In the mid-1970s, attention-deficit/hyperactivity disorder (ADHD) was still believed to be a childhood disorder that disappeared with the onset of adolescence. At this time, Wender studied a cohort of adults presenting with ADHD-like symptoms, all of whom had been diagnosed with ADHD in childhood. Wender prescribed psycho-stimulants, which successfully produced a response in the adults, thus fostering research into adult ADHD.

Objective: To evaluate the long-term safety and effectiveness of lisdexamfetamine dimesylate (LDX) in the treatment of adults with attention-deficit/hyperactivity disorder (ADHD).

Methods: Following a 4-week, placebo-controlled, double-blind trial, 349 adults with ADHD were enrolled into an open-label, single-arm study for up to 12 months. Treatment was initiated at 30 mg/day and titrated up to 70 mg/day at subsequent visits to achieve optimal effectiveness and tolerability. Safety assessments included adverse events inquiries, vital signs, and electrocardiograms while the primary effectiveness assessment was the ADHD Rating Scale (ADHD-RS) total score.

Results: A total of 191 (54.7%) subjects completed the study. The most common treatment-emergent adverse events (TEAEs) were upper respiratory tract infection (21.8%), insomnia (19.5%), headache (17.2%), dry mouth (16.6%), decreased appetite (14.3%), and irritability (11.2%). Most TEAEs were mild to moderate in severity. At endpoint, small but statistically significant increases in pulse and blood pressure were noted. Significant improvements in mean ADHD-RS total scores were observed at week 1 and sustained throughout the study (P<.0001 at all postbaseline visits). At endpoint, the mean improvement from baseline ADHD-RS total score was 24.8 (P<.0001).

Conclusions: LDX demonstrated a safety profile consistent with long-acting stimulant use and provided continued effectiveness in adults with ADHD for up to 12 months.

Attention-deficit/hyperactivity disorder (ADHD) may be the most common chronic, undiagnosed psychiatric disorder in adults. ADHD is characterized by restlessness, overactivity, disorganization, impulsivity, and inattention; and as further characterized in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). For most cases, an adult ADHD diagnosis is preceded by symptoms in childhood, which is a time when the disorder is rarely inquired about and usually overlooked.

ADHD has been recognized in children for several decades, and the importance of detection and treatment is well established. Whereas it was initially believed that children outgrew the disease, researchers now know that approximately two thirds of children affected with ADHD symptoms carry the condition into adolescence and then into adulthood. Consequently, >4% of adults in the United States have ADHD. Nevertheless, the disorder is unrecognized and untreated in the vast majority of these people.

Attention-deficit/hyperactivity disorder (ADHD) is a lifelong condition that begins in childhood and continues with adult manifestations related to the core symptoms. Approximately 50% to 75% of children with ADHD continue to meet criteria for the disorder as adolescents and adults. Adults with the disorder increasingly present to primary care physicians, psychiatrists, and other practitioners for diagnosis and treatment. Understanding the diagnosis of ADHD in adults requires knowledge of age-dependent decline of symptoms over time. Retrospective recall of symptoms and impairment are valid methods of diagnosing the disorder. ADHD is also a brain disorder with a strong neurobiologic basis, complex etiology, and genetic component. Genetic and environmental vulnerabilities give rise to abnormalities in the brain and subsequent behavioral and cognitive deficits, which may produce the symptoms associated with ADHD. Magnetic resonance imaging studies of ADHD have provided evidence that abnormalities in the brain are caused by the disorder itself rather than treatment of the disorder. Psychiatric comorbidity is common among patients with ADHD and tends to complicate treatment. Acute and long-term use of long-acting stimulant formulations (methylphenidate and amphetamine compounds) have shown robust efficacy and tolerability consistent with the treatment response established in children with ADHD. Non-stimulant medications have demonstrated efficacy as well, and may be preferred in patients with tic and substance use disorders.

In this expert roundtable supplement, Timothy E. Wilens, MD, reviews the epidemiology and clinical presentation of adult ADHD. Next, Joseph Biederman, MD, provides an overview of recent advances in the neurobiology of ADHD. Thomas J. Spencer, MD, reviews stimulant treatment of adult ADHD, and Lenard A. Adler concludes with a discussion of non-stimulant trials in adult ADHD.

How common is attention-deficit/hyperactivity disorder (ADHD), and does the prevalence change from adolescence to adulthood?

A number of studies have reviewed the persistence of attention-deficit/hyperactivity disorder (ADHD) from childhood into adolescence and adulthood as well as how the disorder changes over the lifespan of the illness. Recently, a metaanalysis found that the worldwide prevalence of childhood ADHD is ∼8%, and approximately two thirds of children with ADHD continue to have the disorder as adults. The National Comorbidity Survey is possibly the most comprehensive, up-to-date study examining the prevalence of community-based prevalence of adult ADHD; 4.4% of patients in that study were found to have ADHD. The prevalence of ADHD among adolescent patients seems to lie somewhere between the prevalence rates for children and adults.

Treatment of attention-deficit/hyperactivity disorder (ADHD) may positively impact the neurobiology of adult patients with ADHD. Treatment may also minimize impairment from core symptoms and may alter the course of co-morbid disorders such as depression and substance use disorder. However, much of the information on stimulant use in adult ADHD comes from studies conducted in children, and it remains unclear whether there is a difference between children and adults when it comes to the side effects and tolerability of ADHD treatments. It is known that clinical presentation differs between adults and children, with adults demonstrating a higher percentage of mood disorders. Current treatments for adult ADHD include psychosocial therapies and pharmacologic therapies, the latter of which include the stimulants d-methylphenidate extended release (XR), OROS methylphenidate, lisdexamfetamine, and mixed amphetamine salts XR; and the nonstimulant atomoxetine, a selective norepinephrine reuptake inhibitor. There is need for additional study of treatment strategies for adult ADHD. Although all classes of ADHD medications are approved in adults, there are fewer approved formulations for adults than for children. Efficacy in adults is more subjective than in children, which may affect how efficacy rates for adult treatments are calculated. Adults also present a greater diversion risk than children. In addition, there are several new and emerging medication treatments worth considering.

This Expert Roundtable Supplement represents part 2 of a 3-part supplement series on adult ADHD led by Lenard A. Adler, MD. In this activity, Thomas J. Spencer, MD, discusses the neurobiology and genetics of adult ADHD; Mark A. Stein, PhD, discusses stimulant therapy; and Jeffrey H. Newcorn, MD, reviews nonstimulants and psychosocial treatments.

Background. Identify a group of adults with ‘undiagnosed’ attention deficit hyperactivity disorder (ADHD) and compare their personal and family medical histories, psychosocial profiles, functional impairment and quality of life with non-ADHD controls. Additionally, compare adults with undiagnosed and diagnosed ADHD to investigate possible reasons why the undiagnosed avoid clinical detection.

Method. ICD-9 codes for ADHD in administrative claims records and responses to a telephone-administered adult ADHD screener [the Adult ADHD Self-Report Scale (ASRS)] were used to classify approximately 21000 members of two large managed health-care plans as ‘undiagnosed’ (no coded diagnosis; ASRS positive) or ‘non-ADHD’ controls (no coded diagnosis; ASRS negative). Patients identified as ‘undiagnosed’ ADHD were compared with samples of non-ADHD controls and ‘diagnosed’ ADHD patients (ICD-9 coded ADHD diagnoses) on the basis of demographics, socio-economic status, past and present mental health conditions, and self-reported functional and psychosocial impairment and quality of life.

Results. A total of 752 ‘undiagnosed’ ADHD subjects, 199 ‘non-ADHD’ controls and 198 ‘diagnosed’ ADHD subjects completed a telephone interview. Overall, the ‘undiagnosed’ ADHD cohort demonstrated higher rates of co-morbid illness and greater functional impairment than ‘non-ADHD’ controls, including significantly higher rates of current depression, and problem drinking, lower educational attainment, and greater emotional and interpersonal difficulties. ‘Undiagnosed’ ADHD subjects reported a different racial composition and lower educational attainment than ‘diagnosed’ ADHD subjects.

Conclusion. Individuals with ‘undiagnosed’ ADHD manifest significantly greater functional and psychosocial impairment than those screening negative for the disorder, suggesting that ADHD poses a serious burden to adults even when clinically unrecognized.