Clinical Supplement

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Pediatric ADHD: Clinical Criteria for Diagnosis and Management

Timothy E. Wilens, MD; Floyd R. Sallee, MD, PhD, Dennis J. Rosen, MD James M. Swanson, PhD, James McGough, MD Michael J. Manos, PhD

Moderator: Peter L. Salgo, MD
Section editor: David L. Ginsberg, MD

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 Primary Psychiatry. 2004;11(2):1-10

 

CME accredited monograph of an adapted analysis of a Medical Crossfire© educational initiative

Funding for this supplement has been provided through an unrestricted educational grant by Shire US


Faculty Affiliations and Disclosures

Dr. Wilens is associate professor of psychiatry in the Department of Psychiatry at Massachusetts General Hospital and at Harvard Medical School, both in Boston.

Disclosure: Dr. Wilens is a consultant to, serves on the speakers’ bureaus of, and/or receives grant/research support from Abbott, Celltech, Eli Lilly, GlaxoSmithKline, McNeil, NIDA, NIMH, Novartis, Pfizer, and Shire.

Dr. Rosen is a developmental pediatrician at the Wing Memorial Hospital at the University of Massachusetts Memorial Health Care in Worcester.  
         
Disclosure: Dr. Rosen is a consultant to McNeil and Shire; serves on the speaker’s bureaus of Celltech, Eli Lilly, McNeil, Novartis, and Shire; and receives honorarium/expenses from Celltech, Eli Lilly, McNeil, Novartis, and Shire.

Dr. McGough is associate professor of clinical psychiatry in the Division of Child and Adolescent Psychiatry at the David Geffen School of Medicine, University of California, in Los Angeles.

Disclosure: Dr. McGough is a consultant to Cephalon, Eli Lilly, McNeil, Novartis, and Shire; serves on the speaker’s bureaus of Eli Lilly, McNeil, Novartis, and Shire; and has received grant/research support from Boston Life Sciences, Cephalon, Eli Lilly, Janssen, McNeil, NIMH, Novartis, Pfizer, Shire, and Targacept.

Dr. Sallee is professor of psychiatry and pediatrics and vice chair of the Department of Psychiatry at the University of Cincinnati College of Medicine. He is also director of the Pediatric Pharmacology Research Unit, Division of Child Psychiatry, and Division of Pharmacology Research at Cincinnati Children’s Hospital Medical Center in Ohio.

Disclosure: Dr. Sallee is a consultant to Bristol-Myers Squibb and Otsuka; serves on the speaker’s bureaus of Eli Lilly and Pfizer; and has received grant/research support from Bristol-Myers Squibb, Eli Lilly, Pfizer, and Shire.

Dr. Swanson is director of the Child Development Center and professor of pediatrics and cognitive science at the University of California, Irvine. He is also senior fellow at the Sackler Institute, Weill Medical College of Cornell University, in New York City.

Disclosure: Dr. Swanson has been a consultant to, served on the speaker’s bureaus for, and received grant/research support from Celltech, Cephalon, Eli Lilly, Gliatech, Janssen, McNeil, Novartis, and Shire.
Dr. Manos is director of the ADHD Center for Evaluation and Treatment (ACET) Division of Pediatrics at the Cleveland Clinic Foundation and is also on medical staff at the Children’s Hospital in Cleveland, Ohio.

 

Disclosure: Dr. Manos is a consultant to Shire; serves on the speaker’s bureaus of Eli Lilly, McNeil, and Shire; and has received grant/research support from Noven and Shire.

Focus Points

Review the clinical impact and diagnostic criteria of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, as well as current diagnostic challenges.

Discuss the comorbid psychiatric conditions often encountered with ADHD and their effect on management.

Describe the role and effectiveness of behavioral interventions in the management of ADHD.

Discuss the role of nonpsychostimulant agents and compare the currently available psychostimulant medications for ADHD.

Abstract

The diagnosis and management of pediatric attention-deficit/hyperactivity disorder (ADHD) are surrounded by puzzling debates and controversies. Although ADHD remains the most commonly diagnosed behavioral disorder in childhood, questions persist in some circles concerning the medical validity of this syndrome. Prevalence estimates of ADHD vary, shaded by methods of ascertainment, diagnostic criteria, informants, and population sample. Symptoms may be developmental in course and change their presentation with age, often presenting diagnostic dilemmas. In addition, psychiatric comorbidities often complicate the clinical picture. Although behavioral approaches are considered an important component of a treatment plan, the effectiveness of specific psychosocial therapies continue to be debated. The role of nonstimulants needs to be further defined, and differing perspectives remain regarding the appropriate selection and use of stimulants, which are considered first-line therapy for ADHD.

 

Timothy E. Wilens, MD

Prevalence and Recognition

According to the Centers for Disease Control and Prevention ~8% of American children have attention-deficit/hyperactivity disorder (ADHD), ~50% of ADHD children remain undiagnosed, and 50% of diagnosed children are untreated.1 Thus, despite claims of overdiagnosis, ADHD remains underdiagnosed. ADHD, which has been dismissed as an “American illness” for many years, is seen in virtually every culture studied. There are extraordinarily strong data to support its occurrence worldwide. Despite the claims of those who say ADHD is simply a manifestation of overzealous physicians or representative of poor parenting, as physicians the onus on us is preventive—to identify the illness early, treat it, and reduce the sequality of the disorder over time.

Several studies of school-age children showed the presence of ADHD symptomatology during the preschool years. In general, one can extend the diagnostic criteria for school-age children to preschoolers. Among those with ADHD, hyperactivity and impulsivity tend to diminish somewhat over time, whereas attention symptoms persist. While there are claims that ADHD diagnoses are not accurate because they are often made by report, psychiatrists have always had confidence in this form of diagnosis. For example, both panic disorder and depression are diagnosed by report. Moreover, parents tend to be good reporters of their child’s psychopathology.

Overlapping symptoms may confuse the differentiation of ADHD from another condition. What is more concerning, however, is the omission of the comorbidity diagnoses. Data show that, in the majority of patients with ADHD, two or three disorders occur simultaneously. Comorbidity has an effect on treatment; for example, certain classes of medicine may result in an exacerbation of mood symptoms in the patient with prominent mood symptoms associated with ADHD. In this case, one would first treat the mood disorder and then focus on treating the ADHD. Reverse comorbidity is very important as well. There are high rates of ADHD among patients who present with a diagnosis of another psychiatric disorder. For example, 20% of adults with depression have ADHD. It is important to clarify what conditions are present initially and then devise a hierarchical treatment rank.  

Pharmacotherapy for ADHD

Nonstimulants

The nonstimulant medications work largely through the catecholaminergic system, including noradrenergic or dopaminergic effects. In 2002 the Food and Drug Administration approved atomoxetine (Strattera), the first nonstimulant for use in ADHD across the life-span. Michelson and colleagues2-4 conducted several studies indicating that atomoxetine was better than placebo in reducing ADHD symptoms and improving social and family functioning. In clinical trials, atomoxetine was not associated with serious adverse events and there were few discontinuations for adverse events.5 Head-to-head studies are ongoing, and atomoxetine may be particularly useful in situations where stimulants may exacerbate symptoms such as comorbid tics, or where there is a significant amount of anxiety or depressive symptomatology. Atomoxetine may also be useful in cases where stimulants fail.

Other nonstimulant medications include tricyclic antidepressants, which have been used since the 1970s, and bupropion. Data show that atypical antipsychotics are not useful for core ADHD symptoms, and subjecting children to this very significant class of agents is typically not necessary for the treatment of this condition. 

Stimulants 

There has been a concern at a preclinical level that stimulants can cause substance abuse. However, children who are not treated for ADHD have twice the risk for substance abuse across the life-span. We conducted a meta-analysis6 of all long-term published studies in which treated and untreated youths with ADHD were followed for substance-use disorders. More than 1,000 children were followed for a mean of 12 years. We found that stimulant use did not increase the risk for substance abuse, rather it reduced the risk for substance abuse by 50%. While stimulant therapy does not immunize against the potential for substance abuse, it may reduce the risk to that of the population without ADHD.

Herbal Remedies

Some parents request that the physician suggest something “natural” for their ADHD child rather than a pharmaceutical agent. However, just because something is natural does not mean it is safe: cyanide, arsenic, and strychnine are all natural compounds. In addition, pharmaceuticals undergo rigorous testing for both efficacy and safety. Naturally occurring compounds often are not tested for safety, are not even tested for true efficacy, and may result in drug interactions that affect the metabolic pathways. Concerned parents should be informed that stimulants and bupropion, medications used for ADHD, have chemical structures similar to the naturally occurring neurotransmitters dopamine and norepinephrine. Moreover, the agents we use to treat ADHD work with the natural machinery of the brain presynaptically, affecting dopamine and norepinephrine and improving the function of affected neurons. They appear to normalize the chemistry to produce an outcome.

It is very important for practitioners to confront this issue with parents and realize that there is a liability when recommending natural treatments. Some herbal agents demonstrate potent inhibition of the P448 system as well as monoaminoxidase inhibition, which we know has widespread application in terms of drug-drug interactions. There may also be absorption problems, chelation problems, and real medical issues.
 

Dennis J. Rosen, MD

Diagnosis and Management

There are many children who should be evaluated for ADHD but are not. Often, parents of these children are not knowledgeable about assessment procedures, do not have an appreciation or understanding of ADHD and its treatment, or are in denial about the presence of the disorder in their children. The rate of diagnosis can be improved through community education initiatives such as educating healthcare providers, teachers, social workers, and mental health professionals. These professionals can then refer appropriate children for an initial diagnostic evaluation with the child’s primary care provider (Slides 1a, 1b).7

Most children display significant core symptoms of inattention and/or impulsivity and hyperactivity. Reports from parents and teachers provided in the form of rating scales available at the American Academy of Pediatrics (AAP) Web site (www.aap.org) form the basis with a complete history and physical exam for evidence-based diagnosis. The recently published ADHD: A Complete and Authoritative Guide8 (including a smaller pamphlet called Understanding ADHD) is now available and includes guidelines for treatment with both behavioral management strategies and medication (Slide 2). Direct contact with teachers can be helpful if possible and direct input from students by interview and rating scale is often helpful.

Ultimately, successful management of ADHD is defined as improvement in core symptoms toward normalization. Keypoints in the guidelines include recognizing ADHD as a chronic condition; collaboration between school personnel, family, and clinician for target outcomes; stimulant medication and/or behavioral therapy; and reassessment evaluating for coexisting conditions in the presence of failure to meet target outcomes on systemic follow-up.

The Role of the Primary Care Physician

Primary care physicians (PCPs) are in the best position to identify ADHD and to develop appropriate tools and strategies for identifying comorbid symptomatology.9 The AAP does not support blood work or x-rays in this regard and neuroimaging and genomic/genetic testing will not be available for many years given limited sensitivity and specificity. Rating scales, interview techniques, and thoroughness of a database from both school and home form the most effective means to clarify diagnosis and monitor treatment effects. Pediatricians’ unique understanding of the family history is critical in defining the possible presence of inherited affective disruptive or comorbid learning disability symptoms.

Alternative Therapy

Stimulant medication and occasionally use of careful nonstimulant medication remain the treatments of choice for ADHD, but many parents remain skeptical and influenced by alternative literature and “natural therapies.” Recent literature10 suggest that parents prefer alternative treatments because they are natural and provide them with “more control over treatment.” Although 54% of parents reported their use, only 11% of the parents shared this information with the child’s physician. Kemper’s11 book The Holistic Pediatrician, and an article by Chan and colleagues12 outline responsible limitations and dangerous side effects of alternative therapies as well as the absence of double-blind, placebo-controlled studies. They also provide specific parent handouts which are available for pediatricians’ use.

Stimulants: Treatment and Adverse Effects

Short, intermediate, and long-acting agents are now available as pumps, patches, and beads, in the smorgasbord of medication treatments with stimulants. A critical developmental question relates to the child’s swallowing capabilities and the number of hours a day treatment is considered. In general, short-acting agents can be abused and have doubled in street value in the last 4 years, particularly in college communities. The safety and efficacy of hard-to-abuse intermediate and long-acting methylphenidate and mixed amphetamine salt products make them highly advantageous, with traditional side effects including insomnia, anorexia, and rebound/mood lability. A careful history and premedication of these potential side effects helps to clarify both the quality and quantity of their presence and establish reasonable treatment alternatives. The most common reason for treatment failure remains poor compliance. Dysphagia or difficulty swallowing without a neurological basis is only occasionally disclosed and is often a manifestation of anxiety and/or posttraumatic symptomatology.

Middle- and high-school students often need control beyond 10–12 hours to address homework concerns post extracurricular activities.13 If behavioral strategies do not work in these situations (though they often allow for a lesser dose of stimulant according to the Multimodal Treatment of Children With ADHD study14) augmentation may be necessary in the afternoon and early evening either with a shorter-acting stimulant, a half dose of a longer acting agent, or a nonstimulant, ie, guanfacine, atomoxetine, or a selective serotonin reuptake inhibitor, depending on which comorbidity is identified.

Multimodal Treatment

Multimodal therapy continues to be the most responsible and thorough approach to treatment both for primary ADHD symptoms and associated side effects, such as insomnia. For more information, the physician is referred to the work of Gardiner and Kemper.15

James McGough, MD

A Biological Condition

Although there is plenty of hard medical evidence that ADHD is a real disease, some say it is a product of modern society or poor parenting. However, medical descriptions of ADHD that date back 140 years have recognized it as a brain-based condition. There was an exception to that in the 1960s where virtually everything was being blamed on poor parenting. We now know that there are genetic contributions to ADHD that are about as strong as genetic contributions to height. In fact, the evidence for a genetic link is much stronger for ADHD than for schizophrenia and many other psychiatric conditions. Many research groups around the world have identified the same genes as risk factors for the disorder.16,17 In addition, we have neuropsychological information that is consistent with pharmacologic response in terms of areas of the brain that are affected. And we have neuroimaging studies that show clear brain differences in both children and adults irrespective of whether the children were medicated or not. The evidence supporting ADHD as a biological condition is probably as strong or stronger than that for any other condition in psychiatry.

The Clinical Diagnosis

ADHD is a clinical diagnosis based on clinical criteria, just as headache is a clinical diagnosis. If properly trained clinicians use the same criteria, they will pick out the same child as having ADHD 90% to 95% of the time. Many parents want to be reassured about the accuracy of a diagnosis through neuroimaging, but although the brain scan formation is fascinating from a research point of view, there is no clinical evidence to support its diagnostic use. In addition, there is no psychological testing for ADHD itself, although there are comorbid conditions of ADHD, eg, a learning disability, that can be ruled out with psychological testing.

Although some claim there are diagnostic differences in gender and ethnicity among children with ADHD, the issue of access to health care cannot be overlooked. Savvy, upper-middle-class parents tend to obtain care for their children. Less-savvy parents with fewer resources often do not know to get care, and this is where disparities show up.

The Art of Medicine

Primary care physicians (PCPs) and pediatricians may not be particularly well versed in the area of psychiatry. However, physicians dealing with ADHD must address comorbidity including learning disabilities, oppositional defiant disorder, conduct disorder, depression, anxiety, and substance abuse and nicotine use in older children. While this is hard to do in a 12-minute consultation, the reality is that ADHD must be dealt with in the HMO (health maintenance organization) situation. In keeping with the art of medicine, PCPs who are savvy and who keep informed become good at this.  

Although 70% of ADHD patients have two or more conditions, there is little research on comorbidity in ADHD. Treatment decisions are therefore largely based on clinical experience. In deciding which condition to treat first, the physician should assess the individual patient and decide where the impairment is. For example, if a person has a severe depression or anxiety, or bipolar disorder, it would be really foolish not to address that first. I would begin with treatment of the comorbid issue that is most life-threatening.

The Stimulant Agents

There is nothing on the market that works better than a stimulant. The development of longer-acting compounds, which are effective for 8–12 hours, provide many advantages. The greatest advantage is the lack of social stigmatization; because long-acting compounds can be administered in the morning, children do not have to suffer the embarrassment of going to the school nurse for their medication during the day. Other advantages include increased compliance and the elimination of controlled substances within the school setting. The downside to the longer-acting compounds is that they may not work long enough for patients in whom the work or school day is longer than 8–12 hours.

In general, my advice to clinicians is to prescribe a 12-hour compound, although there are reasons to scale back to an 8-hour compound in some children. Choosing between two long-acting drugs is a matter of evaluating the individual patient. Methylphenidate (Concerta) is probably a little gentler. Mixed amphetamine salts (Adderall) is stronger, more flexible, and is contained in capsules that can be broken open and sprinkled. However, treatment is individualized and one cannot predict who is going to respond better to which agent.

Alternative Treatment

Successful management of ADHD in children includes a decrease in symptoms or an improvement in the quality of life. However, with the exception of antibiotics for viral colds, most parents do not want their child on medication, so there is a market for “natural” medication. Besides the fact that some of these treatments are dangerous, what is often missed is that having ADHD is dangerous. By not giving a medication that has been well tested and tried, you are increasing the time during which the child grows up having negative developmental experiences and not getting proper treatment. The child thereby becomes subjected more often to peer rejection; school failure; involvement with drugs, sex, and alcohol; and other serious consequences. Thus, failing to give medications that are known to be effective is really detrimental to the children. In fact, several authorities have stated that the evidence supporting the use of approved medicines for ADHD is so strong that a clinician who does not address this issue is probably being negligent.

 

 

Floyd R. Sallee, MD, PhD

Diagnostic Challenges

Many children presenting to the emergency room are victims of accidents both in the home and on the street, and these accidents are often associated with unrecognized ADHD. There are also serious consequences for children who are kicked out of preschool for aggressive behavior without receiving medical follow-up to screen for ADHD.

The ADHD diagnosis is complicated by comorbid conditions. It is more likely than not that an individual with ADHD will also have one or more other disorders. These disorders vary along a continuum as the individual grows older; for example, what may have been an oppositional defiant disorder comorbid with ADHD may develop with advancing age into conduct disorder and/or substance abuse disorder. The most common comorbidities are learning disabilities as well as anxiety and depressive disorders.

ADHD as a comorbid condition can complicate diagnoses of other disorders as well. For example, an adult may present with a diagnosis of major depression and the physician may not appreciate the fact that the patient has ADHD. The depression may not remit or even respond to treatment until the ADHD comorbidity is addressed.

A New Role for Specialty Clinics

The role of some specialty clinics is to help primary care providers (PCPs) with problematic ADHD patients and then return the patients to the primary care practice. The role of clinic is, therefore, not so much to help with diagnosis as to manage the more difficult patients, most of whom have comorbid conditions. The problem is not that pediatricians or PCPs do not recognize comorbidity, but that they need assistance in making broader assessments and providing additional therapies. For example, I run a consultation care clinic in Cincinnati, Ohio, where we have agreed to take all the problematic ADHD patients out of certain pediatric practices, help them with treatment, and then return them to the practice. The idea is to help pediatricians manage more difficult patients, which are usually those with comorbid conditions. While the pediatricians recognized that there was something different about the patient, they could not pinpoint and needed a little bit of extra assistance in making a broader assessment of the patient and figuring out what additional therapies should be used. In treating those patients with comorbid conditions, I would begin treating the impairment first, regardless of diagnosis.

Treatment Management

Behavioral Therapy

Some data, such as that of the Multimodal Treatment of Children with ADHD study (MTA),18 and Pelham and associates,19-21 suggest that clinicians can use fewer medications or less medication if behavioral therapy is included in the management strategy. Clinicians have the ability to reduce total medication and to achieve effectiveness at times when the medication may not be working for a particular patient. However, most of the effective treatments for ADHD elevate catecholamines in the brain. This is not to say that catecholamine disturbance is the reason for ADHD, but all of the effective agents seem to increase both dopamine and noradrenaline in certain brain areas associated with executive functioning and attentional factors.

Stimulants 

There are literally thousands of studies in just the past few years supporting the use of stimulants to mitigate the symptoms of ADHD. These studies are usually double blind and placebo controlled. There are no credible head-to-head comparisons of stimulants. Although studies have firmly established the superiority of stimulants in the treatment of ADHD, most of them are short term, meaning usually no longer than 8–12 weeks in length. Very few are as long as the 18-month MTA study. Thus, while the stimulants are considered the gold standard, there are some deficits in our knowledge of stimulant use, eg, the range of symptoms affected and the long-term outcomes.

The safety factor of stimulants is one point that cannot be argued; there is probably no safer class of medications used in pediatrics than the stimulants. The most common adverse event of stimulants is loss of appetite; there may also be nuisance side effects like headache, mood changes, and change in sleep patterns. Individuals with ADHD often demonstrate poor sleep patterns and poor sleep quality, and it is unknown and highly individualized whether stimulants in certain individuals might improve or worsen the problem.

The Nonstimulant Agents

The nonstimulant agents cannot really be lumped together, because of the variance in efficacy rates among them. For example, clonidine has a response rate of ~40%, meaning that ~40% of patients treated with clonidine will have an improvement in ADHD symptoms, whereas the response rate for a stimulant is ~70%.

 

James M. Swanson, PhD

Diagnostic Challenges

Because ADHD is a disorder identified through subjective criteria, the diagnosis can be difficult, particularly for preschool children. A diagnosis of ADHD requires the manifestation of behavior that is developmentally inappropriate; the range of developmental progress is broader in preschool children than in other age groups as to make appropriateness a difficult determination. Furthermore, in preschool ADHD treatment programs teachers are reluctant to identify children as having psychopathology or deviant behavior, even when the children are very disturbed. Most of the diagnostic information does not come from the physician’s direct observation of the child; rather, it comes from subjective reports of parents and teachers, among whom there is often disagreement.  

Identifying those preschoolers whose symptoms will persist can be problematic. While children who are aggressive at school age probably were aggressive as preschoolers, Campbell and colleagues22-24 showed that preschool children with symptoms and behaviors associated with ADHD often lose them in elementary school. That goes for aggressive behavior, oppositional behavior, and symptoms of ADHD. An ongoing research study, the Preschool ADHD Treatment Study (PATS), is currently evaluating this issue. 

While there are often comorbidities with ADHD, physicians should be aware that symptoms often interpreted as comorbid conditions can actually be consequences of ADHD itself.18 ADHD may present with anxiety symptoms or symptoms of demoralization or depression, for example, and with treatment of ADHD these so-called comorbid conditions that are actually symptoms of ADHD resolve. The Multimodal Treatment of Children with ADHD study found that after 14 months of treatment of ADHD symptoms, the high rates of comorbidity were cut in half.

How the Stimulants Work

The impetus for the development of the first sustained-release preparation of methylphenidate, Concerta, was the discovery that acute tolerance to the use of methylphenidate and amphetamine develops each day. A higher concentration of the drug in the afternoon and the morning is needed to maintain the effect. The once-a-day dosing form of methylphenidate produces a higher level in ascending pattern across the day, maintaining the effect for 10–12 hours. 

Unlike Concerta, which uses an osmotic pump delivery, the next sustained-release methylphenidate, Metadate CD, relies on a coated beaded technology in which 30% of the beads are not coated and thus release the drug immediately; the other 70% are coated with a polymer that, as it is broken down, releases the drug 2 or 3 hours after the pill is swallowed. Ritalin LA also employs a double-beaded system with a 50:50 ratio of uncoated to coated beads.21

A sustained-release amphetamine, Adderall XR, also utilizes a 50:50 double-bead technology.25 However, the half-life of amphetamine is longer than that of methylphenidate; the immediate-release form of the amphetamines in Adderall XR therefore has a longer duration of action than methylphenidate. Adderall has two releases, initially and then 3 or 4 hours after ingestion, with a longer half-life. Whereas Metadate CD and Ritalin LA last ~8 hours, Adderall XR and Concerta last 10–12 hours.

Some clinicians choose a shorter-acting agent despite looking for a longer-acting effect because some parents and practitioners do not want children on medication when they do not need it. However, Adderall XR and Concerta, with 12-hour dosing, are probably the primary agents prescribed now. These drugs are not more effective than giving Ritalin three times a day or Adderall twice a day, but they do remove the stigma associated with taking the pill at school. Compliance is also increased because the patient only needs the medication once a day.

The stimulants are going to be hard to beat because they rapidly act, have a good effect, and are very safe. The long-term follow-up study as part of the MTA research will give firm evidence whether stimulants have an effect on growth over time. In the meantime, based on many small studies that have been done, the American Academy of Pediatrics, the American Academy of Child and Adolescent Psychiatry, and others have come to the conclusion that any adverse effects are temporary.

Behavioral Therapy

The MTA study,18 a 14-month, seven-site intervention trial in 579 children 7–10 years of age, randomized participants to four treatment strategies: medication alone; behavior therapy alone; a combination of medication and treatment; and community care. The goal of the study was to optimize behavioral treatment and compare it against medication. The intensive behavioral treatment program included intensive personal therapy, parent training, teacher consultations, daily behavioral report cards, and an 8-week summer treatment camp. At the end of the trial, children had poorer outcomes with behavioral therapy alone compared with medication alone or combination therapy. Behavioral therapy alone reduced symptoms to levels at which they were no longer defined as symptomatic in 34% of children. Therefore, although behavioral therapy is not as effective as drug therapy, it is certainly necessary to optimize symptom reduction and treatment effectiveness (Slides 3-5).  

Behavioral treatments that are available are not as effective as stimulant therapy. Equal amounts of work on developing both new medications and new behavioral treatments to optimize the management of children with ADHD are necessary.

 

Michael J. Manos, PhD

Diagnostic Differences

There is little mystery regarding the medical evidence for the diagnosis of ADHD. Even from birth, well-documented child temperament characteristics are evident. For example, children show easy, slow-to-warm-up, and difficult temperaments. A clinician who is informed about developmentally appropriate levels of natural, normal behavior can identify deviance at an early age, and it is certainly helpful to do so early to prevent issues such as violence and aggressiveness, for example. Children who show aggressive behavior in preschool are highly likely to show aggressive behavior in adolescence.

While ADHD is identified all over the world, differences in symptoms are evident in cultural expectations of behavior. This is shown in families who are immigrants to the United States. Children who are raised in the US by first-generation parents run into conflicts when behavior conflicts with natal norms and expectations. Research in Hawaii26 found that behaviors that would be considered normal in western culture are defined as deviant in other cultures. Symptomatic characteristics of ADHD are nevertheless evident across cultures.

Regarding differences among children with ADHD, sex is an interesting issue. There is a 3:1 ratio of boys to girls in childhood, but this ratio diminishes as age increases. In adulthood, the ratio of women to men is 1:1 in clinical settings.

Common symptoms of ADHD are generally prevalent across gender and ethnicity. The diagnostic criteria for ADHD are clear and allow consistent identification across cultures. The diagnostic process should include broad-band and narrow-band rating scales as well as a thorough semi-structured interview. In some cases, psychological testing can be helpful to rule out learning disabilities as a cause for inattention. Although some have suggested use of computerized structured interviews to diagnose ADHD (these are often used in research studies such as the Diagnostic Interview for Children), even a structured interview is not enough in and of itself to diagnose.

What is Attention?

Essentially, there are two kinds of attention. One kind is fascination, that is, something a person is intrinsically interested in. Fascination does not require medication or treatment to assist sustained attention. Individuals with ADHD use this kind of attention as well as anyone does. Directed attention, however, is the attention placed on a task that has to be done because it has a significant consequence to it; the task itself, however, is not interesting. A person would not be interested in the task but has to do it, like submitting one’s taxes every year, to avoid a negative result. The action of a stimulant improves directed attention where it is needed. In childhood, the primary problem is using directed attention in school-related tasks. There are many children who do absolutely great—perhaps even better than children without ADHD—when they are in an unstructured situation where there are few demands. However, when you put them in demand situations requiring directed attention, something that assists individuals to meet demand is needed.

Medication Noncompliance

Despite the fact that parents report that their children feel better when they take medication, noncompliance is often a problem. Swanson27 wrote a very interesting article on noncompliance with ADHD medication. He identified that compliance with a medication regimen was probably one of the most undervalued issues in successful management of ADHD. Education, that is, informing both parents and children of the usefulness of treatment, and the availability of long-acting medications make it much easier to treat pharmacologically.

In his review of compliance with stimulant medications in ADHD, Swanson27 noted that rates of noncompliance range from 20% to 65% in published studies. Factors contributing to noncompliance include inadequate supervision, inconvenience of multiple daily doses, the long-term nature of treatment, and reluctance of individuals to take medication due to social pressures or concerns about drug usage. Two approaches are likely to increase compliance with stimulant treatment: effective once-daily formulations and improved treatment information.

Quality of Life

While a primary goal of clinical work is to identify dysfunction and treat it, successful management of ADHD is more than a decrease in symptoms. Improvement in quality of life is important and rarely evaluated in treatment studies. In Bill Pelham’s summer treatment program, children are in a behavioral therapy treatment program for 7–8 weeks, 8:30am to 5:30pm daily. In this program, one participant’s mother commented that it was the first time in her life that she did not have to be startled when the phone rang, fearing a call requiring her to retrieve her misbehaving child. Whether or not behavioral intervention generalizes and makes a long-lasting difference or whether improvement using behavior therapy is better than medication alone is not the issue. The issue is that a parent’s perception of her relationship with her child can significantly improve.

 

Question & Answer Forum

 

Q: Is there any difference in how you treat patients with hyperactivity versus those with inattentive type?

 

Dr. McGough: The medications work equally well for both conditions. There are individual differences amongst all patients and sometimes some may do better on one versus the other, but there is really no way to know ahead of time.

Dr. Rosen: I have a subgroup of preadolescent female patients, who have fairly significant internalizing disorders, frequent developmental problems, and parent-child conflict, in addition to their ADHD inattentive type. They represent almost 20% of my patient population. I sometimes treat them not only with a stimulant but consider alternative treatments that might be nonstimulant in nature. There are also some preliminary studies to suggest that they may be better responders. We do not have enough data yet to be conclusive, but the key in such cases is that the stimulant is the best treatment for their attention-deficit disorder. The question is, diagnostically, is whether we are also dealing with comorbidity that is more subtle and hard to pick up.

Q: How often should a child who is being managed with a stimulant drug be followed?

 

Dr. Rosen: Target outcomes need to be reevaluated on a regular basis. As the child improves, that targeting reassessment can be expanded from every month to every 3 months to every 6 months. My biggest concern in my practice is that many children present having not been evaluated 1 or 2 years. And as they grow and change developmentally they have new dosing needs. They may not need a new dosage necessarily because of their height or weight, but because of new developmental challenges and comorbidities which warrant more regular follow-up. My personal feeling is that twice a year is very appropriate for follow-up of a child on stimulants.

Q: Are there any studies evaluating side effects of long-term use with stimulant and nonstimulant drugs?

 

Dr. McGough: There are studies of several years’ duration that assess safety. I think the safety data are actually very good. We also have 6 million prescriptions being written annually for the past 40 years. And if any major side effects occurred as a result of being on these drugs, epidemiologically that would have surfaced. So we do have studies of several years’ duration and a large epidemiological database showing that these medicines are safe.

Q: In the absence of psychotic symptoms or family history of bipolar disorder, how would you distinguish between bipolar disorder and ADHD?

 

Dr. Wilens: There is one major distinguishing factor, and that is mood. You will see severe mood lability with bipolar disorder. With ADHD, you may have some mild affective dysregulation, but that is all. In terms of the treatment, it is very important to address the bipolar disorder first. Get the mood stable with either a mood-stabilizing agent, such as an anticonvulsant or lithium, or an atypical antipsychotic, and then you can treat the ADHD.

Q: Are children self-aware enough to realize that they are having trouble? And do they report well enough to tell you that they are doing better once they are medicated?

 

Dr. Swanson: There is a difference of opinion on that. It depends on the age of the child. There is some evidence that children do have a hard time telling the difference when they are on medication and off medication. I did an earlier study in which I?asked children to determine whether they were on medication or off medication in a 2-day trial. Typically they could not tell the difference. They were much better on medication, but they were less concerned about their behavior. I am a psychologist, not a physician, so when the physician I work with is interviewing the parents, I?oftentimes talk to the children and ask them what they think about taking medication. The concern I have about embarrassment and stigma comes from asking children such questions. When I ask them if the medication makes them feel bad, they say no. And when I ask if it makes them do better, they say yes. However, when I ask them why they do not want to take the medication, they say it is because they are embarrassed. I think I can get that type of information from interviewing a child directly, doing some observation, and interacting with the child. The symptom reduction, however, you could obtain much more accurately from the parent and the teacher assessment because that is something the child does not always recognize.

Dr. Wilens: You also get a more thorough report of side effects from talking to children. Also, in adolescents, self-report may be more sensitive to medication effect than parental report.  

Q: How do you deal with the problem of children being misdiagnosed?

 

Dr. Rosen: The thoroughness of the assessment process is important. The key to diagnosis is not the physical exam; 80% to 85% of the time it is based on the history. The guidelines are helpful in that they demand, particularly from the American Academy of Pediatrics, that feedback be received from more than one site—not only from parents, but also from other caretakers in the preschool group. I also send the questionnaire to family daycare providers as well as teachers who might not have a bias. Getting feedback from caretakers who are not parents, teachers, and even community members is key. And most important is getting feedback from mental health providers.

Q: Some patients request continuation of ADHD?medications but do not seem to have ADHD. How can you determine whether they are taking a medication as an addiction, or as a habit continued from necessity earlier in life?

 

Dr. Wilens: There is little evidence that these medicines are abused in a stable manner. There are very few methylphenidate addicts whose drug of choice are stimulants, especially the extended-release preparations. Most of the time when people are coming for referral for the diagnosis of ADHD, they have at least some aspect of ADHD?or some type of cognitive impairment that they are indicating is getting better with treatment. But there simply is not a lot of data out there that suggest that a lot of people are becoming addicts on these medications. In fact, a number of studies have been done using this class of agents in cocaine addicts either with or without ADHD. These studies indicate that stimulants do not make the addiction worse. Stimulants do not increase the craving, increase cocaine use, or increase drug-seeking behavior in hard-core addicts who have these conditions. I would not debate that occasional abuse may be occurring once in a while, but I?think in a public health forum it is not a major concern.

Dr. Rosen: Ask the partner of the individual who wants the medication to fill out a Child Behavior Checklist or an Adult Behavioral Checklist form. Or ask the parents to fill them out based on their memory of that individual as a child. It may provide some information about the child’s original biological predisposition.

Q: How would you explain the decreased comorbidity among ADHD children observed in the Multimodal Treatment of Children with ADHD (MTA) study?

 

Dr. Wilens: It may be difficult to translate findings in carefully screened study patients to the realities of unselected clinical patients. In clinical practices, where we treat everyone who walks through the door, we do not see subtle amounts of anxiety, we see robust anxiety. Further evidence for the comorbid nature of ADHD is provided by studies showing that family members have higher-than-expected degrees of the comorbidity in question. Even with depression, for which the argument can be made that it results from ADHD, we can determine through familial risk factors that the depression is really independent of the ADHD. So we have externalizing or converging ways to determine if there is a true comorbid disorder. The identification of comorbidity in ADHD is very significant, because the patient may not achieve a good ADHD outcome if the physician does not address the comorbidity.

Dr. Swanson: The types of children seen in different settings will demonstrate a referral bias. A clinic that has extraordinary expertise in treating bipolar disorder or depression will get more of these cases. A pediatric department will not get as many patients with serious comorbid conditions as will a psychiatry specialty clinic. Therefore each group may have a different best approach to treatment. 

Dr. Wilens: Epidemiological data shows that there is substantial comorbidity among ADHD patients. While some suggest that there is a referral bias, data such as those presented by Busch and colleagues10 show that children who are referred to specialty clinics are very similar in terms of comorbidity to those who are referred to pediatric practices. The difference is that specialists have the ability to make these assessments and thus diagnose them more frequently.

Dr. Swanson: In the MTA study, we had a systematic way of evaluating children. And if you look at the number of children with serious comorbid conditions, the ones that stay and do not remit over time, it is not at the levels generally described in the clinic work done in ones own practice. 

Dr. Wilens: Basing the argument on study data qualifies it. The ratio of patients screened to subjects enrolled in clinical studies, such as the MTA, is ~10:1. One has to be very concerned when generalizing study data to a clinical population. Clinical practitioners, I believe, would say that they are seeing much more depression and other comorbidities than were reported in the MTA trial.

Dr. Rosen: The MTA study found a 50% to 60% improvement when?patients were treated with the right dose of a stimulant, which also improved their comorbidity. However, this high rate may be a reflection of the fact that patients with more serious affective disorders, such as those on antidepressants or antianxiety agents, were not included. In addition, there was a numerically significant improvement with behavioral therapy in children with comorbid oppositional defiant disorder and anxiety disorders not serious enough to be treated with medication.

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