strategy and selection criteria

We searched PubMed for articles published between Jan 1, 1980, and March 1, 2019, with an emphasis on the previous 10 years. English and non-English language publications were considered in our search. We included primary and review articles resulting from these searches, along with relevant references cited within those articles. Given the broad scope, yet restricted space, of our review, we occasionally cite review papers in place of primary reports. We used the search terms: “ADHD”,

References (136)

  • S Schwartz et al.

    Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: results from a comprehensive meta-analysis and metaregression

    J Am Acad Child Adolesc Psychiatry

    (2014)
  • FR Sallee et al.

    Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: a placebo-controlled trial

    J Am Acad Child Adolesc Psychiatry

    (2009)
  • MJ Lee et al.

    Attention-deficit hyperactivity disorder, its treatment with medication and the probability of developing a depressive disorder: a nationwide population-based study in Taiwan

    J Affect Disord

    (2016)
  • Z Chang et al.

    Risks and benefits of attention-deficit/hyperactivity disorder medication on behavioral and neuropsychiatric outcomes: a qualitative review of pharmacoepidemiology studies using linked prescription databases

    Bio Psychiatry

    (2019)
  • PJ Whitehouse

    Paying attention to acetylcholine: the key to wisdom and quality of life?

    Progress Brain Res

    (2004)
  • S Cortese et al.

    Neurofeedback for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials

    J Am Acad Child Adolesc Psychiatry

    (2016)
  • S Cortese et al.

    Cognitive training for attention-deficit/hyperactivity disorder: meta-analysis of clinical and neuropsychological outcomes from randomized controlled trials

    J Am Acad Child Adolesc Psychiatry

    (2015)
  • T Klingberg et al.

    Computerized training of working memory in children with ADHD—a randomized, controlled trial

    J Am Acad Child Adolesc Psychiatry

    (2005)
  • SV Faraone et al.

    Molecular genetics of attention-deficit/hyperactivity disorder

    Biol Psychiatry

    (2005)
  • JT Nigg et al.

    Low blood lead levels associated with clinically diagnosed attention-deficit/hyperactivity disorder and mediated by weak cognitive control

    Biol Psychiatry

    (2008)
  • JT Nigg et al.

    Prenatal smoking exposure, low birth weight, and disruptive behavior disorders

    J Am Acad Child Adolesec Psychiatry

    (2007)
  • D McCann et al.

    Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial

    Lancet

    (2007)
  • C Lugo-Candelas et al.

    Shared genetic factors, fetal programming, and the transmission of depression

    Lancet Psychiatry

    (2018)
  • J Nigg et al.

    Measured gene-by-environment interaction in relation to attention-deficit/hyperactivity disorder

    J Am Acad Child Adolesc Psychiatry

    (2010)
  • J Posner et al.

    Dissociable attentional and affective circuits in medication-naïve children with attention-deficit/hyperactivity disorder

    Psychiatry Res

    (2013)
  • JT Nigg et al.

    Causal heterogeneity in attention-deficit/hyperactivity disorder: do we need neuropsychologically impaired subtypes?

    Biol Psychiatry

    (2005)
  • FX Castellanos et al.

    Characterizing cognition in ADHD: beyond executive dysfunction

    Trends Cogn Sci

    (2006)
  • Diagnostic and statistical manual of mental disorders

    (2013)
  • International statistical classification of diseases and related health problems

    (2018)
  • JW Smoller et al.

    Psychiatric genetics and the structure of psychopathology

    Mol Psychiatry

    (2019)
  • D Coghill et al.

    Annual research review: categories versus dimensions in the classification and conceptualisation of child and adolescent mental disorders: implications of recent empirical study

    J Child Psychol Psychiatry

    (2012)
  • RM Scheffler et al.

    The global market for ADHD medications

    J Health Affairs

    (2007)
  • LD Adler et al.

    Review of medication adherence in children and adults with ADHD

    Postgrad Med

    (2010)
  • R Bussing et al.

    Barriers to detection, help-seeking, and service use for children with ADHD symptoms

    J Behav Health Serv Res

    (2003)
  • R.A. Barkley

    Major life activity and health outcomes associated with attention-deficit/hyperactivity disorder

    J Clin Psychiatry

    (2002)
  • ICD-11 for mortality and morbidity statistics (ICD-11 MMS), 2018 version

  • BB Lahey et al.

    Instability of the DSM-IV subtypes of ADHD from preschool through elementary school

    Arch Gen Psychiatry

    (2005)
  • GM Reed et al.

    Innovations and changes in the ICD-11 classification of mental, behavioural and neurodevelopmental disorders

    World Psychiatry

    (2019)
  • TE Moffitt et al.

    Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a four-decade longitudinal cohort study

    Am J Psychiatry

    (2015)
  • MH Sibley et al.

    Late-onset ADHD reconsidered with comprehensive repeated assessments between ages 10 and 25

    Am J Psychiatry

    (2018)
  • AJ Krasner et al.

    ADHD symptoms in a non-referred low birthweight/preterm cohort: longitudinal profiles, outcomes, and associated features

    J Atten Disord

    (2018)
  • A Caye et al.

    A risk calculator to predict adult attention-deficit/hyperactivity disorder: generation and external validation in three birth cohorts and one clinical sample

    Epidemiol Psychiatr Sci

    (2019)
  • GV Polanczyk et al.

    Annual research review: a meta-analysis of the worldwide prevalence of mental disorders in children and adolescents

    J Child Psychol Psychiatry

    (2015)
  • G Polanczyk et al.

    The worldwide prevalence of ADHD: a systematic review and metaregression analysis

    Am J Psychiatry

    (2007)
  • GV Polanczyk et al.

    ADHD prevalence estimates across three decades: an updated systematic review and meta-regression analysis

    Int J Epidemiol

    (2014)
  • S Collishaw

    Annual research review: secular trends in child and adolescent mental health

    J Child Psychol Psychiatry

    (2015)
  • DJ Safer

    Is ADHD really increasing in youth?

    J Atten Disord

    (2015)
  • M Rydell et al.

    Has the attention deficit hyperactivity disorder phenotype become more common in children between 2004 and 2014? Trends over 10 years from a Swedish general population sample

    J Child Psychol Psychiatry

    (2018)
  • V Simon et al.

    Prevalence and correlates of adult attention-deficit hyperactivity disorder: meta-analysis

    Br J Psychiatry

    (2009)
  • SV Faraone et al.

    The age-dependent decline of attention deficit hyperactivity disorder: a meta-analysis of follow-up studies

    Psychol Med

    (2006)
  • Cited by (392)

    View all citing articles on Scopus
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