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Editor's Note:

The diagnosis and treatment of attention-deficit/hyperactivity disorder (ADHD) in adolescents and young adults is an active area of research. The definition of the disorder is even undergoing revision to acknowledge the limitations imposed by prevailing diagnostic criteria. With the proliferation of new medical and psychosocial treatments for ADHD, clinicians have many options for helping adolescents and adults manage their impairments. To put these developments into perspective, Medscape's Randall F. White, MD, FRCPC, spoke with Stephen V. Faraone, PhD, Professor of Psychiatry and Director of Child and Adolescent Psychiatry Research at the State University of New York, Upstate Medical University, in Syracuse, New York.

Medscape: The persistence of ADHD into adolescence and adulthood is well recognized by clinicians, but how do the manifestations of the disorder shift during the teens and twenties?

Dr. Faraone: I would dispute that it's well recognized, although it's becoming more well recognized. My experience is that many people don't understand that the disorder persists; although the obvious symptoms of hyperactivity and impulsivity tend to wane over time, the symptoms of inattention continue. The ADHD adult is more inattentive and much less hyperactive and impulsive than the ADHD child. Sometimes this remission in symptoms is confused with a remission of the disorder. It's not uncommon for an adult patient with ADHD to come into clinic and, at the time the doctor is talking to him or her, not fulfill the full DSM criteria for ADHD. When one does a careful history, one can confirm that the patient has had all the manifestations. This is true for some adolescents too. The technical diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) is ADHD in partial remission because the DSM acknowledges that the disorder in adults may take on this less severe profile.

Medscape: What are the most significant functional impairments that clinicians should look for in these patients?

Dr. Faraone: ADHD is a chronic and pervasive disorder, so it affects the patient's life in a pervasive manner. If a patient has only one area of impairment, such as marital discord, but is functioning well at work, you'd wonder whether the problem really was ADHD because it doesn't go on hold during work hours -- it's constantly there. So you typically find difficulties in relationships and at work, but this doesn't mean the affected person can't achieve well. One has to look at the patient's occupational achievement in the context of intellectual abilities. Someone who is very intelligent won't do as well as he might have otherwise, but this is difficult to assess.

If a patient is a lawyer with a legal practice that is doing reasonably well, some doctors might say, "You can't have ADHD; if you had ADHD, you'd never be able to be a lawyer." That's not true. ADHD occurs at every level of intelligence. My colleague Joe Biederman and I have published research showing that at every level of educational attainment, adults with ADHD are doing worse occupationally than adults who don't have ADHD.[1] For instance, an adult with ADHD who got A's in high school makes less money than an adult without ADHD who also got A's.

Medscape: The standard of care now entails prescribing a long-acting psychostimulant for children with ADHD. Are the considerations in pharmacotherapy any different among young adults?

Dr. Faraone: There are some differences, but the main point is that the effectiveness of medication is the same for children, adolescents, and adults. Stimulants have high efficacy,[2,3] and nonstimulant medications have moderate but still good efficacy.[4] Most of the popular medications, such as methylphenidate, amphetamines, and atomoxetine, have been studied in all age groups. One difference would be risk for abuse. Eight-year-olds do not abuse drugs, and we don't worry about their abusing drugs. Their parents have control over the medication. On the other hand, teenagers are entering the age of risk for drug abuse, and adults are in that risk period. One has to do a very careful assessment of patients' substance-use history.

That said, although the stimulants are abusable, the problem is less severe nowadays because long-acting stimulants are less abusable than short-acting stimulants. The reason is that it's easy to take an immediate-release amphetamine or methylphenidate tablet, grind it up, and obtain a form to snort or inject to get high. By contrast, with an OROS methylphenidate pill, it's much more difficult to extract the stimulant. Because of that, these formulations are much more resistant to abuse. The pharmacokinetics of drug delivery of the intact pills also have an effect on abusability of the medication. The ratings of euphoria are much lower with OROS methylphenidate than with immediate-release methylphenidate.[5]

Another consideration is that stimulants cause a small increase in blood pressure.[6] In children, this is almost never an issue because they are not vulnerable to developing hypertension. Among adults, a substantial proportion will have undiagnosed borderline hypertension, so doctors prescribing stimulants to adults need to monitor their patients' blood pressure.

Medscape: Children usually take medications because adults administer them, but teenagers and young adults gain autonomy and move away from home. Does treatment adherence become more of a problem?

Dr. Faraone: Adherence is a huge problem in all of medicine, and the question as to whether it gets worse for adolescents and adults is interesting. I think there is a greater risk for nonadherence for 2 reasons. One is that adolescence is a time of rebellion, when individuals may do what they want and not what the parent or the doctor wants. It's not uncommon for adolescents to refuse medication because they don't like the side effects and they don't care if their school work suffers. That is less observed in younger kids, who are more likely to take medication because their parents want them to and parents can guarantee compliance. Although there are no real data, that is the sense we have from clinical experience.

The second concern is that an adult with ADHD may be disorganized and inattentive, and so may forget to take the medication and even forget to go to the doctor. That is another reason that long-acting medications are important. Having to take medication once a day is much less a strain on the memory than having to take it 2 or 3 times a day.

Medscape: How can the clinician create a good therapeutic alliance with patients in this age group in order to improve treatment adherence?

Dr. Faraone: There's nothing unusual in creating the alliance with the ADHD patient compared with other patients. One has to use the usual clinical skills, show empathy for the patient, and understand the patient's particular profile of strengths and weaknesses. Helping patients understand how the medication helps them is probably the best way to maintain adherence. The therapeutic alliance is very important; lots of research shows that the best predictor of outcome in any kind of therapy is the patient's rapport with the therapist.[7]

Medscape: The DSM-IV requires that symptoms of ADHD present before age 7 as a criteria for the diagnosis. You have done research on adults who have ADHD symptoms with onset later than 7 years of age. What proportion of adolescents and adults may have a late onset?

Dr. Faraone: I prefer to think of it as the proportion that reports a late onset or in which one can't establish the age of onset. In many cases, you don't really know when the onset occurred. Late onset is fairly common, but I don't know of any good data. I would estimate it to be about 20% to 30%, but it would vary a lot with the clinical setting. We'll be able to look at this question in a study under way in which we have followed people over their lifetime beginning in childhood.

Medscape: What have you learned about these patients?

Dr. Faraone: We took a rigorous approach to develop the late-onset diagnosis. We said to ourselves, "If these people have ADHD, they should show a clinical profile similar to people who clearly have full-criterion ADHD." Their neuropsychological profile does show executive-function deficits just as in adults who have early-onset ADHD,[8] and they show a similar pattern of psychiatric comorbidity.[9] It's very common for adults with ADHD to have a history of antisocial disorders, substance abuse, high rates of smoking, and depression.

We wondered initially whether late-onset adults just had milder cases, but there's no particular evidence for that. They're at risk for similar kinds of impairment. For example, increased risk for traffic accidents is a hard measure of impairment.[9] The profile of substance-use disorders is very similar in early- and late-onset ADHD. Perhaps most important from my point of view as a potential biological validator is that in relatives of late-onset patients you find a high prevalence of full-criterion ADHD.[9] It's just about as high as you see in the relatives of patients with full-criterion ADHD. That suggests that it is indeed the same disorder because it runs in families in the same way.

Remember, the age-onset criterion for ADHD in DSM-IV is based on clinical wisdom and on the belief that ADHD is a childhood-onset disorder. At the time, there were no data to establish the age cutoff. Any study that has looked at this issue has found that ADHD with late onset, particularly up to about 12 years of age, seems to be as valid as early onset.

Medscape: Does obtaining collateral information from family or acquaintances of young adults improve diagnostic reliability?

Dr. Faraone: In many cases no collateral informants are available. The good news is that research shows that one can make the retrospective diagnosis in a valid manner even when you don't have informants. If informants are available, they can improve diagnostic accuracy. This was best seen in a study by Barkley[10] of children with ADHD whom he followed into adulthood. He looked at self-report vs parental report of ADHD, and he found that informant reports were better predictors of impairment than self-reports. His conclusion was that patients had lack of insight into how the disorder affects them. In some cases, one may miss the diagnosis of ADHD because of this poor insight on the part of the patient.

Medscape: Joseph Biederman and colleagues[11] recently completed an open-label, uncontrolled, 6-week study of OROS methylphenidate in adults with late-onset ADHD. What were the findings?

Dr. Faraone: I'm very familiar with that study. The medication was efficacious, which is further support for the idea that these are true cases of ADHD. The people enrolled had substantial signs of the disorder, even though it was ADHD with a late onset. The sample size wasn't that large. Most ADHD trials are 4-6 weeks because, particularly with stimulants, you can see a clear effect in 4 weeks.

Medscape: What is the next step in confirming the treatment response in this population?

Dr. Faraone: I see 2 next steps. One is to have a larger placebo-controlled trial to get a better estimate of the size of the effect. The second step would be a longer-term open-label trial to see what happens over time to people with late-onset ADHD treated with stimulant medication.

Medscape: Have studies been carried out on psychosocial interventions for ADHD in adolescents and young adults?

Dr. Faraone: Psychosocial treatments for older patients are less well studied. We know a lot about youth, such as in teaching parents behavioral management training, but those therapies aren't typically used in adolescents. Safren and colleagues[12] at Massachusetts General Hospital have looked at supplementing medication with cognitive behavioral therapy (CBT) for ADHD. They have devised an ADHD-focused program that's aimed at helping adults get organized, understand the nature of their symptoms, and learn how they can compensate.

The initial work looks very promising. They showed that with medication plus CBT, greater symptom reduction occurs than with medication alone. Note that all of these patients are treated aggressively with medication. Dr. Safren has a grant to study this further, and we'll be learning more about this therapy in the future.

Medscape: What psychosocial interventions for ADHD do you recommend to clinicians who have limited access to specialized services?

Dr. Faraone: In the ideal situation, the general clinician would start with medication and treat the patient appropriately. In the early 1990s, it was thought that stimulants don't work for adults with ADHD because physicians used the same doses as in children. Spencer [13]did studies showing that when adults are treated with higher doses, you see higher levels of efficacy. We subsequently published a meta-analysis of all of the studies of methylphenidate, and found that those that used high doses showed a strong effect and those that used low doses showed a weak effect.[14] Clinicians who are timid about dosing will see a limited response.

Assuming that a patient is dosed appropriately and that if one medication fails another is tried, it would make sense to refer the patient for CBT if residual symptoms are present. The problem the clinician will face is that few people are trained for ADHD-specific CBT. But a cognitive-behavioral therapist who is at least familiar with the diagnosis of ADHD would probably do the patient a world of good. In general, insight-oriented psychotherapy is not helpful for ADHD. These patients need practical therapies to help them deal with the real world.