Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood and can profoundly affect the academic achievement, well-being, and social interactions of children; the American Academy of Pediatrics first published clinical recommendations for the diagnosis and evaluation of ADHD in children in 2000; recommendations for treatment followed in 2001.

https://pediatrics.aappublications.org/content/pediatrics/early/2019/09/26/peds.2019-2528.full.pdf

ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

Attention deficit hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that persists into adulthood in the majority of cases. The evidence on persistence poses several difficulties for adult psychiatry considering the lack of expertise for diagnostic assessment, limited treatment options and patient facilities across Europe. The European Network Adult ADHD, founded in 2003, aims to increase awareness of this disorder and improve knowledge and patient care for adults with ADHD across Europe. This Consensus Statement is one of the actions taken by the European Network Adult ADHD in order to support the clinician with research evidence and clinical experience from 18 European countries in which ADHD in adults is recognised and treated. Besides information on the genetics and neurobiology of ADHD, three major questions are addressed in this statement: (1) What is the clinical picture of ADHD in adults? (2) How can ADHD in adults be properly diagnosed? (3) How should ADHD in adults be effectively treated? ADHD often presents as an impairing lifelong condition in adults, yet it is currently underdiagnosed and treated in many European countries, leading to ineffective treatment and higher costs of illness. Expertise in diagnostic assessment and treatment of ADHD in adults must increase in psychiatry. Instruments for screening and diagnosis of ADHD in adults are available and appropriate treatments exist, although more research is needed in this age group.

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European consensus statement on diagnosis and treatment of adult ADHD: The European Network Adult ADHD.

Attention-deficit-hyperactivity disorder (ADHD) is a common neuropsychiatric disorder that impairs social, academic, and occupational functioning in children, adolescents, and adults. In patients with ADHD, neurobiologic research has shown a lack of connectivity in key brain regions, inhibitory control deficits, delayed brain maturation, and noradrenergic and dopaminergic dysfunction in multiple brain regions. The prevalence of this disorder in the United States is 6–9% in youth (i.e., children and adolescents) and 3–5% in adults. Prevalence rates for youth are similar worldwide. Children with ADHD are at greater risk than children without ADHD for substance abuse and delinquency whether or not they receive drug therapy; however, early treatment with psychoeducation as well as drug therapy and/or behavioral intervention may decrease negative outcomes of ADHD, including the rate of conduct disorder and adult antisocial personality disorder. Drug therapy is effective for all age groups, even preschoolers, and for late-onset ADHD in adults. Stimulants, such as methylphenidate and amphetamine, are the most effective therapy and have a good safety profile; although recent concerns of sudden unexplained death, psychiatric adverse effects, and growth effects have prompted the introduction of other therapies. Atomoxetine, a nonstimulant, has no abuse potential, causes less insomnia than stimulants, and poses minimal risk of growth effects. Other drug options include clonidine and guanfacine, but both can cause bradycardia and sedation. Polyunsaturated fatty acids (fish oil), acetyl-l-carnitine, and iron supplements (for youth with low ferritin levels) show promise in improving ADHD symptoms. As long-term studies show that at least 50% of youth are nonadherent with their drug therapy as prescribed over a 1-year period, longacting formulations (administered once/day) may improve adherence. Comorbid conditions are common in patients with ADHD, but this patient population can be treated effectively with individualized treatment regimens of stimulants, atomoxetine, or bupropion, along with close monitoring.

Attention-deficit-hyperactivity disorder: an update.

Neuromodulation of thought: flexibilities and vulnerabilities in prefrontal cortical network synapses.

OBJECTIVES Medications used to treat attention-deficit/hyperactivity disorder (ADHD) in adults have been well researched, but comparisons among drugs are hindered by the absence of direct comparative trials. Our objectives were to (1) estimate the effect size of the medications used to treat adult ADHD, (2) determine if differences in the designs of studies confound comparisons of medication efficacy, (3) quantify the evidence for differences in effect sizes among medications, and (4) see if features of study design influence estimates of efficacy. DATA SOURCES The following search engines were used: PubMed, Ovid, ERIC, CINAHL, MEDLINE, PREMEDLINE, the Cochrane database, e-psyche, and Social Sciences Abstracts. Presentations from the American Psychiatric Association and American Academy of Child and Adolescent Psychiatry meetings were reviewed. STUDY SELECTION A literature search was conducted to identify double-blind, placebo-controlled studies of ADHD in adults published in English after 1979. Only trials that used DSM-III, -III-R, or -IV ADHD criteria and followed subjects for > or = 2 weeks were selected. DATA EXTRACTION Meta-analysis regression assessed the influence of medication type and study design features on medication effects. RESULTS Nineteen trials met criteria and were included in this meta-analysis. These trials studied 13 drugs using 18 different outcome measures of hyperactive, inattentive, or impulsive behavior. After trials were stratified on the class of drug studied (short-acting stimulant vs long-acting stimulant vs nonstimulant), significant differences in effect size were observed between stimulant and nonstimulant medications (P = .006 and P = .0001, respectively, for short- and long-acting stimulants vs nonstimulants), but the effect for short-acting stimulants was not significant after correcting for study design features. The effect sizes for each drug class were similar in magnitude to what we previously reported for medication treatment studies of children with ADHD. We found significant heterogeneity of effect sizes for short-acting stimulants (P < .001) but not for other medication groups. CONCLUSIONS Although both stimulant and nonstimulant medications are effective for treating ADHD in adults, stimulant medications show greater efficacy for the short durations of treatment characteristic of placebo-controlled studies. We found no significant differences between short- and long-acting stimulant medications. Study design features vary widely among studies and can confound indirect comparisons unless addressed statistically as we have done in this study.

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A Comparison of the Efficacy of Medications for Adult Attention-Deficit/Hyperactivity Disorder Using Meta-Analysis of Effect Sizes

OBJECTIVE. With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder. METHODS. In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release (2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent9s Global Assessment, Conners9 Parent Rating Scale–Revised: Short Form, and Conners9 Teacher Rating Scale–Revised: Short Form. RESULTS. A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg (n = 87), 3 mg (n = 86), or 4 mg (n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: −16.18 in the 2-mg group, −16.43 in the 3-mg group, and −18.87 in the 4-mg group, compared with −8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent9s Global Assessment, Conners9 Parent Rating Scale–Revised: Short Form, and Conners9 Teacher Rating Scale–Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful. CONCLUSIONS. Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo.

A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.

Introduction:Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at α2A-adrenoceptors in the prefrontal cortex. A recent double-blind, multicenter trial supports the efficacy and safety of guanfacine extended release (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to study the safety profile and effectiveness of GXR for up to 2 years.Methods:Subjects were 240 children 6–17 years of age with a diagnosis of ADHD who participated in the preceding randomized trial. GXR was initiated at 2 mg/day and titrated as needed in 1-mg increments to a maximum of 4 mg/day to achieve optimal clinical response.Results:The most common adverse events were somnolence (30.4%), headache (26.3%), fatigue (14.2%), and sedation (13.3%). Somnolence, sedation, and fatigue were usually transient. Cardiovascular-related adverse events were uncommon, although small reductions in mean blood pressure and pulse rate were evident at monthly visits. ADHD Rating Scale, Version IV, total and subscale scores improved significantly from baseline to endpoint for all dose groups (P<.001 for all comparisons, intent-to-treat population).Conclusion:Long-term treatment with GXR was generally safe for up to 24 months of treatment, and effectiveness was maintained over this treatment period.

Raun D. Melmed

Papers

A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder.

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD.