Dr. Weisler is adjunct professor of psychiatry at the University of North Carolina Chapel Hill School of Medicine in Chapel Hill and adjunct associate professor of psychiatry and behavioral sciences at Duke University Medical Center in Durham, North Carolina. Dr. Goodman is director of the Adult Attention Deficit Disorder Center of Maryland at Johns Hopkins at Green Spring Station, assistant professor in the Department of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine, and director of Suburban Psychiatric Associates, LLC.
Disclosure: Dr. Weisler is/has been a consultant to Abbott, the Agency for Toxic Solvent Disease Registry/Centers for Disease Control, AstraZeneca, Biovail, Bristol-Myers Squibb, Corcept, Eli Lilly, GlaxoSmithKline, Johnson & Johnson, Novartis, Organon, Otsuka America Pharma, Pfizer, Sanofi-Synthelabo, Shire, Solvay, Validus, and Wyeth; is/has been on the speaker’s bureaus of Abbott, AstraZeneca, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Organon, Pfizer, sanofi-aventis, Shire, Solvay, Validus, and Wyeth; receives/has received grant support from Abbott, Biovail, Bristol-Myers Squibb, Burroughs Wellcome, Cephalon, Ciba-Geigy, CoMentis, Duke University Medical Center/National Institute of Health, Eisai, Eli Lilly, Forest, GlaxoSmithKline, Janssen, Johnson & Johnson, Lundbeck, McNeil, MediciNova, Merck, the National Institute of Mental Health, Neurochem, New River, Novartis, Organon, Parke Davis, Pharmacia, Pfizer, Pfizer Research, Saegis, Sandoz, Sanofi-Synthelabo, Schwabe/Ingenix, Sepracor, Shire, SmithKline Beecham, Solvay, Synaptic Pharmaceutical Inc., Takeda, TAP Pharmaceutical, UCB Pharma, Inc., Upjohn, Vela, and Wyeth; and has held or holds stock in Bristol-Myers Squibb, Cortex, Merck, and Pfizer. Dr. Goodman is/has been a consultant to GlaxoSmithKline, Eli Lilly, Forest, McNeil, New River Pharmaceuticals, Novartis, and Shire; is/has been on the speaker’s bureaus of GlaxoSmithKline, Forest, McNeil, Novartis, Shire, and Wyeth; receives/has received grant support from Cephalon, Eli Lilly, Forest, McNeil, New River Pharmaceuticals, and Shire; and receives/has received honoraria from Eli Lilly, Forest, McNeil, Novartis, Shire, and Wyeth.
Acknowledgments: Funding was provided by Shire Development Inc., Wayne, PA. Editorial assistance was provided by Robert Gregory, Timothy Coffey, and Rosa Real, MD, at Excerpta Medica in Bridgewater, NJ.
Please direct all correspondence to: Richard Weisler and Associates, 700 Spring Forest Rd, Suite 125, Raleigh, NC 27609; Tel: 919-872-5900; Fax: 919-878-0942; E-mail: RWeisler@aol.com.
• Adult attention-deficit/hyperactivity disorder (ADHD) has a profound effect on the lives of those with the disorder.
• There are numerous barriers to correctly diagnosing adult ADHD, including diagnostic criteria better suited to children, nonspecificity of symptoms, high incidence of comorbid disorders, and lack of definitive diagnostic instruments.
• Correctly diagnosing ADHD requires a multifaceted approach.
• Clinicians should maintain a high index of suspicion for ADHD in adults and include ADHD screening in all initial psychiatric evaluations.
• Stimulants are the first line of pharmacotherapy for ADHD in adults.
Attention-deficit/hyperactivity disorder (ADHD) is commonly perceived as a childhood disorder, but it persists into adulthood in 35% to 70% of affected people. The symptoms, deficits, and consequences associated with ADHD have a profound negative impact on the lives of patients and their families. Barriers to diagnosing ADHD in adults include diagnostic criteria developed and field-tested in children, nonspecificity of symptoms, high incidence of comorbid disorders that could mask or distract from the ADHD diagnosis, variation in presenting symptoms by gender and ethnicity, and lack of definitive diagnostic tools. Given the relatively high prevalence of ADHD compared with other psychiatric disorders, clinicians should maintain a high index of suspicion and integrate screening for ADHD into all routine psychiatric evaluations. Accurate diagnosis requires a comprehensive clinical interview, including evaluation of past and present symptoms and longitudinal course and assessment of functional impairment. It is often necessary to interview or obtain information from family, friends, coworkers, and old school or test records. A self-awareness of symptoms can be difficult for people who have lived most of their lives with the illness. Comorbid disorders may need to be treated before instituting treatment for ADHD. Education of patients and their families is an important facet of treatment that can improve adherence and optimize outcome. Pharmacologic therapy includes short- and long-acting stimulants as well as second-line nonstimulant medications. Short-acting stimulants may be inconvenient and have the potential for diversion and misuse. New treatments on the horizon may offer options better fitting the needs of adults with ADHD.
Until recently, attention-deficit/hyperactivity disorder (ADHD) was perceived as primarily a disease of childhood.1 Thus, diagnostic criteria and guidelines for the assessment, diagnosis, and treatment of ADHD in children are well established.2-5 ADHD usually becomes evident during childhood, but it persists into adolescence and adulthood in an estimated 35%–70% of cases.6-8 A nationally representative household survey of adults 18–44 years of age conducted in the United States in 2001–2003 reported an estimated 4.4% prevalence for ADHD.9 In surveys conducted by the World Health Organization (WHO) from 2001–2003, the prevalence of adult ADHD ranged from 1.2% in Spain to 7.3% in France (and 5.2% in the US).10
According to national surveys of ambulatory care visits to physicians’ offices and outpatient and emergency departments of general and short-stay hospitals, the proportion of adult patients diagnosed with ADHD making these visits increased from 2.1% in 1996–1997 to 3.7% in 2000–2001, and to 6% in 2002–2003.11 The number of prescriptions for ADHD medications has also shown substantial increases. Using pharmacy claims data for 2.5 million participants in prescription benefit plans, Castle and colleagues12 reported that during the period from 2000–2005, the annual growth rate in ADHD prescriptions for young adults 20–44 years of age was 17% for men and 21.4% for women. In contrast, the increase among children and adolescents ≤19 years of age was 9.5%. Recent data from Verispan13 indicates that prescriptions for ADHD medications for adults ≥18 years of age grew steadily from January 2003 through October 2007.
Nevertheless, adult ADHD remains largely underdiagnosed and untreated.8-10,14,15 In the US household survey,9 only 10.9% of adults with ADHD received any treatment for the disorder during the preceding year.
In spite of the need for diagnosis and management of adult ADHD, primary care physicians (PCPs), who are often an adult’s main healthcare provider, have little training in the assessment of adult ADHD.16 Moreover, numerous psychiatrists have had no training regarding ADHD in adults, despite reports from the 1970s and onward of the persistence of ADHD into adulthood.17 In a recent survey of 400 PCPs who regularly treat mental health disorders, 48% reported that they were not confident diagnosing adult ADHD, 44% considered the diagnostic criteria for adult ADHD to be unclear, and 72% reported it was more difficult to diagnose ADHD in adults than in children. Two-thirds deferred to a specialist when diagnosing adult ADHD compared with 2% when diagnosing depression and 3% when diagnosing generalized anxiety disorder.18
ADHD exerts a substantial toll on the lives of its sufferers and their families.1,19 This article explores the social and personal impact of ADHD on the lives of adults with this disorder, and the clinical challenges and opportunities for improving patient care through appropriate diagnosis and treatment.
The Impact of Untreated ADHD on Adult Lives
Functional and Psychological Impairment
ADHD has a wide-ranging impact on adult lives, manifesting as educational, interpersonal, physical, emotional, and work-related difficulties. Controlled studies1,20 demonstrate that adults with untreated ADHD have poorer educational performance and attainment, significantly more marriages, greater likelihood of problems making friends, and a higher incidence of interpersonal problems than those without ADHD. Adults with ADHD are also reported to have more symptoms of psychological distress, including hostility, depression, and anxiety, than non-ADHD controls.1 In the workplace, adults with ADHD are more likely to be fired from or quit a job impulsively, hold a single job for less time, have more job changes in a 10-year period, receive a lower salary, and have poorer work performance scores than their non-ADHD peers.1,19-21 In a 2003 national survey of 500 adults with ADHD (mean age=32 years) and 501 sex- and age-matched controls, significantly more psychosocial, educational, and occupational impairments were seen in those with ADHD. They had higher rates of divorce/separation and arrests and were less likely to be optimistic about their futures than non-ADHD controls; 72% felt that ADHD had a lifelong detrimental impact.20
Adults with ADHD may engage in risky or impulsive behaviors.22 They may demonstrate poor driving skills, have suspension or revocation of their driver’s license, receive more speeding tickets, and experience more motor vehicle accidents than those without ADHD.1,23,24 ADHD is recognized by the National Highway Traffic Administration as a contributing factor in motor vehicle accidents.25 Because accidents are the leading cause of death among people 16–30 years of age,26 the contribution of ADHD to these accidents adds to an already significant public health risk.
Tobacco use and drug and alcohol abuse are also more common in adults with ADHD than in the general population.9,27,28 A longitudinal study of the smoking status of 221 adults who had childhood ADHD reported a daily smoking rate of 35% compared with 16% of non-ADHD age-matched controls.27 In a study of 91 girls with ADHD 6–17 years of age, cigarette smoking was found to be a significant predictor of subsequent alcohol or drug use, abuse, and dependence.29 In the National Comorbidity Survey Replication (NCSR),9 those who satisfied criteria for ADHD were 3.0 times more likely to have a substance use disorder and 7.9 times more likely to be drug dependent than adults without ADHD; prevalence of substance use disorder was 15.2% for those with ADHD and 5.6% for those without ADHD (P<.05). Although the research is inconclusive, pharmacologic treatment for ADHD appears to reduce the risk of substance abuse.30-32
Adults with ADHD, especially those with comorbid conduct or oppositional defiant disorder histories, are more likely to engage in behaviors resulting in incarceration. In a study at the Utah State Prison of 102 randomized male inmates 16–64 years of age, 26 received a positive diagnosis of ADHD (having significant symptoms both as children and adults). An additional 22 inmates showed varying patterns of ADHD symptoms throughout childhood and adulthood, while seven had exhibited ADHD symptoms only during childhood, and seven showed ADHD symptoms only as adults.33 Of 129 inmates of a German prison for adolescent and young adult male prisoners, ADHD (using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition34 criteria) was diagnosed in 45%. Using International Classification of Diseases–Tenth Edition35 research criteria (“disturbance of activity and attention” or “hyperkinetic conduct disorder”), the prevalence was 21.7%.36 Conduct disorder and substance abuse are frequently seen with ADHD, but the risk of incarceration associated with ADHD appears to be independent of these comorbid conditions.37
The effects of ADHD may have a different impact on the lives of women than men. Women may receive the diagnosis later in life than men, perhaps because women tend to show more symptoms of inattention than of hyperactivity, the more conspicuous presentation.38 Women often blame themselves for their symptoms, damaging their self-esteem and resulting in depression.38,39 Traditional gender roles may also increase the impact of ADHD on women, as they are often employed in addition to being burdened with the multitasking role of family caretaker.38
Comorbidity and Economic Burden
Adults with ADHD are likely to have additional psychiatric and physical disorders.40 Comorbid conditions occurring frequently in adults with ADHD include substance/alcohol abuse, as well as mood, anxiety, learning, and personality disorders.9,10,41 The WHO epidemiologic surveys (n=11,422) reported that adults with ADHD were 4.0 times more likely to have an anxiety disorder, 3.9 times more likely to have a mood disorder, and 7.2 times more likely to have ≥3 psychiatric disorders than those without ADHD (P<.05).10 The NCSR (n=3,199) reported a prevalence of 38.3% for mood disorder and 47.1% for anxiety disorder among adults with ADHD.9 Among adults with bipolar disorder, those who also have ADHD are more likely to attempt suicide than those without ADHD.42 Rates of suicide in patients with bipolar disorder are estimated to be 15–22 times greater than in the general population,43 and ADHD can further compound the risks by increasing impulsivity, aggression, cigarette smoking, and substance abuse, which are independent risk factors for suicidality in patients with bipolar disorder.44-47 A history of suicide attempt was reported in 15% of 60 young adults with combined-type ADHD and in 3% of 36 young adults with inattentive-type ADHD.48 In an Austrian study,49 current suicidality was reported in 29% of incarcerated adolescent males diagnosed with ADHD.
Not surprisingly, ADHD poses a significant economic burden in terms of medical costs and work loss.21,41,50 Total excess healthcare and work-loss costs of childhood and adult ADHD in the US in 2000 were estimated to be $31.6 billion, of which $19.5 billion was directly attributed to excess healthcare costs for ADHD adults and their families, many of whom also incur additional healthcare expenses as a result of the ADHD of their impaired family member.50 Loss of workforce productivity due to ADHD among adults 18–64 years of age was estimated to be $67–$116 billion in 2003.21
Challenges in the Diagnosis of Adult ADHD
Shortcomings of DSM-IV-TR Criteria
There are numerous challenges to the correct diagnosis of ADHD in adults, particularly among those undiagnosed during childhood.51,52 Some of these challenges are related to the diagnostic criteria listed in the DSM-IV-TR.22 These require that patients have six of nine symptoms of either inattention or hyperactivity-impulsivity present for ≥6 months, have onset of symptoms before 7 years of age, impairment from the symptoms present in ≥2 settings (eg, work and home), and impaired social, academic, or occupational functioning (Table 1).22
The ADHD criteria of the DSM-IV-TR focuses on childhood expression of symptoms that may have limited applicability in adults; in fact, these criteria have never been validated in adults.14,15,53 Developmental, social, and environmental differences between children and adults affect the way in which symptoms manifest. For example, hyperactivity in children may be seen more as restlessness in adulthood; a child who squirmed, ran, or climbed might, as an adult, choose a physically demanding job or work excessively long hours.8,16,22 Thus, adult symptoms may be masked by compensatory choices in life situations or by development of coping skills that mitigate impairment. Further, symptoms may become apparent only in more challenging situations, such as at home with its demands for multitasking, and be less prominent in a work environment chosen for its suitability for ADHD.16,54 Adaptive skills, intelligence quotient, and environmental demands may make it difficult to enumerate the six of nine symptom criteria or to validate the two-domain criterion of the DSM-IV-TR. This adds to the need to revisit the conceptualization of ADHD subtypes in adults.
Because the DSM-IV-TR indicates that impairments from ADHD must have an onset during childhood, diagnosis involves establishing the presence of symptoms during childhood as well as assessing current impairment.22 The DSM-IV-TR requirement for manifestation of symptoms before 7 years of age relies on parental, peer, or self-memories of childhood occurrences or records for verification. Records, however, may be unclear, unavailable, or incomplete.22,51 Research indicates that retrospective diagnosis of childhood symptoms via self-rating by adults is a valid approach to meeting the DSM-IV-TR criterion of childhood onset.55,56 However, the necessity for symptoms before 7 years of age has come under question. A recent study identified a group of 79 adults who fulfilled all criteria for ADHD except for onset of symptoms before 7 years of age. Eighty-three percent recalled first symptoms between 7 and 12 years of age, and the other 17% had onset in adolescence or even adulthood.15 In a 20-year prospective follow up of adults diagnosed with ADHD by 6 years of age, their retrospective self-report age of onset was ≥4 years later than when it actually occurred.57 Thus, many adults with ADHD may not recall symptoms before 7 years of age, but most can recall symptoms by 12 years of age. The DSM-IV-TR would classify these patients as having a diagnosis of ADHD not otherwise specified (NOS) because they do not fulfill the age-at-onset criterion for ADHD.22 Gathering additional ADHD impairment data from family, friends, and school records from before 7 years of age can be helpful in many cases. It is important to remember that patients classified as having a diagnosis of ADHD NOS will also usually respond to approved treatments, as recently reported by Biederman and colleagues.58 In an open-label trial in 36 adults with late-onset ADHD NOS, an extended-release preparation of methylphenidate was associated with statistical and clinical improvement of ADHD symptoms.
Gender and Cultural Differences
Differences in ADHD presentation based on culture and gender pose another diagnostic challenge. As noted above, ADHD in adults occurs across ethnic groups and nationalities.9,10 However, the perceived importance of symptoms, or extent of impairment, may vary according to the cultural or family environment, and may affect what the patient and family consider problematic behaviors worth reporting to the clinician.8,59
Prevalence of ADHD is higher in boys than girls, with reported ratios of 2:1–9:1.22 Boys are more likely than girls to have the hyperactive subtype, learning disabilities, school behavior problems, and conduct or oppositional-defiant disorder.60 Among adults, the male to female ratio is reported to be approximately 3:2,9 and the expression of the disorder is similar in both sexes.61 However, because women may be less likely to have had ADHD diagnosed in childhood because of the absence or reduced intensity of hyperactive, disruptive behavior, they may require more effort to diagnose as adults. Moreover, numerous clinicians have a mistaken bias about ADHD being only a “male disease.”
Nonspecificity of Symptoms and Comorbidity
The diagnosis of ADHD requires the presence of six of nine symptoms of inattention or hyperactivity-impulsivity, but the individual symptoms in adults are nonspecific (ie, they are present in many healthy adults and may be seen in other psychiatric disorders such as major depressive disorder, mania, and generalized anxiety disorder).52 Shared and distinguishing features for ADHD and some common psychiatric illnesses are listed in Table 2.16,53 The presence of comorbid psychiatric disorders can mask or modify the presentation of ADHD symptoms, further complicating the diagnostic process.53,62 Adults may complain of symptoms of the comorbid disorder, which may be of new onset, while not mentioning symptoms of ADHD because these have been present since childhood and are not recognized as abnormal.16 Clinicians may then focus on the presenting diagnosed comorbid disorder and fail to identify or treat the underlying ADHD, potentially compromising treatment efficacy.
Inadequacy of Diagnostic Instruments
There is no accepted standardized diagnostic instrument for validation of adult ADHD compared with those available for other psychological disorders.9 Although current rating scales and neuropsychologic tests are cost-effective and helpful in assessing current symptoms in adults with suspected ADHD,8,51 results must be considered in light of the patient’s history. Interpretation of the self-report instruments requires proper training because adult psychopathology can distort perception on rating scales, and some self-report scales have poor specificity.52 Neuropsychologic testing, imaging, and laboratory tests can be helpful in understanding the cognitive and neural process underlying ADHD, but individual variability is such that they are not definitive for diagnosis and may add unnecessary costs.14,63,64
Making the Correct Diagnosis
Maintaining a high index of suspicion for the presence of ADHD in adults is a key aspect in making a correct diagnosis. Because of the high prevalence of adult ADHD relative to other major psychiatric disorders, screening for the disorder should be part of a comprehensive psychiatric evaluation.3 A useful screening tool is the WHO Adult ADHD Self-Report Scale Screener, a six-item subset (four inattentive and two hyperactive-impulsive) of the 18-question Adult Self-Report Scale (ASRS; Table 3).65 In a sample of 154 respondents who reported a diagnosis of childhood ADHD and persistence into adulthood, the six questions from Part A of the ASRS were found to be the most predictive of ADHD. This questionnaire has 65% sensitivity and 94% specificity for adult ADHD when a cut-off of 14 out of a total of 24 points is used.66
After screening, accurate diagnosis of ADHD requires a multifaceted approach including assessments of history, present symptoms, and functional impairment (Table 4).15,40,51,53 An accurate diagnosis requires sufficient presenting symptoms from the patient, with a pervasive course since childhood, and confirmation of childhood symptoms by an outside informant. Family history of ADHD further strengthens the diagnosis. The clinical interview should include a medical, educational, developmental, social, family, and psychological history. Interviewing family members greatly improves the clinician’s ability to correctly identify ADHD, as others often remember impairments that the patient has forgotten or failed to recognize. It can also be helpful to obtain school records to identify or corroborate childhood manifestations of ADHD.40 However, valuable supplementary information from family members or school records may often be somewhat difficult to obtain for adult patients no longer residing near their parents or schools.
Several standardized tools are useful in assessing adults with ADHD (Table 5).8,67 Diagnostic scales are either clinician administered (Conners Adult ADHD Diagnostic Interview, Brown ADD Scale Diagnostic Form, Brown ADD Scale) or self-reported (Barkley’s Current Symptoms Scales, which include evaluation by a family member). These tools vary with respect to whether they evaluate only current symptoms or include functional assessment and prior symptoms. Response to pharmacotherapy, psychotherapy, or both can be monitored by using the assessment scales through the course of treatment to evaluate target symptom changes.
Neuropsychologic deficits, including those of executive function, have been demonstrated in multiple studies of adults with ADHD, although results are heterogeneous across tests and patients.64,68,69 Executive dysfunction, evident in children with ADHD, has been shown to persist unchanged into young adulthood70 and has been reported to occur in adults with ADHD.71 Therefore, evaluation of adults with ADHD should include inquiries about deficits related to executive function such as difficulties in organization, working memory, time management, and ability to plan and think sequentially.64,72 Although neuropsychologic tests are not useful for diagnosis, evaluating these deficits may help clarify impairments of performance, guide treatment choices,64 and obtain work or academic accommodations.
Complete evaluation of an adult with suspected ADHD should also include assessment of comorbid psychiatric diagnoses and underlying medical conditions.52 Some medical conditions may have symptoms overlapping those of ADHD or can themselves account for certain attentional symptoms. These include impaired sight or hearing; medication side effects; and neurologic disorders such as sequelae of traumatic brain injury or cerebrovascular accidents, multiple sclerosis, or chemotherapy.73-76 Endocrine disorders such as thyroid diseases and diabetes, age-related conditions such as cognitive changes related to perimenopause, sleep disorders such as obstructive sleep apnea, and rare conditions such as Lyme disease should also be considered.77-83 Occasionally, treatable vitamin B12 or folate deficiencies are also found among adults with cognitive problems including ADHD84,85 when they are tested for serum levels of B12, methylmalonic acid (a more sensitive assay for B12 deficiencies), and folic acid. The critical factor in distinguishing many of these conditions from ADHD is the absence of childhood cognitive or behavioral symptoms consistent with ADHD.
Recommendations for Improving Care for Adult Patients With ADHD
Once the diagnosis is made, patient involvement is a key element in the success of managing ADHD in adults. Management can begin by educating patients and their families about ADHD.16,86 This includes discussion of the genetic contributions to ADHD, how ADHD is diagnosed, its presenting symptoms, and how comorbid conditions will be addressed in the treatment plan.16,87 The patient (and his or her family) can be taught to see ADHD as a treatable disorder rather than as an intrinsic part of their character, and they can begin to understand the impact that untreated ADHD has on their lives.16,86
After patient and family education, other treatment principles can help improve therapeutic outcomes. When significant psychiatric comorbidities such as affective, anxiety, or substance use disorders are present, it is best to treat them with appropriate therapies before targeting the symptoms of ADHD.87 In addition, once appropriate treatment options and objectives are identified, the clinician should explain the expected time course for symptom improvement, as well as potential adverse effects of prescribed medications, and emphasize that using prescribed medications on a consistent basis can improve and maintain the patient’s quality of life.16,40 The importance of involving family members in the overall management process should also be discussed, as should patient expectations and any reservations they have about treatment. Providing long-term support and encouragement at follow-up sessions is intrinsic to the treatment process and can also serve to significantly increase the often poor treatment adherence seen in ADHD.
Pharmacologic Treatment of Adult ADHD
Stimulants are the first line of treatment for ADHD.3 Stimulants, including methylphenidate and amphetamines, have been widely and successfully used in children for decades. Current pediatric guidelines recommend them as first-line therapy.2,3,5 Fewer controlled trials of stimulants have been conducted in adults than in children,88 but results of such studies in adults are similar to those in children and adolescents.89 Controlled trials in adults report significantly greater improvements with stimulants than with placebo, and response rates of 54% to 78% are seen using standard rating scales.89-94
Reported adverse events with stimulants are generally mild or moderate in severity and include reduced appetite, weight loss, anxiety, dry mouth, headache, and insomnia.89,94 Small increases in blood pressure and pulse have been reported in patients receiving stimulants. Cardiovascular status, especially blood pressure, should be monitored while the patient is receiving stimulants. Patients with poorly controlled hypertension may not be eligible for stimulant treatment until their blood pressure is well controlled.91,92 Before prescribing stimulants, clinicians should ensure that the patient has no structural cardiac abnormalities or other serious cardiac problems that may place him or her at increased vulnerability to the sympathomimetic effects of stimulant drugs.
Amphetamine and methylphenidate preparations are available in both immediate- and extended-release formulations. Immediate-release preparations require multiple daily dosing and are more likely to be diverted for misuse and abuse than extended-release formulations, a situation that is more common in adults and adolescents than in children.95,96 A recent study explored total retail prescriptions for long-acting and short-acting medications for ADHD by PCPs, pediatricians, and psychiatrists.96 Approximately 7 million patients in the US filled ≥1 prescription for their ADHD in 2007, with approximately 80% being written by PCPs (21%), pediatricians (28%), or psychiatrists (30%). The selection of short-acting or long-acting ADHD treatments varied by specialty, with long-acting agents representing 56% of primary care prescriptions, 64% of psychiatrist prescriptions, and 79% of pediatric prescriptions. When examined by patient age, long-acting agents accounted for 78% of ADHD prescriptions in pediatric patients (0–17 years of age), but only 49% of adult ADHD prescriptions. Extended-release preparations of methylphenidate, dexmethylphenidate, mixed amphetamine salts, and lisdexamfetamine are approved by the US Food and Drug Administration for use in adults without age restrictions.
Nonstimulants are used as second-line treatment of ADHD when the patient does not respond to first-line therapy, does not tolerate stimulants, or has an active substance use disorder.2,3,97 The nonstimulant atomoxetine is approved by the FDA for use in adults and has been shown to be effective in reducing symptoms of ADHD in adult placebo-controlled trials and in an open-label long-term study.98-101 A delayed time to onset (2 weeks) of a response to atomoxetine has been reported in adult patients.100 Atomoxetine is generally well tolerated and has no abuse potential; the most frequently reported adverse events in clinical trials were dry mouth, insomnia, and nausea.16 A few cases of serious liver injury have been reported in patients receiving atomoxetine, which should be used with caution in patients with cardiovascular or cerebrovascular disease because it can increase blood pressure and heart rate.102
In 2005, the possibility of suicidal ideation with atomoxetine led to an FDA boxed warning similar to that for antidepressant medications for children and adolescents, but no such warning was required in adults based on analysis of the adult studies. Nonetheless, it is prudent to be alert for suicidality in all patients with ADHD regardless of the choice of treatment and, in particular, in those patients with comorbid mood, anxiety, and substance use disorders. Double-blind studies in adults with ADHD have been positive for guanfacine, desipramine, and bupropion, but their use remains off label.103-107
The FDA has recently approved the use of two long-acting stimulants in adults with ADHD: a prolonged-release formulation of methylphenidate and lisdexamfetamine dimesylate, a long-acting prodrug.
In June 2008, the FDA approved the use in adults of a formulation of methylphenidate (MPH) in which the drug is released via an osmotic release oral system (OROS). The OROS-MPH formulation, which is designed to deliver MPH in a controlled manner for approximately 12 hours with a once-daily administration, has been shown to be efficacious and well tolerated in children and in several recent studies in adults with ADHD.108-110 In a double-blind study by Medori and colleagues,110 401 adults 18–63 years of age with ADHD received 18 mg, 36 mg, 72 mg, or placebo daily for 5 weeks. The primary measure of treatment response was the Conners Adult ADHD Rating Scale. At treatment end point, significantly greater improvements in rating scale scores were seen in patients receiving each of the three doses of OROS-MPH than in the placebo patients (effect sizes of .38, .43, and .62, respectively). Most adverse events were mild or moderate in each treatment group and few patients discontinued treatment because of an adverse event.
In April 2008, the FDA approved the use in adults of a new once-daily stimulant, lisdexamfetamine dimesylate (LDX), the first long-acting prodrug indicated for the treatment of ADHD in children and adults. LDX is a therapeutically inactive molecule, but after oral ingestion it is converted to l-lysine, a naturally occurring essential amino acid, and active d-amphetamine, responsible for the drug’s activity. LDX was developed with the goal of providing a long duration of effect that is consistent throughout the day. Clinical trials of LDX in children have demonstrated significant improvements in ADHD rating scale scores compared with placebo and consistent times to maximum plasma LDX levels among the subjects.111,112 Similar results have been seen in adults. In a double-blind, placebo-controlled, parallel-group study in 420 adults 18–55 years of age with a primary diagnosis of ADHD, improvements from baseline in ADHD Rating Scale and Clinical Global Impressions scores throughout the 4-week study period and at endpoint were significantly greater with three doses of LDX than with placebo (P<.0001 and P<.01, respectively).113 In addition, the prodrug formulation was developed to offer reduced potential for abuse-related liking effects. In a double-blind crossover study114 (n=36) of substance-abusing adults, the increase in the “liking score” after 100 mg of oral LDX on the Drug Rating Questionnaire-Subject did not differ significantly from placebo and was significantly less than the liking score increase after an equivalent dose of immediate-release d-amphetamine (P<.04). However, at 40 mg of d-amphetamine and 150 mg of LDX, between-group differences in changes in liking scores were not significant.
Current FDA-approved medications for the treatment of ADHD in adults are listed in Table 6, together with their generic and trade names and dosing information.102,115-118
Nonpharmacologic Treatment of Adult ADHD
In addition to pharmacotherapy, nonpharmacologic interventions, such as helping the patient restructure their environment, develop organizational skills, and create better coping strategies, may be beneficial in adults with ADHD.16 Because ADHD affects the entire family, treatment interventions may involve the spouse and children in restructuring of task sharing, planning, and day-to-day functioning. Cognitive-behavioral psychotherapy and structured problem-solving and coping-skills training for ADHD may also improve residual deficits and symptoms that may persist in spite of medication therapy.119-125
The Algorithm presents a schematic to select a specific psychotherapy for target symptoms and impairments.87 A thoughtful conceptualization and application of psychotherapy will prevent the therapist from being distracted. Because it is the very nature of the patient to be disorganized and distractible, organization and focus on the part of the therapist will ensure adherence to the therapeutic pursuit.
Adult ADHD remains under-recognized, underdiagnosed, and undertreated by clinicians in the US. Its prevalence and the absence of relevant professional clinical training indicate a need to educate physicians and other healthcare providers who encounter the challenging task of diagnosing ADHD in adults. Updated DSM-IV-TR diagnostic criteria that recognize adult-specific symptoms and reconsider age-threshold criteria for symptom onset are needed. Meanwhile, clinicians can improve patient care and provide a better quality of life for these patients and their families by maintaining a high index of suspicion for ADHD, making screening for the disorder an intrinsic part of the standard psychiatric evaluation, and implementing a multifaceted approach to the diagnosis and treatment of adult ADHD.
Stimulants that have been used in the pediatric ADHD population for decades are effective and well tolerated in adults. Management of ADHD in adulthood requires the clinician to rule out fairly common medical conditions, such as hypertension, that may be exacerbated by stimulant treatment. Significant cardiac disease in most cases precludes the use of stimulants in both adults and children. However, risk/benefit assessment and a cardiologic consultation may be necessary when the severity of ADHD leads to severe life impairments. Longer-acting forms of stimulants and nonstimulants can improve convenience and extend control of ADHD symptoms in challenging adult environments and potentially may help decrease, but by no means eliminate, the likelihood of stimulant abuse and diversion. In a recent analysis96 of US prescribing patterns, long-acting medications were still being used more commonly to treat ADHD in children and adolescents (78%) than in adults (49%), though adults may have even greater problems with treatment adherence and drug abuse and diversion than those ≤18 years of age. Alternative medications offer options to those patients with stimulant intolerance or special clinical circumstances such as active substance abuse.
The development of diagnostic tools and treatment guidelines, coupled with the use of effective and tolerable medications and effective management of comorbid conditions, should improve the quality of care for adult patients with ADHD. Improved recognition and treatment of ADHD should result in improved productivity in academic, work, and home environments, and should enhance quality of life for both patient and family. Future research may demonstrate whether intervention for ADHD can reduce morbidity and mortality from tragic outcomes associated with ADHD such as increased rates of motor vehicle accidents, suicide, and substance abuse and dependence. PP
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