Welcome progress in the diagnosis and treatment of ADHD in adolescence

By Mark A. Stein, PhD, and Martin Baren, MD

The prognosis for teenagers with ADHD is better than ever, thanks to more effective therapies and greater understanding of how the disorder manifests itself in adolescence. Successful management hinges on an appropriate medication regimen combined with academic and behavioral interventions.

It is now generally recognized that attention deficit hyperactivity disorder (ADHD) often persists into adolescence. Childhood ADHD has a major impact on the child, family, and school; adolescent ADHD results in an even wider range of impairments. The consequences of untreated or minimally treated ADHD in adolescents places an increasing burden on schools, social service agencies, and the criminal justice system. The cumulative effect of poor social and academic functioning can result in disenfranchised youth with poor employment prospects who become involved in criminal activities, including drug-related activities, and are at risk of developing other psychiatric disorders.¹

This pessimistic view is now being mitigated by a variety of new treatment options and increased awareness of ADHD. If managed appropriately, core symptoms can be reduced or normalized, reducing the negative impact of the disorder on adolescents, their families, and society. Effective management begins with an adequate diagnostic evaluation. However, because many primary care physicians and even mental health professionals are unfamiliar with the presentation of ADHD in teenagers, the diagnosis is often missed. [Editor's note: For an overview of the characteristics of ADHD in teenagers, see "ADHD in adolescents: Will you know it when you see it?" in the April 2002 issue.] This review considers the unique challenges of managing ADHD in adolescents and examines the roles of educational, behavioral, and pharmacologic treatments in addressing this persistent and destructive disorder.

Meeting the challenge of diagnosis

Accurate diagnosis of ADHD depends on a detailed clinical history, which is used to assess whether the adolescent meets the criteria for ADHD outlined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). At present, the DSM-IV criteria for ADHD are the same for children and adolescents, although adolescents generally display fewer and less obvious symptoms than elementary school-age children. Various tests can help rule out psychiatric and medical mimics and comorbid conditions. However, no objective test—psychological, laboratory, or neuroimaging—exists that can accurately and specifically identify adolescents with ADHD.² (For further discussion of conditions that mimic ADHD and comorbidities, see Baren³ and Pearl and colleagues.⁴)

The American Academy of Pediatrics (AAP) has issued guidelines for diagnosing ADHD in children from 6 to 12 years of age, most of which also apply to adolescents.² The guidelines propose how to obtain the relevant information and what sources are most useful, as well as providing guidance on the issues that need to be considered. Parents, teachers, and adolescents themselves are the key sources of information, along with past school and medical records.

The history is usually best obtained from the parents and the adolescent separately. In some cases, it is helpful to talk to the parents in the presence of the teenager to observe interaction or clarify a disagreement. We often meet with the adolescent first to engage the teen at an adult level and demonstrate the importance of his or her participation. Confidentiality and limits of confidentiality must be discussed at the beginning of the interview, especially because controversial questions about risky sexual behavior, substance use and abuse (including smoking), and potential legal issues often come up.

Rating scales are a valuable tool for gathering information from various sources efficiently. Note, however, that information, especially from school, may be more difficult to obtain and less valid for adolescents than for younger children because teenagers often have a number of teachers, many of whom do not know them well. Also, the more obvious symptoms of ADHD (hyperactive/impulsive behaviors) tend to diminish with advancing age, and parents and teachers may be less likely to notice the more subtle symptoms of ADHD (inattention, restlessness) in adolescents.

In addition to a complete history, a thorough physical examination should be conducted, including a neurologic examination and assessment of sleep behaviors to rule out conditions that either mimic or accompany ADHD.⁴ Further laboratory tests may be indicated based on the history and physical examination. A psychological or evaluation screening—including an individual IQ and achievement test like the WISC-III or WIAT-II—is extremely helpful because many teens with ADHD have specific or general learning disorders, particularly in written language.⁵ Last, we emphasize that a "positive" response to stimulant medication is NOT diagnostic of ADHD and should never be used to confirm the diagnosis.

Fostering cooperation and trust

The first hurdle in the management of the adolescent with ADHD is gaining his or her cooperation and trust. Establishing rapport should begin during assessment. Treating the adolescent as an adult during the initial appointment helps foster rapport and sets the stage for the teenager's involvement in decisions regarding treatment.

Remember, however, that self-reporting of symptoms by teenagers is highly variable; many lack insight into their own difficulties and are unwilling or unable to report them accurately.⁶ Even when they acknowledge problems, adolescents often blame others, notably their parents, teachers, and peers. For this reason, involvement of a parent or other significant person in the teenager's life is essential during diagnosis and when monitoring the effectiveness of treatment.

You should attempt to establish an open and confidential discussion with the adolescent, making him or her feel comfortable and assuring him that there is no collusion between physician and parents. Adolescents are often desperate to fit in with their peers and may be concerned that receiving treatment for ADHD will label them as abnormal, stupid, or crazy. Medication administration issues can exacerbate resistance to treatment, especially when short-acting drugs are used.⁷ Long-acting medications are much more appropriate, especially for this age group.

Some adolescents may perceive the diagnosis of ADHD as an excuse for imposing societal control over them. They may worry, among other things, that drug treatment is the equivalent of enforced submission or that medication may affect their personality, creativity, aggressiveness, or athleticism. Moreover, taking medication may conflict with the adolescent's own image of himself or herself as autonomous and invulnerable.

Even when medication is started successfully, adolescents with ADHD can be notoriously nonadherent. They need assurance at the beginning of treatment that they will be involved in any decision relating to management, particularly medication. For the adolescent whose ADHD is newly diagnosed, exposure to other teens with ADHD who are managing their condition well may help boost self-esteem. "Success stories" available through support groups, office reading material, or recommended Web sites—such as the Web site of Children and Adults with Attention-Deficit Hyperactivity Disorder: www.chadd.org —may be helpful.

Once adolescents realize that they can have their questions answered and they have a say in management, they are more likely to cooperate. We often recommend negotiating a contract with teenage ADHD patients to conduct a time-limited medication trial or participate in other treatments, such as family therapy.⁸ Encouraging the adolescent to draw up a list of positives and negatives associated with each form of treatment or medication also can help. The list can be jointly discussed to decide specific treatments and ways to evaluate outcomes.⁸ Discussion of perceived disadvantages can be used to dispel any inherent fears or myths that may be responsible for resistance to treatment.

Management options: More insight is needed

Although ADHD is one of the most studied childhood psychiatric disorders, the available treatment literature is predominantly based on the 6- to 12-year-old age group; the practice standards of the AAP for ADHD, for example, refer specifically to 6- to 12-year-olds.⁹ An extensive review of pharmacotherapeutic intervention studies¹⁰ identified only seven studies of adolescents, compared with 140 studies of school-age children. Relatively few data exist regarding important ADHD subgroups, such as girls and those with the predominantly inattentive subtype, and few empirically validated studies of psychosocial interventions have been done, despite the social and family impairments often associated with ADHD in teenagers. As a result, a huge disparity exists between the small pool of empirical investigations and the need for effective long-term management of adolescents with ADHD.

In the absence of empirically developed, adolescent-specific treatment guidelines, management is based largely on practices well established in children and adapted for teenagers. In general, a combination of educational, behavioral, and drug treatments targeting the individual adolescent's symptoms and impairments (so-called tailored multimodal treatment) is recommended for most adolescents with ADHD. To maximize long-term adjustment, the treatment plan also should emphasize and address identification of cognitive and interpersonal strengths.

Implementing educational strategies

The diagnostic assessment should not only focus on the symptoms and psychopathology of ADHD but should also evaluate cognitive, academic, and adaptive functioning to identify targets for intervention and strengths or protective factors to emphasize in the treatment plan. Common difficulties in teenagers with ADHD include poor organizational skills, limited self-monitoring, problems with working memory, and deficient planning skills, which often contribute to poor work output, especially as demands for independent work increase.¹¹ Difficulties with these so-called executive functions lead to ongoing problems with preparing for and taking tests, meeting deadlines, and completing homework, especially long-term assignments. In addition, deficiencies in working memory, coordination, and language can cause problems with note taking, copying assignments from the board, study skills, and writing in general.

If not addressed, these educational impairments can result in a moody, uncooperative, demoralized student. Parents and teachers often misattribute deficits to moral weaknesses or laziness rather than ADHD. As a result, the risk of school failure is high.¹² Management of the adolescent with ADHD must pay attention to educational issues, including early identification of both learning disabilities and strengths and development of an individualized treatment plan.

Academic and environmental interventions that may reduce educational difficulties include modifications in the adolescent's curriculum to compensate for neurodevelopmental weaknesses. Appropriate modifications include providing written instructions, preferential seating close to the teacher, and increased time for examinations; reducing the amount of written work; rewarding performance rather than speed; and breaking down long-term assignments into shorter ones (Table 1).

TABLE 1
Academic strategies to help students with ADHD overcome neurodevelopmental deficiencies

Selective recommendations from this comprehensive list are made for the individual patient.

Provide written instructions to accompany oral instructions

Assign student preferential seating close to the teacher or front of class

Check to make sure assignments are understood, copied correctly, taken home, and submitted on time

Suggest student use a laptop computer for writing and note taking

Increase time allowed for examinations

Reduce the amount of written work or use work sheets to avoid frustration

Encourage active reading with note taking

Avoid punishment for spelling, grammar, and punctuation errors

Encourage student to dictate reports and use a word processor

Reward performance rather than speed

Encourage performance in areas of strength (art, music, drama, athletics)

Avoid classroom humiliation (papers should not be graded by other students, for example)

Distribute notes before lectures

Assign note takers for student if necessary

Provide supervised study periods

Break down long-term assignments into shorter segments

Secondary schools and colleges are required by law to provide such accommodations to adolescents with ADHD (Table 2). For a student to be eligible for this kind of help, however, it must be demonstrated that symptoms of ADHD prevent the student from benefiting from the school's educational program.^13,14

TABLE 2
How federal law addresses educational services for adolescents with ADHD

Individuals with Disabilities Education Act (IDEA) of 1990 (and amendments of 1997) Part B

• Requires public schools to provide a free and appropriate education for all children with a disability

• To be eligible, evaluation must show the child has one or more specific physical or mental impairments that require special education. Adolescents with ADHD who do not have a specific learning disability may be eligible under the following categories: "Other health impaired" (because ADHD leads to heightened alertness to environmental stimuli resulting in limited awareness of the educational environment, which adversely affects educational performance and requires special education) "Co-existing specific learning disability" "Serious emotional disturbance" if problems in relationships with teachers and peers markedly impair educational performance

• Requires schools to identify adolescents with ADHD and use an Individualized Education Program (IEP) process to evaluate educational needs and plan an IEP tailored to each student

Section 504 of the Rehabilitation Act of 1973 and Americans with Disabilities Act (ADA) of 1990

• Modification of the regular curriculum is essential because of (1) a diagnosed impairment (ADHD) in an otherwise qualified individual that (2) substantially limits a major life activity (global learning and academic performance), (3) leading to a major disability compared to students of the same age and grade

• Requires public schools to provide free and appropriate education using regular education with various accommodations* or special education if necessary

*See Table 1

Source: Robin AL¹⁹

Although some schools are very receptive to academic accommodations, parents and primary care physicians may find many roadblocks in the path to implementing educational interventions. Some school districts or individual schools may try to block or simply ignore requests for this type of help. To minimize the barriers, primary care physicians must be aware of special education laws and provide adequate documentation of the need for formal evaluation of the adolescent's learning difficulties, whether or not the student has ADHD. [Editor's note: For more on this topic see "Educating children with disabilities: How pediatricians can help" in the September 2002 issue.]

If specific, well-documented requests for evaluation and treatment are ignored or refused, it may be necessary to pursue other means, such as requesting an independent evaluation or developing or revising the student's individualized educational program (IEP). In some cases, additional advocacy services are required. It may be necessary to request a due process hearing with the school district and, occasionally, consult with an attorney who specializes in special education law. "Legal clinics" associated with law schools sometimes can provide low-cost services. Ideally, differences can be resolved before the situation becomes adversarial. Gordon and Keiser¹⁵ and Latham and Latham^16,17 provide further recommendations for parents and primary physicians.

Using behavioral treatments

Behavioral and other psychosocial treatments are an important part of the management of adolescents with ADHD, who typically manifest several comorbid psychiatric disorders. Psychosocial treatment may be more effective in reducing impairments associated with comorbid learning or psychiatric disorders, building up strengths to enhance self-esteem, improving communication, or increasing adherence to treatment than in reducing core ADHD symptoms.¹⁸

Developmental milestones for adolescents include achieving a greater degree of independence, defining long-term academic or career goals, and establishing an identity separate from parents. It is important not to undermine these natural maturation processes. An implicit goal of intervention is to encourage the adolescent to assume greater responsibility for his or her own behavior. It should be noted, however, that adolescents with ADHD vary widely in severity of symptoms and maturity levels, which dictate the degree of independence and responsibility they can be allowed. Any behavioral or psychosocial intervention must consider the accepted norms for this age group.

Behavior therapy in teenagers with ADHD is more like marital therapy than parent training. The emphasis is increasingly on communication, compromise, and problem solving rather than discipline and rewarding adherence. Closely monitoring performance and establishing specific contingencies for positive and negative behaviors are key considerations.¹⁹ A detailed discussion of the different forms of behavioral therapy, which often require the involvement of a mental health professional, is beyond the scope of this article. We will briefly mention some possible interventions, however, to give an idea of what is involved. For more details the reader is referred to the discussion offered by Robin.²⁰

Exploring "hot" issues and previous roadblocks and clarifying communication styles are often the initial focus of treatment. Specific interventions have been developed that teach techniques to resolve or reduce parent–adolescent conflicts and manage the problems of daily life at home (problem-solving training, communication training, and behavioral parent management techniques).²⁰ Regrettably, economic, training, and manpower issues often limit access to these therapies.

Ratey and co-workers²¹ have developed another approach, which involves teaching techniques to enhance attention and memory as well as problem-solving techniques to improve family relationships. For example, asking patients to repeat information can improve listening skills, and introducing a structured problem-solving log can aid negotiation and socialization skills. Coaching patients in time management, organization skills, and anger-control techniques also is recommended. Such approaches, which involve equipping parents and teachers with effective management skills, have intrinsic appeal, and psychoeducational treatment is a standard part of research protocols and clinical practice.

One of the few well-controlled treatment studies of adolescents with ADHD found that behavior management training and parent–adolescent problem solving produced statistically significant improvements, although the magnitude of the effect was modest.²² Structural family therapy, in which the therapist takes an active, manipulative role in the organization of the family, also had only a moderate effect.

Evaluating the evidence supporting behavior therapy and other psychosocial interventions in ADHD is complicated by the fact that most treatment studies are short-term and often lack adequate follow-up in the child's or adolescent's usual environment. The impact of psychosocial interventions varies greatly across studies,⁶ and cited data are often anecdotal. It is clear, however, that more potent psychosocial treatment strategies, and perhaps better means of measuring their effectiveness, need to be developed, especially for teenagers.

A further difficulty with providing appropriate behavioral therapy is the limited availability of the necessary therapeutic skills and controls across home, school, and health-care settings to ensure consistent and durable standards of delivery. For this reason, it is helpful for the pediatrician to develop strong referral relationships with psychiatrists, psychologists, social workers, and family counselors who are skilled at working with adolescents with comorbid disorders and are accessible to the primary care physician. Key skills for both the general pediatrician and the specialists include the ability to establish rapport with the adolescent, while monitoring progress in school and peer relationships. Do not underestimate the need for brief but frequent communication between the mental health therapist and primary care physician!

Pharmacotherapy

For most adolescents with ADHD, drug treatment is required to achieve and maintain a clinically significant reduction in core ADHD symptoms. Only a minority of adolescents with mild symptoms are able to cope successfully at school with academic interventions alone. Drug therapy should therefore be presented to both patients and parents as an essential tool with which to manage ADHD, not as a last resort.

Stimulant medications are well established as the preferred first-line therapy for ADHD in all age groups. Methylphenidate (MPH), the most widely prescribed stimulant, is available in a number of formulations that differ in their duration of action (Table 3). The immediate-release formulation has a duration of action of only three or four hours and requires dosing two or three (sometimes four) times a day. Intermediate-acting and more recent longer-acting formulations require less frequent or once-daily dosing. Amphetamine-based treatments are also available in short-, intermediate-, and longer-acting formulations.

TABLE 3
Stimulant medications available for treating ADHD

A nonstimulant medication, atomoxetine (Strattera), has recently been approved for use in children, adolescents, and adults with ADHD. It may be an appropriate second-line therapy for patients who fail to respond to stimulant therapy or who desire an alternative to stimulants. No well-controlled, prospective, long-term study has yet compared the safety and efficacy of atomoxetine with long-acting stimulant medications.

Stimulants. The efficacy of stimulant medications, which have been used to manage ADHD for more than 50 years, has been established in numerous short-term studies in children.^23–26 It has been further confirmed in the few long-term studies that have been performed, including the Multimodal Treatment Study of Children with ADHD (MTA study)^27,28 and studies by Gillberg and colleagues²⁹ and Schachar and colleagues.³⁰ In these studies, approximately 70% of patients showed a positive response to medication, with a striking improvement or normalization occurring about 50% of the time. The rate of positive response increases to 90% when at least two stimulants are tried.³¹

Limited data in adolescents suggest that they respond in a similar manner to children. A recent 6-week, double-blind, randomized, crossover study evaluated the effects of multiple doses of MPH on academic performance and classroom behavior of 45 (predominantly male) adolescents with ADHD.³² Between 78% and 91% of the participants displayed a beneficial effect. These response rates are noticeably higher than those of earlier adolescent stimulant studies, which involved fewer patients.^33–35

More recently, the efficacy of the long-acting MPH formulation Concerta (OROS MPH) has been evaluated in a US community setting in a multicenter, open-label, nonrandomized study involving children, adolescents, and adults with ADHD.³⁶ This study is one of the largest community-based studies of ADHD in all age groups.³⁶ A group of 264 adolescents between 13 and 17 years of age were assigned to take a single morning dose of Concerta and assessed at baseline and three, six, and nine months. Parents/caregivers rated treatment as "good or excellent" in 84% of subjects after three months of therapy; this figure increased to 97% after six months. Similar results were reported for investigator assessments of the effectiveness of treatment. Parental satisfaction with medication was high—87% of parents were satisfied/very satisfied/extremely satisfied with treatment after three months—and only 6.8% of patients withdrew from the study because of side effects. A recent multicenter, randomized, double-blind, placebo-controlled study of Concerta in 175 adolescents with ADHD (13 to 18 years of age) also has shown significant benefit in this age group.³⁷

Stimulant medications are generally well tolerated and have few contraindications. Most side effects are mild, short-lived, and responsive to dose or timing adjustments.³⁸ The most often reported side effects include insomnia, reduced appetite, abdominal pain, headache, and dizziness.³⁹ Amphetamine-based medications tend to cause somewhat greater problems with sleep and appetite, consistent with their longer excretion half-life.³⁸ Individual response and sensitivities to stimulants vary greatly. Both MPH and amphetamines increase blood pressure and heart rate but the effects are usually clinically unimportant. Nevertheless, regular monitoring is recommended.

Concerns that stimulants may inhibit growth, especially in early adolescence, have largely proved unfounded. An examination of growth patterns by Vincent and co-workers⁴⁰ following administration of MPH for more than six months to 31 hyperactive adolescents revealed no significant departures from expected height and weight gains. Similarly, prospective follow-up into adult life has revealed no significant impairment of height.⁴¹ A more recent intermediate analysis that compared growth data for 287 children who had completed 12 months of therapy with Concerta with data for the general pediatric population (adjusted for age and sex, using z-score transformations and body mass index) demonstrated only very small deficits in mean height and weight gain and adequate body mass at all time points in this sample of children.⁴²

Adolescents also may be concerned about the effects of ADHD medication on their ability to participate in sports and other physical skills. Research in this area is limited. A literature review⁴³ concludes that while most patients with ADHD notice improved athletic performance during treatment, it is likely that the effects vary from athlete to athlete and among those participating in different sports. Moreover, improvements in concentration and fine motor coordination may be counterbalanced by a perceived reduction in aggression. Central nervous system stimulants are banned from use in competition by the International Olympic Committee.

Nonstimulants. Various nonstimulant agents, including antidepressants and antihypertensive medications, have been used in adolescents—usually those who fail to respond to stimulants, display comorbid mood or tic disorders, or are actively abusing substances. The only nonstimulant therapy approved specifically for treating ADHD is the selective norepinephrine reuptake inhibitor atomoxetine.

The efficacy of atomoxetine in children and adolescents has been demonstrated in three short-term (six or nine weeks of treatment), placebo-controlled studies—two involving 291 children 7 to 13 years of age⁴⁴ and one involving 171 youngsters 6 to 16 years of age.⁴⁵ All three studies showed statistically significant improvements in symptoms for atomoxetine compared with placebo.

One further open-label study of atomoxetine and MPH in 228 children 7 to 15 years of age (184 children received atomoxetine, and 44 received MPH) reported comparable efficacy for the two drugs.⁴⁶ In this study, however, MPH was administered one to three times a day, according to the investigator's judgment, and may not have resulted in optimal management considering the typical demands adolescents face throughout and beyond the school day.⁴⁷ It is therefore unclear whether atomoxetine is as effective as optimal MPH dosing.

No data are available yet regarding the long-term efficacy (and safety) of atomoxetine. In all studies except that of Michelson and colleagues,⁴⁵ atomoxetine has been given twice daily (morning and late afternoon). Although Michelson's study, in which participants were given atomoxetine once a day in the morning, showed evidence of drug-specific effects into the evening, some adolescents are likely to require twice-daily dosing. The usual starting dosage is 0.5 mg/kg/day.

Atomoxetine is generally well tolerated. The most frequent treatment-related adverse events (incidence 10% or greater) reported in placebo-controlled studies of atomoxetine include abdominal pain (20% vs 16% for placebo); vomiting (11% vs 9%); decreased appetite (14% vs 6%); headache (27% vs 25%); and cough (11% vs 7%).⁴⁸ Like stimulants, atomoxetine can increase blood pressure and heart rate, and regular monitoring is recommended. No data are available regarding effects on athletic performance.

Initiating drug therapy

Pharmacotherapy with either stimulants or atomoxetine begins with upward titration of the dosage until the optimal dosage is achieved (maximal control of symptoms with minimal side effects). Stimulants are usually started at a low dosage and increased at weekly intervals,³⁸ whereas the initial dosage of atomoxetine is increased after a minimum of three days.⁴⁸ If optimum symptom control is not achieved within a week with a given dosage, the dosage is increased to the maximum permitted dosage for each drug, assuming tolerability is not compromised. If the maximum permitted or tolerated dosage of a particular drug does not achieve adequate symptom control, an alternative medication should be evaluated.

Effects of therapy on ADHD symptoms can be assessed weekly over the telephone by asking the adolescent and parents about the positive effects of treatment and any adverse effects. Parent and teacher rating scales, which can be mailed or faxed to the office at regular intervals, can quantify stimulant response and assist in evaluating titration. Teacher ratings are more difficult to obtain for adolescents than younger children because teens have several teachers who often do not know each student well. A recent study found that although both parent and teacher ratings were sensitive in detecting effects of Concerta in 47 ADHD patients between 5 and 15 years of age, parent ratings were more sensitive.⁴⁹

How often patients are seen during the titration period varies widely. Some physicians schedule weekly appointments, whereas others prefer to see patients at the end of the first month. The medication follow-up appointment should include a brief clinical interview to discuss the positive effects of medication and any side effects or concerns, determine the impact of treatment on symptoms and impairments, and evaluate any additional comorbid problems that need to be addressed. It is also advisable to measure height, weight and blood pressure. Parents, teachers, and the adolescent should be asked to complete relevant rating scales before the visit. The results, together with any other information from schools such as report cards or progress notes, should be reviewed. This information can be used to determine whether or not a dosage adjustment is required.

The optimal dosage depends on individual target behaviors for the patient, which should be defined before initiating treatment. As has been well established in studies of children with ADHD, the dose-response curve is generally linear. Although individual sensitivity to stimulants varies widely, most adolescents benefit from a higher dosage and longer duration of effects compared to younger children. Rapport and colleagues report no consistent relationship between weight and clinical response,⁵⁰ but certainly many adolescents require a dosage significantly higher than what is used in younger children. In any case, dosages tend to be adjusted upward over time, as was evident in the landmark MTA study.²⁷

It is important to identify the optimum dosage because undertreatment, a common error, deprives the patient of the benefit of medication and fosters a negative perception toward medication. The impact of undertreatment was demonstrated in the MTA study, in which children in the community comparison group received a much lower daily dosage than those in the medication management groups and had significantly poorer symptom control.²⁷

Most adolescents require that symptoms be controlled beyond the school day and into the late afternoon and evening, when they may be participating in after-school activities, doing homework, and, in the case of older teenagers, driving, spending time with friends, and going to parties. Patients receiving a short-acting stimulant therefore need to take medication three or four times a day. More frequent dosing does not necessarily lead to more side effects and may result in greater clinically significant improvement.⁴⁷ However, adolescents often are concerned about taking a dose at school or immediately after school when they may be involved in a club or sport. For this reason, long-acting stimulants, such as Concerta or Adderall XR, are preferred for most teenagers.⁵¹ In some cases, adolescents may need to supplement long-acting stimulants with a short-acting stimulant to provide adequate coverage.

Concerta is a long-acting MPH formulation that has been extensively studied in children and shown to be superior to placebo and comparable in efficacy to the gold standard of ADHD treatment, MPH tid.^52–54 Concerta employs an osmotically-controlled delivery system to provide symptom control for 12 hours.⁵¹ An open-label study of patients treated with Concerta for as long as 24 months has shown that the drug maintains its effectiveness over time and is well tolerated.^55,56 Concerta also has been investigated in adolescents in an open-label study in a community use setting³⁶ and found to be superior in a multicenter, randomized, double-blind, controlled study described previously.³⁷

Adderall XR, a long-acting mixed amphetamine salt, has been shown to be superior to placebo in two short-term (three- and six-week) randomized studies in 584 and 51 patients, respectively, and to have a duration of effect of up to 12 hours.^57,58 The long-term safety and efficacy of Adderall XR is being evaluated in an ongoing open-label study in 516 children.⁵⁷ The 12-month interim analysis demonstrated maintenance of symptom improvement throughout the period, but reported that approximately 10% of patients withdrew from the study because of adverse events such as sleeplessness and weight loss. Adderall XR has not yet been evaluated in adolescents.

Adderall XR has been shown to reduce the plasma amphetamine concentration when taken by healthy adult subjects after a high-fat breakfast, compared to after an overnight fast.⁵⁹ In ADHD patients, the relationship between the plasma amphetamine concentration and clinical response is unclear, however. Patients should be cautioned that meals may affect medication response.

Recommended treatment strategy

Although a range of drug treatment options are available, considerations of efficacy, duration of action, and abuse potential suggest a clear strategy for initiating drug therapy in adolescents with ADHD. The significant advantages of the long-acting stimulant formulations, compared with short-acting stimulants, in terms of avoiding the need for midday or early afternoon dosing at school or college and providing longer symptom control, are, we believe, clear. In the absence of a well-controlled, prospective, long-term study contrasting long-acting stimulants with atomoxetine, stimulant medications are the first line of treatment based on their 50-year track record of safety and efficacy.

For the 10% to 15% of patients who do not respond to either MPH or amphetamines, or who display severe or chronic stimulant side effects, atomoxetine or an alternative stimulant or nonstimulant treatment should be considered. Because the mechanism of action of atomoxetine differs from that of the stimulants, such patients may respond to atomoxetine. Atomoxetine also may be a valuable alternative when tics or active substance abuse is a concern.

For patients who fail to respond to both stimulant and nonstimulant medications, the diagnosis should be reconsidered and the possibility of comorbid conditions entertained. Poor adherence or inadequate provision of information about the patient's behavior also should be considered. If ADHD is still found to be present on reevaluation, other medications—notably bupropion or tricyclic antidepressants (TCAs) such as desipramine—may be useful. TCAs are effective when depression or anxiety occur with ADHD and have been well studied as an ADHD treatment. In addition to bothersome anticholinergic effects such as constipation and drowsiness, TCAs have a much lower safety margin than stimulants for side effects, which include cardiotoxicity and lethal effects of an overdose.⁶⁰

Monitoring and reevaluation

Once successful management of ADHD symptoms has been achieved, periodic monitoring is required to ensure that symptoms are reduced or "normalized" and adverse effects are not present. The importance of such monitoring and adjustment of therapy as necessary was suggested by the results of the MTA study, which documented a significantly inferior outcome for the community treatment group, for whom the frequency of monitoring was not prescribed in the study design and can be assumed to have been less frequent than for the medication management group.²⁷ In patients with stable symptoms and no comorbidity, office visits every three to six months are probably sufficient; patients with a comorbidity may require more frequent monitoring and additional interventions or referrals.⁹

When the behavior or academic performance of a treated adolescent begins to deteriorate, evaluation of the range and extent of treatments, including medication dosage adjustments and psychosocial treatments, should be considered, depending on the area of concern. Emergence of additional problems, such as comorbid psychiatric disorders and alcohol and drug use, also should be explored.

A brighter outlook

Devising an appropriate treatment plan for the adolescent with ADHD depends on identifying appropriate target behaviors for treatment and assessing the patient's impairments and strengths. The plan must be updated and reevaluated at regular intervals. Active involvement by the teenager in treatment decisions reduces conflict with the primary care physician and facilitates compliance with treatment.

Educational, behavioral, and pharmacotherapeutic approaches have demonstrated varying degrees of efficacy and are probably most effective when used in combination. It is generally accepted that pharmacotherapy is the key to achieving control of the core symptoms of ADHD, however.

Although therapy is generally assessed in terms of its effectiveness in controlling the core symptoms of ADHD, the ultimate goal is to improve social and academic functioning. The prognosis for the adolescent with ADHD today appears much brighter than that suggested by the results of previous outcome studies, which typically looked at teenagers taking a short-acting stimulant for only part of the day—methylphenidate bid, for example. Increased recognition of the heterogeneous presentation of adolescent ADHD, along with innovative, effective, and palatable therapies, can mitigate the harm of cumulative social and academic failures associated with untreated ADHD. To reduce overall impairment, as well as control core symptoms, comorbid conditions must be addressed and treatment optimized.

You can help the adolescent with ADHD by obtaining an accurate diagnosis and determining which treatments are best for that individual, based on the duration, intensity, and range of ADHD symptoms; comorbid conditions; and associated impairments. Ultimately, the adolescent will learn to anticipate difficult environments and situations and make informed educational, social, and vocational choices.

ACKNOWLEDGMENT

The authors thank Rowena Hughes and Gillian Wain for editorial assistance in preparing the manuscript of this article.

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37. Greenhill LL: Efficacy and safety of OROS MPH in adolescents with ADHD. Presented at 49th Annual Meeting of the American Academy of Child and Adolescent Psychiatry, San Francisco, Calif., October 22–27, 2002

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DR. STEIN is professor of psychiatry, section of child and adolescent psychiatry, department of psychiatry, University of Chicago. He is a paid consultant for McNeil Pharmaceuticals, Eli Lilly & Co., and Novartis. He serves on speaker's bureaus for McNeil Pharmaceuticals and Eli Lilly & Co. and on the advisory board of McNeil.

DR. BAREN is a consultant in behavioral and developmental pediatrics in Orange, Calif., and clinical professor of pediatrics at the University of California at Irvine School of Medicine. He is a consultant for McNeil Consumer and Specialty Pharmaceuticals, Colwood Healthworld, and Shire Pharmaceuticals. He serves as a speaker for McNeil Consumer and Specialty Pharmaceuticals and a speaker and faculty advisor for Shire Pharmaceuticals.

The authors received editorial assistance in preparing this article from Colewood Healthworld.

Stimulants: Is abuse a danger?

The potential for abuse of stimulant medication is a concern that applies particularly to adolescents, as is evident from the numerous stories that have appeared in the lay press about adolescents who abuse methylphenidate (MPH) or dextroamphetamine by injecting it or taking it intranasally to produce a "high." Although such abuse does occur, it is not a common phenomenon; according to a 2002 report of the General Accounting Office, diversion of stimulants to others is a far bigger problem than stimulant abuse by patients.¹

Long-acting stimulants minimize both of these risks. Once-daily administration means that the medication can be given at home under parental supervision and need not leave the house, thereby limiting opportunities for diversion. Moreover, the MPH in the Concerta tablet is in a paste form that cannot be ground up or snorted.²

Another concern about stimulants is that the use of MPH to treat ADHD increases the risk of substance abuse later in life. Long-term follow-up studies do not support this concern, however.³ In fact, several recent studies suggest that treatment with stimulant medication diminishes the risk of later substance abuse by children with ADHD.^4–6 Stimulant treatment also can be expected to reduce the risk of early nicotine dependence in adolescents with ADHD, as many studies have noted.^7,8

REFERENCES

1. General Accounting Office: Attention Disorder Drugs: Few Incidents of Diversion or Abuse Identified by Schools. Washington, D.C., United States General Accounting Office, 2001

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5. Paternite CE, Loney J, Salisbury H, et al: Childhood inattention-overactivity, aggression, and stimulant medication history as predictors of young adult outcomes. J Child Adolesc Psychopharmacol 1999;9:169

6. Wilens TE, Faraone S, Biederman J, et al: Does stimulant therapy of attention deficit hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature. Pediatrics 2003;111:179

7. Milberger S, Biederman J, Faraone SV, et al: ADHD is associated with early initiation of cigarette smoking in children and adolescents. J Am Acad Child Adolesc Psychiatry 1997;36:37

8. Lambert NM, Hartsough CS: Prospective study of tobacco smoking and substance dependencies among samples of ADHD and non-ADHD participants. J Learn Disabil 1998;31:533

 

Mark Stein, Martin Baren. Welcome progress in the diagnosis and treatment of ADHD in adolescence. Contemporary Pediatrics August 2003;20:83.