Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder afflicting children and adolescents in the United States. Epidemiologic studies in the United States indicate that approximately 5% of youths have ADHD.1 ADHD is characterized by the childhood onset of symptoms of inattention, distractibility, impulsivity, and motor hyperactivity that occur in more than one domain of functioning (eg, home, work, school, socially).
Attention-deficit/hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder afflicting children and adolescents in the United States. Epidemiologic studies in the United States indicate that approximately 5% of youths have ADHD. ADHD is characterized by the childhood onset of symptoms of inattention, distractibility, impulsivity, and motor hyperactivity that occur in more than one domain of functioning (eg, home, work, school, socially). Symptoms must be debilitating and impair life functioning. Current diagnostic criteria for ADHD describe three subtypes: hyperactiveimpulsive, inattentive, and combined. The combined subtype is the most common. Boys predominate in an approximately 3:1 ratio, but evidence suggests that girls with ADHD, who may be more likely to have the inattentive subtype, are underdiagnosed and under-treated, though equally impaired, in comparison to boys.
ADHD is also quite common and impairing in adults. Indeed, studies indicate that 60% or more of children with ADHD will continue to exhibit debilitating symptoms, if not full syndrome criteria for ADHD, into adulthood. The high persistence rates of ADHD into adulthood and the associated impairments (debilitating effects on educational attainment, employment stability, social and marital relationships, driving, life satisfaction, and overall life functioning) are receiving increased clinical and research attention. The recently published National Comorbidity Survey Replication study reported that approximately 4.4% of U.S. adults (ie, 7 million) suffer from debilitating symptoms of ADHD. Adult rates indicate a 1.6:1 ratio favoring males over females.
Beyond Core Symptoms
Clinical studies of adult ADHD indicate that the disorder is more heterogeneous, and the symptoms subtler, in adults vs. children, which may partially explain why the disorder is largely underrecognized in adults. So too, the impact of ADHD and the consequences of the core symptoms of inattention, hyperactivity, and impulsivity, may be even greater, if expressed somewhat differently, in adulthood than in childhood. Adults with ADHD have elevated rates of disability in basic life functioning and are more likely to be unemployed or divorced. In one study of adult ADHD, 53.1% of women and 36.5% of men in the study cohort had received treatment for a mental or substance use disorder in the previous year, yet only 25.2% of the treated respondents had received treatment for ADHD, meaning that only 10.9% of the entire cohort with ADHD had received treatment for their ADHD symptoms in the previous 12 months. This treatment rate is strikingly low in comparison to rates for other psychiatric disorders, such as anxiety, mood, or substance use disorders, and further reflects the significant problems of underrecognition and undertreatment of adult ADHD.
Externally obvious symptoms of motor hyperactivity may become reduced from childhood to adulthood and give way to more inattentive symptoms. It is important to consider the associated symptoms of ADHD when evaluating a patient for ADHD. These symptoms of emotional over-reactivity, temper outbursts, and affective lability may affect up to one-third of adults with ADHD, causing them both significant functional impairment and adversely affecting their quality of life. Physicians screening for and evaluating adult ADHD need to be mindful about the high impact that the social and emotional symptoms associated with the disorder have in their patients’ lives.
Widening the perspective beyond core symptoms and asking questions that specifically elicit possible social and emotional functional impairments is key to a thorough evaluation of adult ADHD. Employment problems; feeling overwhelmed with life responsibilities; relationship problems with colleagues, spouse, or children; feeling disorganized; forgetfulness; and having a low tolerance for frustration and temper outbursts may all be a trigger to assess for undiagnosed ADHD. Until recently, ADHD has not been on the radar screen for many adult practitioners, and the likelihood is that many adult patients have suffered needlessly from untreated ADHD. It is important for clinicians to maintain a high index of suspicion for ADHD in the differential diagnosis of adults presenting with problems related to mood or anxiety, as nearly half of adults with ADHD have associated anxiety, and more than one-third have mood disorders. It is important to ask questions that can uncover ADHD-associated social and emotional impairments. This can result in more effective approaches to treatment and substantial reduction in the negative impact on patients’ lives.
Complicating ADHD’s clinical picture is the fact that as many as 50% of individuals with the disorder will meet the criteria for at least one comorbid psychiatric condition. In children, these coexisting conditions include learning disabilities, anxiety disorders, mood disorders, autism spectrum disorders, and other disruptive behavioral disorders, such as oppositional defiant disorder and conduct disorder. These disorders have an obvious impact on children’s abilities to function adequately in their academic, social, and family environments and, in combination with ADHD symptoms, often lead to adverse life outcomes and increased utilization of mental health, academic, and criminal justice system resources. In adolescents and adults, mood and anxiety disorders, as well as substance abuse disorders, commonly coexist with ADHD. Mood disorders, anxiety, substance use, and intermittent explosive disorder have been found to be 1.5 to 8 times more likely in adults with ADHD than in those without, and associated problems of frequent job changes, unemployment, and criminal arrests were found to be more common in this population as well.
Studies of driving behavior also indicate that adults with ADHD incur higher rates of accidents on the highway and motor vehicle—associated injuries.12 The fact that ADHD is likely to occur with other psychiatric disorders adds to the clinical complexity of both diagnosing and treating the disorder and amplifies the potential for adverse life outcomes. Comprehensive pharmacoeconomic data are lacking on ADHD’s impact in adulthood, but indirect indicators—such as the increased rates of criminal involvement, substance abuse, and psychiatric comorbidities, along with driving data—would suggest that ADHD is a costly disorder. Numerous studies have documented the high societal costs of depression, anxiety, and substance use disorders but have ignored the impact of comorbid ADHD. Given that ADHD is, by definition, a childhood-onset disorder, it would be useful to understand the impact of early diagnosis and treatment of the disorder on the development of subsequent comorbid conditions, as well as on the associated costs of treating these secondary conditions as they develop later in life. Whatever the age of clinical presentation, individuals with ADHD may have coexisting conditions that complicate diagnosis and treatment, add to the costs, and compound the impairments associated with the disorder.
It is not surprising that a disorder of primary attention and concentration marked by increased impulsivity, deficits in behavioral inhibition, and hyperactivity would cause impairments across many activities of daily life. In childhood, school failure, repeating a grade, disruptive behavior, disrupted family functioning, and difficulties forming and maintaining friendships characterize the impairments associated with ADHD. In adolescence and adulthood, the consequences of ADHD impairments may be magnified. Higher rates of teen pregnancy, sexually transmitted diseases (STDs), and substance use are among the more dramatic consequences of ADHD, but other impairments such as low self-esteem, poor relationships with peers and parents, and academic underachievement—despite adequate intelligence—are no less important. The pervasiveness of ADHD symptoms across adult life activities is striking. For example, adults with ADHD are more likely to receive speeding tickets, have their licenses suspended, and be involved in motor vehicle collisions. ADHD is associated with higher rates of divorce and separation, along with difficulty maintaining relationships with peers, affecting both work relationships and social interactions. Low tolerance for frustration, angry outbursts, road rage, social awkwardness, and impulsivity may characterize adults with ADHD.
These symptoms reflect the often overlooked social and emotional dimensions of impairment in adult ADHD. Impatience with spouses or children, disorganization, and lack of persistence at tasks may cause additional problems in the family setting. Research has demonstrated that substance abuse in adulthood has associations with ADHD and that failure to treat the disorder may result in a higher likelihood of substance use—associated problems. Studies have found that up to 71% of adult alcoholics had childhood-onset ADHD that was persistent, and 15 to 25% of adult alcoholics and drug addicts meet the criteria for ADHD. A large community study of adults with ADHD indicated significant personal and professional consequences of the disorder. These adults exhibited negative views of themselves and their outlooks for the future, had greater personal anxiety, lacked strong family and peer relationships, and were more likely to frequently switch jobs or be unemployed.
Assessment of ADHD entails a careful and comprehensive clinical evaluation, personal and family history, with close attention to the presence of complicating coexisting conditions. Treatment success often is limited by the failure to diagnose and treat such coexisting conditions. Despite advances in the technology of neurocognitive science, ADHD remains a clinical diagnosis, based on gathering a clinical history, assembling a timeline of symptoms, and identifying areas of impairment. There is no “test,” functional brain scan, or neuropsychological test that is definitive for ADHD. The diagnostic criteria for ADHD historically have been anchored in childhood manifestations of symptoms that may not adequately capture adult presentations of the disorder. Adults may demonstrate subtler and more complex expressions of ADHD’s core symptoms, which may evolve from childhood to adolescence into adulthood. For example, frank motor hyperactivity seen in childhood may give way to less overt expressions, such as an internal sense of impatience, or be seen in adults who start multiple projects without follow-through or completion. As awareness of symptoms may be low in both adults and children, it is important to use structured scales to effectively capture and quantify the intensity and range of ADHD symptoms. This often involves collateral sources of information, such as parents, teachers, or spouses.
It is important for clinicians evaluating adult ADHD to widen their diagnostic horizon and ask about social and emotional symptoms associated with ADHD, as well as core symptoms of the disorder. The impairments resulting from these social and emotional symptoms associated with ADHD may be the most meaningful and debilitating for adults with the disorder. Although not diagnostic for ADHD, many helpful paperand-pencil rating scales and checklist instruments can be used both for children and adults, such as the Conners ADHD Rating Scale21 and the Wender Utah Rating Scale for Adult ADHD. These instruments are useful in terms of specifying the target symptoms, in rating symptom severity, and in tracking treatment response. It is also important to assess baseline and subsequent changes in quality of life and life functioning measures. These are the “so what” of core symptom reduction and are the ultimate target outcomes for the treatment of ADHD.
Instruments such as the Adult ADHD Quality of Life (AAQoL) and the Life Participation Scale (LPS) are scales that capture important real-life functional changes for adults and children with ADHD, respectively. Finally, a thorough assessment of ADHD identifies the specific target symptoms and life impairments of the disorder, and also identifies comorbid diagnoses or symptoms of other psychiatric disorders—such as depression, anxiety, or substance abuse—that may be important targets for medical treatment intervention.
Optimizing treatment for ADHD involves tailoring treatment to the specific needs of individual patients, including consideration of coexisting conditions. Individuals with ADHD often exhibit highly complex symptom presentations, and there is no one-size-fits-all treatment approach suitable for patients with ADHD. The most powerful treatment intervention for core ADHD symptoms involves pharmacotherapy, although the use of adjunctive behavioral management, time management, and skills-based modalities may augment the utility of medication. Further, targeting coexisting conditions with additional medication or psychosocial treatment interventions is important to help improve the overall outcomes of individuals with ADHD. Many medications are available for the treatment of ADHD, and a significant evidence base of more than 250 randomized, controlled studies attest to their effectiveness in all age groups. Medication treatments of ADHD are among the most extensively studied, with well-characterized safety profiles. Further, clinical trials with ADHD medications have consistently shown robust effect sizes in the range of 0.6—1.0, which are among the highest in psychiatry. ADHD medications fall into two distinct categories: stimulants and nonstimulants. The medications share some characteristics, yet are sufficiently distinct in their mechanisms of action, formulations, or in their time-action effects to warrant consideration as discrete treatments for ADHD.
Stimulant medications include amphetamine and methylphenidate and their associated formulations. These agents are available in immediate-release (ie, short-acting), intermediate-acting, and long-acting formulations. Short-acting forms of methylphenidate require multiple daily dosing to achieve adequate symptom coverage throughout the day. Longer-acting versions of methylphenidate provide longer coverage with once-daily dosing in the morning. Agents differ in terms of the ratio of immediate- vs. delayed-release proportions of methylphenidate and exhibit relative differences in coverage of symptoms in the earlier versus later parts of the day.
A recently released transdermal patch of methylphenidate provides up to 12 hours of symptom coverage with once-daily application. Both the patch and the liquid formulation of methylphenidate can be useful in patients who have difficulty swallowing a capsule. Short and intermediate forms of amphetamine typically provide symptom coverage for three to six hours. One amphetamine agent is a mixed salt version of amphetamine that employs a beaded release formulation to provide longer symptom coverage with once-daily dosing.
A recently released stimulant formulation, lisdexamfetamine dimesylate, is a pro-drug using a combination of l-lysine covalently bound to d-amphetamine that is rapidly absorbed from the gastrointestinal tract and converted to d-amphetamine. Stimulants act on the brain’s dopamine and norepinephrine neurotransmitter systems. Although the precise pathophysiology of ADHD is incompletely understood, stimulants appear to act by enhancing the release of these neurotransmitters from storage vesicles in presynaptic neurons and interfere with subsequent reuptake (and thus inactivation of the neurotransmitter) back into the neuron after release.
Stimulants have the potential for abuse and have certain restrictions on their prescribing (eg, samples cannot be provided, refills cannot be phoned in to the pharmacy, and some states require triplicate copies of prescriptions). Side effects may include appetite suppression, insomnia, and a propensity to exacerbate tics and anxiety, and they should be used with caution in patients with known cardiac structural or rhythm disturbances. There are also warnings regarding their risk for cardiovascular and psychiatric side effects. All stimulants have a boxed warning in their labeling regarding the potential for abuse of these agents.
Strattera® (atomoxetine HCl) is the only nonstimulant medication currently available for the treatment of ADHD. It is approved by the US Food and Drug Administration (FDA) for use in children, adolescents, and adults with ADHD. Strattera is a selective norepinephrine reuptake inhibitor with little or no effect on other neurotransmitter systems. Animal studies have shown that Strattera, unlike stimulants, does not increase dopamine activity in the striatum or nucleus accumbens—an attribute that may be responsible for its lack of abuse potential and low propensity for causing motor or vocal tics.34 Strattera also may be the longest-acting agent available for the treatment of ADHD, based on evidence demonstrating that once-daily dosing provides symptom reduction measurable 24 hours after dosing. Strattera side effects may include appetite suppression, gastrointestinal upset, somnolence in children and adolescents, and insomnia in adults. Strattera can cause severe liver injury in rare cases. Strattera should be used with caution in patients with known cardiac structural or rhythm disturbances. Strattera has warnings for cardiac and psychiatric side effects. Strattera has a boxed warning for the rare (0.04%) occurrence of increased suicidal thoughts and behavior.
The art and science of treating ADHD require an understanding of individual patient needs beyond the basic core symptoms of the disorder, as well as identifying the presence of coexisting conditions that may require additional treatment considerations. Functional impairments related to ADHD need to be identified as targets for treatment. Outcomes and treatment goals should be developed based not only on core symptom reduction, but also on improvement in identified impairments and in overall quality of life associated with ADHD. The shift over the past decade from efficacy to effectiveness-oriented research expands the view of successful treatment as one in which overall functioning and perceived quality of living is improved. As always, a careful risk versus benefit assessment considering the safety and efficacy of treatment options should be the primary determinant in clinical decision making, and close follow-up should be maintained once treatment is initiated. Choice of medication is based on a variety of considerations, all designed to address individual ADHD patient needs. Patients who experience intra-dose “rebound” effects or who suffer debilitating symptoms in the late afternoon or evening may benefit from long-acting rather than immediate release formulations. Long-acting stimulant formulations provide rapid onset of action and coverage that extends over the course of the day without the need for multiple dosing.
In young patients or others who have difficulty swallowing a capsule, medications that need to be swallowed whole may not be the best first choice. Those that have a liquid formulation or that can be opened and sprinkled on food, as well as the transdermal formulation, may represent appropriate choices. The transdermal formulation also has the advantage of controlled offset of action, whereby parents or patients can remove the patch and expect offset of stimulant effect over roughly the following 1.5 hours.
For ADHD patients with a coexisting substance abuse disorder, anxiety, or tic disorder, a non-stimulant treatment for ADHD may be an appropriate choice. The non-stimulant may be preferred for patients with a coexisting substance use disorder, as the abuse liability is exceedingly low. If anxiety or a motor tic disorder is comorbid with ADHD, the non-stimulant may be an appropriate ADHD treatment choice. Evidence suggests that this agent neither causes nor exacerbates these conditions and, unlike many stimulant medications, does not carry contraindications or warnings around these coexisting conditions in labeling.41-43 Likewise, individuals who require long-duration symptom coverage may benefit from a non-stimulant choice as well. The best possible outcome in treating this often complex disorder involves clinician understanding of the differences between the variety of agents and choosing a particular agent based on each individual patients unique needs.
ADHD is a common disorder in childhood and adolescence that has high persistence rates into adulthood. ADHD increasingly is being recognized in adults, although symptoms may evolve. Recognizing the social and emotional impairments associated with ADHD, especially in adults, and not simply focusing on core symptoms, may result in better screening and more accurate diagnoses for the disorder. ADHD typically occurs with coexisting psychiatric disorders that, together with ADHD’s core symptoms, can result in complex clinical presentations and significant impairments in life functioning. Treatment approaches in ADHD need to take into consideration the specific complexities and coexisting conditions accompanying the disorder in individual patients. No single treatment is right for everyone. Patients have unique needs, and the optimum treatment for an individual patient involves tailoring specific medication and psychosocial interventions to target particular ADHD symptoms without exacerbating coexisting conditions of the patient. Reduction of ADHD core symptoms in tandem with targeting and improving functional impairments associated with ADHD may help to improve quality of life associated with ADHD for patients and their families. The good news is that ADHD is a treatable disorder and that—by tailoring treatment interventions based on individual patient needs—we can optimize functioning and substantially improve outcomes in the lives of patients and their families.
Craig L. Donnelly, MD, is Director of Pediatric Psychopharmacology and Associate Professor of Psychiatry and Pediatrics at Dartmouth Medical School.