Attention-Deficit Hyperactivity Disorder (ADHD)

Kytja K. S. Voeller, MD

Disclosures

J Child Neurol. 2004;19(10):798-814. 

In This Article

Treatment of ADHD

This section focuses on some general principles of the treatment of the child with ADHD.

The treatment of ADHD involves the selection of an appropriate medication at an appropriate dose in combination with behavioral therapy. A number of different medications are now available for the treatment of ADHD, and the generic names and trade names are listed in Table 2 .

A specific discussion of the selection of a medication for a given child is beyond the scope of this article, but it is worth a brief review of the Multimodal Treatment Study of Children With ADHD (MTA), which was cosponsored in 1992 by the National Institute of Mental Health and the US Department of Education.[125]

This study provides a great deal of valuable information about the treatment of ADHD. It was conducted at six different sites in North America and involved 579 boys and girls who met the DSM-IV criteria for ADHD, combined type, and their families. The children were randomly assigned to four different treatment conditions: medication only, medication plus behavioral treatment, behavioral treatment only, and "community care" (ie, after the initial evaluation, families were provided with a report summarizing the assessment results and a list of mental health resources in their community and were then followed as part of the study). The medication management protocol (used for the medication only and the combined treatment groups) involved a sophisticated titration phase: the child was tried on a range of doses (including placebo) given at breakfast, at lunch, and in the afternoon during a 28-day titration period. Medication and placebo followed a random schedule, and both the parents and the clinicians were unaware of the dosage or whether the child was receiving placebo or active drug. Daily records of behavior and side effects were kept, and the optimal dose was selected after the records were reviewed blindly by experienced clinicians at a different site. Of the 289 subjects who entered this segment of the study, 256 completed it. After the optimal dose was determined, the children were seen at monthly visits, and the response to the treatment and side effects were monitored. No side effects were reported in 35.9%, mild side effects in 49.8%, moderate side effects in 11.4%, and severe side effects in 2.9%. In about half of those children who had severe side effects (depression, worrying, irritability), the side effects might have been unrelated to the medication. Interestingly, teachers reported more side effects when children were on placebo, suggesting a "negative halo" effect, and teachers saw fewer side effects with increased dosage. Parents proved to be more reliable monitors of side effects, and many of the side effects occurred as an "end of dose" phenomenon (ie, they were worse as the medication was wearing off). The most common parent-reported side effect involved decreased appetite, stomachaches, tearfulness, trouble sleeping, headache, and a dull or listless appearance. (Parenthetically, it should be noted that some of these "side effects" are present in children with ADHD even before medication is started and can often be remedied by an adjustment in timing and dose.)

Behavioral treatment administered to the combined medication and behavioral treatment group and the behavioral treatment only group involved parent training, child-focused treatment, and a school-based intervention organized and integrated within the school. The child-focused program was based on the summer treatment program developed by Pelham and Hoza and involved an 8-week program, 5 days per week and 9 hours per day, delivered in group-based recreational settings, with specific rewards, time-out, and social skills training, as well as individualized academic skills practice and reinforcement of appropriate classroom behavior.[126] The school-based treatment involved 10 to 16 sessions of biweekly teacher consultation and 12 weeks of part-time interventions, with a paraprofessional working with the child. A daily report card was filled out by the teacher and went home with the child, to be reinforced by the parents on a daily basis. In short, the behavioral treatment was well designed and intensive, to a much greater degree than would usually occur in a standard clinical or school setting.[125]

At the end of the 14-month period, the results indicated that the medication management alone and combined medication and behavioral treatment group showed a considerably more robust response than the behavioral treatment alone and community care groups. Combined treatment was superior to the behavioral treatment for internalizing problems, oppositional or aggressive symptoms, and reading achievement scores. Another interesting facet of the study was that the medication dose was adjusted upward during the 14 months of the study, but the rate of increase was less marked in the combined therapy group. The optimal dose for most children was in the range of 1 mg/kg/dose, which is somewhat higher than is often used.[127] When the children were re-evaluated at the end of 24 months, 68% in the combined group, 56% in the medical management group, 34% in the behavioral treatment group, and 25% in the community care group showed improvement.[128]

Thus, in summary, the results of the MTA study support the use of medication in the treatment of ADHD. The rate of side effects was quite low. The combination of medicine and behavioral management was associated with a better 2-year outcome than the medication group alone. In the long run, the difference (68% vs 56%) was relatively small but was significantly better compared with behavioral treatment alone and community care. The behavioral treatment was extremely intense and involved (1) parent training, (2) individual work with the child, (3) integration of the school into the behavior program, and (4) a daily report card completed by the teacher, which was then used by the parents to deliver consequences. This large, well-designed study strongly supports the use of medication integrated with a behavioral program.

Adequate behavioral therapy involves intensive and prolonged parent involvement and cooperation from the teacher.

With regard to the parents' role in the management of ADHD, there is little question that the optimal management of a child with ADHD requires an enormous time and energy commitment on the part of parents to maintain an extremely high degree of consistency and structure. The goal is to help the child become autonomous in self-regulation. The parent needs to learn to act as an "accessory frontal lobe," at the same time helping the child to develop increasing insight and competence in his or her own behavioral regulation. Depending on the child's age and the associated learning and behavior problems, as well as the environment, this might not be an easy or rapid process. Very young children with ADHD require close parental supervision, and children in elementary and middle school need continuous monitoring and support for school work. Adolescents, particularly those who have been recently diagnosed and treated, pose a special challenge. They have had a number of years to develop dysfunctional strategies and require close supervision and support and usually individual therapy. Although the child with ADHD does well when provided with structure and predictability, this can be something of an oxymoron in a busy household.

In the role of "accessory frontal lobe," the parent must learn to anticipate problems and develop a tactful approach to dealing with them. For example, helping a young child get organized for school in the morning is often stressful for many families. A standard complaint is that the child with ADHD dawdles while getting dressed and delays the family's departure. (The frustrated mother of one of my patients reported that her 10-year-old daughter seemed to be unable to get dressed and get downstairs in time to eat breakfast, whereas her 5-year-old daughter was able to do this autonomously and consistently.) Although medication often decreases the severity of the problem of getting ready for school, the parent needs to provide support until the medication has taken effect in the morning. This requires making sure that the child gets up early enough and receives medication and, then, if necessary, is monitored during the dressing process (this does not mean dressing the child but rather helping the child stay on track and complete the process on his or her own). This also means that the parent needs to be up early enough to manage this process. It is important to make sure that the child has organized the backpack for school the night before, again requiring close supervision. Bedtime is another problematic time. Given that many children with ADHD (on or off medication) have difficulty settling down to sleep, a lengthy and predictable bedtime routine often needs to be in place to help the child calm down. When both parents work and arrive home after 5 pm, this whole process requires split-second timing and teamwork to prepare dinner, wash the dishes, supervise homework, perform the backpack check, and get the child to bed on time. If a parent is busy or absent, it is important that whoever takes over knows what the routines and expectations are. Having a child with ADHD spend time in multiple environments (school, an after-school program, a baby-sitter's home, and, if the parents are divorced, different homes) can be extremely disorganizing. Even when there are several children in a household, maintaining routines and anticipatory management strategies requires considerable managerial skill.

Unfortunately, many households have difficulty in managing these routines. Because ADHD is such a strongly genetic condition, one or both parents can also have ADHD, which often makes it extremely difficult for parents to regulate their own behaviors enough to adhere to such routines, let alone provide the systematic support that the child requires. In a study that examined the parenting styles of parents who described themselves as inattentive and impulsive, fathers with this profile reported lax parenting both before and after parent training. Even after parent training, they tended to overreact. Mothers who described themselves as having moderate levels of inattention had the most negative parent-child interactions.[129]

Although parent training is often very helpful, there are occasions when the situation improves only after the parent's own attention problems are medically treated. One mother complained that her son was unable to keep track of his homework, forgot his assignments, and, on the rare occasions when he did complete them, often forgot to turn them in. This pattern had gone on through elementary school, so that the boy (then age 12 years) was not particularly motivated to change his modus operandi . To effectively deal with this problem, his mother needed to monitor him closely, keep in touch with the school on a daily basis, and make sure that positive rewards occurred when he completed his work. After several months, it was apparent that she could not do this in a consistent manner. She recognized that some of these difficulties were due to her own inattention and, once she was started on medication for her own ADHD symptoms, was able to provide the required structure much more effectively.

Treatment of ADHD is not the same as treating a learning disorder, and vice versa. Given the high degree of comorbidity between ADHD and learning disorders, a child should be carefully evaluated for a learning disorder, and treatment should be put in motion for remediating the learning disorder.

Making sure that the child gets enough to eat, gets enough sleep, and has sufficient exercise is a crucial part of the treatment. Although medication might help a sleepy child stay awake during school, chronic sleep deprivation is not conducive to learning. It takes creative parenting to make sure that the child gets enough sleep and remains on schedule over the weekends. Some children require 10 hours of sleep, and the logistics of getting the child to bed on time while completing the rest of the evening routine are formidable. Eating is another problem: some children on medication are simply not hungry at dinner and start foraging for food about the time they are expected to go to bed. Parents often view this as stubbornness or manipulation, but it usually works better for children to eat if they are hungry. Making sure that they have eaten breakfast and have a snack in the afternoon is also helpful because psychostimulant medication can suppress hunger, and they might not be aware that they need to eat.

Vigorous exercise on a daily basis is extremely helpful not only for the cardiovascular benefits but also because exercise helps increase arousal and enhances brain-derived neurotrophic factor, which facilitates memory and learning.[130] Providing the child with opportunities to move around after working on a project for a given length of time is helpful. However, many parents have difficulty finding time for their own exercise program, let alone developing one for their children.

Encourage self-awareness and autonomy. Helping children with ADHD understand themselves so that they can function effectively is important. Telling them that they are "hyper," "ADHD," or "disorganized" (particularly if this is communicated in moments of anger) is much less helpful than defining the dysfunctional behavior in very concrete terms ("You have trouble keeping track of your homework, so we will work out a system together that will make it easier."). One 40-year-old man who had asked to be evaluated after his son was diagnosed with ADHD pointed out that when he was growing up, he always had the sense that whatever he was doing was "never enough." It had been made clear to him that if he just "tried harder" and "did something different," he would perform better. However, he had no idea what "trying harder" and "doing something different" meant. This emphasizes the need to lay out a very clear and explicit program. When a child tells a parent or a teacher that he or she cannot do something "because of the ADHD," this should be treated as a serious problem and addressed immediately; the child usually employs this as a way of not carrying out an unpleasant task. The more a parent or teacher buys into the "I can't do it because I have ADHD" routine, the more the child will use this excuse.

A child's compliance with a routine should be closely monitored, and reminders as well as consequences should be provided. Children with ADHD cannot monitor their own behavior well, so frequent pleasant and focused reminders when they are drifting away from the program are helpful. Rewarding compliance with routines works better than punishing noncompliance, and sometimes letting a child experience a "natural consequence" helps reinforce the routine. Thus, if a child does not perform the nightly routine of checking the backpack and forgets homework, a series of natural consequences might ensue. (However, if the child's teacher does not respond with an immediate consequence if the homework is not turned in, the child learns that it is not very important to perform this routine.) Natural consequences are usually better than "unnatural" consequences. When it comes to long-range projects, parents need to be aware that it is extremely difficult for a child with ADHD to anticipate and plan a long-term project, so monitoring homework and providing tactful reminders and assistance ("Let's plan out how you're going to tackle your book report that is due next month"; "Have you put the report in your backpack?") are more helpful than allowing the due date to creep up or to let the child forget the final version. If a child has done well working on such a long-range project, but then forgets to turn it in on time, such a "natural consequence" might be unnecessarily harsh.

Teacher involvement is crucial. The teacher is a very important player in this situation. If there is minimal feedback from the teacher, or it does not occur in a very timely fashion (ie, the same day), it is almost impossible to improve the situation. A child learns quickly that if the homework assignment is written illegibly or is "forgotten," or if he tells his parents convincingly (but untruthfully) that he "has no homework," or the necessary workbooks or other materials are not brought home, then the homework cannot be completed. At 7 o'clock in the evening, it requires a herculean effort for the parent to correct the situation. This strongly reinforces homework avoidance. Children with ADHD benefit enormously from daily communication between the parent and teacher, with the focus on fixing responsibility on the child and teaching the child to monitor his or her own homework. However, this means that the teacher must check the homework list, might need to remind and monitor what materials the child is taking home, and provide immediate feedback to the parent if homework is either not turned in or is substandard. The parent then becomes responsible for delivering prompt rewards or negative consequences. Be forewarned: training these behaviors takes a long time and requires great persistence on the part of parents. I have worked with children who have perfected the art of "flying under the radar." One normally intelligent but language-disordered 12-year-old boy was able to generate such a cloud of confusion around homework that he almost never had to do it (his family had no idea of the status of his homework). When the parent and teachers began to communicate very closely and a tight behavioral program was set up, it required almost 24 months for this child to begin to change his behavior.

Parents and teachers sometimes state that a child cannot have ADHD because the child is not "hyper." Some believe that psychostimulant treatment is designed to "slow the child down, and find it hard to imagine that a child who is slow-moving, dreamy, chronically disorganized, and somewhat unaware of his or her surroundings would benefit from the same medication used to treat a child with rampant hyperactivity and impulsivity, but the medication works well in both situations. Psychostimulant medication appears to activate neural networks, subserving performance of specific tasks.[131]

A number of different types and formulations of medication are now on the market. Medications used to treat ADHD act by inhibiting the dopamine transporter (methylphenidate) or increasing dopamine release into the synaptic cleft (dextroamphetamine), or a combination of both mechanisms. Although the vast majority of children respond to methylphenidate or dextroamphetamine, an occasional child does not. Medications that increase norepinephrine (eg, tricyclic antidepressants) might be useful in treating children who have failed psychostimulant treatment.[132] Bupropion and atomoxetine (both of which increase central dopamine and norepinephrine) are also medications that might be helpful in this situation. Pemoline, which has the potential for liver damage and requires repeated blood tests, is useful in the treatment of drug-abusing adolescents. Modafinil, which is used to treat narcolepsy or daytime drowsiness in adults with partially treated sleep apnea, might also be helpful.

When the diagnosis of ADHD is made and medication is recommended, parents often state that ADHD is diagnosed too frequently, and the solution is to "throw medicine at it" rather than look for "the root cause." As discussed above, the root cause involves dysfunctional brain circuits, which are either genetic or acquired, and the most effective treatment involves psychostimulants and behavioral treatment.

What are the risks of not treating ADHD? Although parents are often concerned that starting a child on psychostimulant medication will increase the risk of drug abuse in later life, available data would suggest that it is quite the reverse. Children with ADHD, particularly those who are not treated with psychostimulants, are at much greater risk of drug abuse than children without ADHD.[133] They start smoking at an earlier age than peers, possibly because nicotine enhances attention.[134] They also tend to be drawn into deviant peer relationships, which are strongly associated with drug abuse, and are especially vulnerable to these undesirable social influences, further increasing the risk of drug abuse.[135] Appropriate treatment with psychostimulants has been shown to reduce the risk of later drug and alcohol abuse in children with ADHD.[136] Children with ADHD who are on stimulant therapy are three to four times less likely to abuse drugs than those who are untreated.[137] In fact, one study demonstrated that treatment with psychostimulants in high school appeared to protect against hallucinogen abuse by adulthood.[138]

Despite concerns regarding its addictive potential, methylphenidate is not a very good addictive medication unless it is administered intravenously. Methylphenidate binds to the dopamine transporter and increases dopamine levels in the brain. This is similar in its mechanism to cocaine, but the euphoric effects and addictive potential of cocaine occur because it is administered in ways that result in a very rapid increase in blood level, with about 60% of dopamine transporters blocked. In addition, cocaine remains bound to the dopamine transporter for very brief periods of time; therefore, repeated high intravenous doses have euphoric effects and set the stage for abuse. In contrast, methylphenidate remains bound to the dopamine transporter for several hours; therefore, repeated doses have very little effect.[139] When methylphenidate is administered by mouth at a standard clinical dose, euphoric effects are not present.[140] Dextroamphetamine has a somewhat more complicated mechanism of action. There are many medicines that, if administered incorrectly, are dangerous but at the appropriate dose are lifesaving (eg, insulin or digitalis).

Some parents worry that starting children on a psychostimulant medication will commit them to lifelong use. Although no parent wants to see his or her child on medication, particularly a chronic medication, there are some situations in which a child needs to take medication and continue it throughout life (eg, children with diabetes require insulin, children with endocrine disorders or asthma need to take medicine). ADHD is no different. It is a chronic, impairing disorder that is perhaps not as life-threatening as diabetes but is, nonetheless, impairing. The real issue is to weigh the risks of treatment against the risks of nontreatment.

What are the risks of nontreatment? Children with ADHD who are not treated are likely never to live up to their potential in school, are at greater risk of behavior disorders[141] and psychiatric disorders (major depression and personality disorders),[142] have a much higher rate of traffic violations than peers,[143] and, untreated, are more likely to abuse drugs than children with ADHD who are treated.[138]

The recent information regarding the genetic basis of ADHD opens up the possibility that more sophisticated pharmacologic management of this disorder will become possible. Although most patients respond well to psychostimulants, a small group has atypical responses or is at increased risk of undesirable side effects. Understanding the genetic basis of ADHD and how different drugs affect the central nervous system will make it possible to effectively select an appropriate medication. A few examples will suffice. Children with ADHD who are homozygous for the 10-repeat allele at the dopamine transporter 1 ( DAT1 ) gene show a poor response to methylphenidate.[144] A SPECT study of children with this genotype, who showed some response to methylphenidate, had significantly higher regional cerebral blood flows in the medial frontal and left basal ganglia regions than children who did not have this genotype.[145] Individuals with two catechol O -methyltransferase Met/Met alleles (resulting in slower elimination of dopamine from synapses) performed less well on tasks assessing prefrontal executive function when treated with dextroamphetamine, whereas performance on these tasks was enhanced by dextroamphetamine in subjects with a different (the Val/Val) phenotype.146 Because a number of different genes are involved in the ADHD phenotype, understanding these complex interactions will take much further investigation.


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