Diagnosing and treating a child?s ADHD is often not enough. Most patients have coexisting developmental or psychiatric disorders that must be addressed.
Diagnosing and treating a child's ADHD is often not enough. Most patients have coexisting developmental or psychiatric disorders that must be addressed.
Although considerable attention recently has been given to the diagnosis and treatment of attention deficit hyperactivity disorder, parents and clinicians often focus on ADHD symptoms and fail to appreciate that most children with ADHD have one or more associated (comorbid) conditions. For the sake of accurate clinical assessment and effective treatment, these comorbidities cannot be ignored. Pediatricians must be aware of the various developmental and psychiatric disorders that often coexist in children and adolescents with ADHD.15
The prevalence of comorbidity in children with ADHD has been estimated to range from 9% to 50%, depending on the comorbidity (Figure). Various clinical factors, age, sex, and subtype of ADHD influence the prevalence of specific disorders. Conduct disorder, for example, is far more prevalent in adolescent boys with ADHD, combined type, than in grade school girls with ADHD, inattentive type.
Given the high risk of comorbidity in children with ADHD, the American Academy of Pediatrics (AAP) recommends that clinicians routinely and systematically screen for comorbidity as part of any evaluation for ADHD.6 It is not sufficient to rely on epidemiologic associations to limit clinical assessment to conditions that are statistically most probable. Remember, too, that several conditions in the differential diagnosis of ADHD, such as disorders of language and learning, often coexist with ADHD itself.
Clinical vigilance for comorbid conditions does not end with the comprehensive evaluation of the child with ADHD. Most comorbid developmental and psychiatric disorders typically are evident only after ADHD has been diagnosed. Although the incidence of Tourette syndrome is higher in children with ADHD than in others, for example, tics typically begin several years after ADHD symptoms initially appear. Similarly, most children with ADHD, combined type, manifest symptoms during the preschool years, yet associated learning disorders generally aren't evident until the early grade-school years. Other comorbid conditions, such as substance use disorder, are not likely to present until adolescencemany years after ADHD was diagnosed.
Assessing and monitoring for comorbid conditions is important because many of these conditions require specific additional interventions to minimize impairment, maximize function, and optimize outcome. Although treatment with behavioral therapy or medication may be sufficient to address impairments associated with ADHD, failure to consider and identify coexisting conditions will generally lead to a suboptimal treatment plan. Children with ADHD and comorbid conditions generally require a multimodal therapeutic approach.
In its recently released diagnostic guidelines, AAP emphasizes the importance of routinely screening for comorbidity as part of the ADHD evaluation.6 The ADHD Toolkit, a set of forms developed by AAP in conjunction with National Initiative for Child Healthcare Quality, includes questions that focus on common psychiatric comorbid conditionsconduct disorder, oppositional defiant disorder, anxiety disorder, and depression. The toolkit does not, however, include assessment instruments for developmental comorbidities.
Coordination problems, sleep disorders, Tourette syndrome, and enuresis and encopresis are common developmental comorbidities of ADHD (Table 1).
Developmental coordination disorder (dyspraxia)
Tics and Tourette syndrome
Enuresis and encopresis
Developmental coordination disorder (dyspraxia). Clinicians have long recognized the clinical association between hyperactivity and clumsiness in children. Yet discussions of comorbidity seldom include the clinical diagnosis of dyspraxia or "developmental coordination disorder," and the pediatric or psychoeducational evaluation of the child with suspected ADHD generally does not encompass a systematic assessment of motor coordination. Nonetheless, studies suggest that most children with ADHD have some deficits in motor coordination.
Pediatricians should inquire about motor skills for several reasons. Children with ADHD more frequently experience minor injuries than other children, perhaps because of clumsiness in addition to overactivity, poor impulse control, and a tendency to engage in risk-taking behavior.7,8 Lack of motor coordination can also lead to difficulties with team sports and free play. Deficits in athletic agility may result not only in increased risk of injury but will likely augment the risk of peer rejection and low self-esteem. One way to address the problem of a child with ADHD who has difficulty with competitive team sports (because of distractibility or dyspraxia), is to steer him, or her, toward swimming, tennis, karate, or track. These sports provide children with ADHD an opportunity to belong to an athletic team, yet they focus on the mastery of individual skill.
Asking parents a few specific questions about age-appropriate motor agility is probably sufficient to screen for motor difficulties. In the past, some observers suggested that the physical examination include an assessment for neuromaturational "soft signs," which were thought to support the ADHD diagnosis (for example, overflow movements such as pronation of the wrists when walking in eversion). Children with ADHD or dyspraxia may indeed have more soft signs than other children, but soft signs are neither sensitive nor specific as a diagnostic measure for ADHD. Similarly, although balance or coordination difficulties revealed by a neurologic examination may suggest dyspraxia, the more meaningful criterion is how the child functions in age-appropriate gross motor activities of daily living.
Learning disability. Although concordance rates vary widely, it is estimated that approximately one third of children with ADHD have a learning disability. The pediatrician therefore should assess any child with ADHD for a specific learning disability. Although educators may agree on the conceptual definition of learning disability, school districts vary considerably in how they define it operationally. As with ADHD, the definition of learning disability is qualitative and descriptive in nature; parents and professionals may therefore disagree about the presence or severity of a learning disability in a particular child.
Some clinicians prefer that a child have formal neuropsychological testing or a psychoeducational assessment before diagnosing ADHD. Although this multidisciplinary approach ensures that most associated learning disorders will not be missed, critics might counter that two thirds of these childrenthose who do not have a learning disabilityare being evaluated unnecessarily. Diagnosis of a learning disability does indeed require formal testing by a psychologist or special education personnel, but perhaps this testing should be triggered by the presence of any of several factors that should raise the clinician's index of suspicion (Table 2). I recommend deciding whether to evaluate a particular child with ADHD for a comorbid learning disability after reviewing his or her developmental history, family history, and academic performance.
Does the child:
Have a family history of dyslexia or another learning disability?
Have a preschool history of language delay?
Reverse letters or numbers after the age of 7?
Have difficulty with reading, writing, or math despite one-on-one adult supervision?
Continue to underachieve academically despite effective treatment of ADHD symptoms?
The child with ADHD is entitled to many of the same academic accommodations and special education interventions that the child with a learning disability receives under federal law. Indeed, a child with ADHD and a learning disability generally requires these accommodations and interventions in addition to pharmacotherapy or behavioral therapy, or both.
Tics and Tourette syndrome. Considerable controversy continues to surround management of tics in children with ADHD. Transient motor tics are common in young children and occasionally develop in the child with ADHD who is being treated with stimulant medication.9 The diagnosis of Tourette syndrome requires the presence (at some point) of at least two motor tics and one vocal tic during a one-year interval.10 To the extent that ADHD typically manifests before the age of 7 years and Tourette syndrome often presents after 7 years of age, many children with ADHD who develop motor and vocal tics are being treated with stimulant medication when their tics develop. Regrettably, the association between the appearance of tics and stimulant treatment of ADHD has led parents and professionals to infer causality. Although stimulants may exacerbate tics in a small percentage of patients, several well-designed studies have shown that most children with tics or Tourette syndrome can be safely treated with stimulants.11 Only a small percentage of patients with ADHD have tics or Tourette syndrome; on the other hand, at least half of patients with Tourette syndrome also have ADHD. (Patients with Tourette syndrome are also at increased risk of obsessive-compulsive disorder.)
In children with ADHD and tics, treatment should focus on whichever condition is most impairingusually, the ADHD. Recent studies suggest that children with ADHD and Tourette syndrome may respond better to the combination of a stimulant and an
2 agonist (for example, methylphenidate plus clonidine) than to either drug alone.12 Guanfacine is another
2 agonist that has been used in children with ADHD or Tourette syndrome, or both. Although not studied as extensively, some clinicians prefer guanfacine to clonidine because it has a longer half-life and may be less sedating. Atomoxetine, a recently approved nonstimulant medication for ADHD, may also be used in children with tics because it is not associated with tic onset or exacerbation. Information regarding atomoxetine's therapeutic profile in ADHD is still limited, however, and clinical experience suggests that it may have a smaller effect size and lower response rate than the stimulants. Results of a study assessing the efficacy of atomoxetine in children with ADHD and Tourette syndrome are expected shortly.
Mental retardation. Hyperactivity, poor impulse control, and distractibility are commonly seen in children with cognitive impairment. According to the diagnostic criteria for attention deficit disorder (ADD) that are provided in the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition (DSM-III), a candidate child's IQ must be higher than 50. (When DSM-III was published, the definition of ADHD was based on inattention, and DSM-III referred to the disorder we now know as ADHD as ADDwith or without hyperactivity.) Two subsequent editions (DSM-IIIR and the current DSM-IV) have eliminated the IQ criterion, however.10,13,14 They state simply that the child's ADHD symptoms must be significant compared with other children of the same developmental age.
Although most children with mental retardation are identified during their preschool years because of delayed language development, some children with mild mental retardation may first be recognized in the early grade school years after reports of academic difficulties, inattention, and behavior problems. Diagnosis of ADHD should be deferred in these late-presenting children until they are placed in a classroom setting more appropriate to their abilities (because academic difficulties, inattention, and behavior problems would be expected of a child in a classroom where the material is beyond his or her ability).
Sleep disorders are more common in children with ADHD than in other children.15 In fact, it has recently been suggested that sleep disturbances may cause ADHD symptoms in some children. Given that insomnia is also one of the more common side effects of stimulant therapy, pediatricians should carefully document a child's sleep history before starting any medication. Ask parents specifically about bedtime routines, snoring, and sleep disturbances.
If a child with ADHD has significant insomnia caused by stimulant therapy, try to adjust the medication dose and timing, counsel parents about the importance of sleep hygiene, and, if indicated, reassure them that the child is nevertheless getting adequate sleep. If these initial interventions prove insufficient, consider changing to another ADHD medication, such as atomoxetine, or try an herbal remedy (such as lavender oil or valerian),16 over-the-counter products (diphenhydramine, melatonin), or prescription medications (clonidine, trazodone, mirtazapine). The long-term safety of these sleep aids has not been proved. Although a few case reports exist of children who died when taking clonidine plus a stimulant, these cases are considered quite atypical because this combination of drugs has been used successfully in thousands of children.
Enuresis and encopresis. Toileting problems are also seen more commonly in children with ADHD than in those without the conditionagain suggesting the need for a good developmental history. Some young grade-school children with ADHD have occasional bowel or bladder accidents because they "waited too long" to use the bathroom. Rarely, stimulant therapy may exacerbate urinary incontinence. Because atomoxetine is associated with urinary retention in adults, it has been suggested that it might reduce urinary incontinence in children. A clinical trial of the drug reportedly is under way in children with enuresis.
Primary encopresis is atypical. Occasional daytime encopresis (especially "smearing") can result from waiting to the last minute to go to the bathroom. If a school-age child has repeated complete stool evacuations into his clothes, psychiatric evaluation probably is warranted. Whereas daytime soiling is likely behavioral or psychiatric in nature, nighttime soiling in school-age children is uncommon and suggests a neurologic basis.
Psychiatric disorders associated with ADHD include oppositional defiant disorder, conduct disorder, and, in older children, substance use disorder (Table 3).
Oppositional defiant disorder
Depression and dysthymia
Substance use disorder
Pervasive developmental disorder
Oppositional defiant disorder. Children and adolescents with ADHD (especially ADHD, combined type) are at increased risk of oppositional defiant disorder (ODD), which is characterized by a persistent pattern of "negativistic, hostile, and defiant behavior lasting at least six months."10 Suspect this diagnosis if the patient often loses his temper; frequently argues with adults; is easily annoyed by others; is often angry, touchy, or resentful; or commonly refuses to comply with adults' requests or rules or actively defies them. To the extent that oppositional behavior is typical of early childhood and adolescence, the clinician must be certain that the observed or reported behaviors are more frequent and have more serious consequences than typically noted in peers; in addition, these behaviors must result in clinically significant impairment in social or academic functioning. ODD behaviors are most commonly observed in the home and sometimes are not exhibited in a school or medical setting.
Prevalence figures for ODD vary considerably, depending on clinical factors and the assessment methods used. ODD is more prevalent in prepubertal boys than in girls, although the genderspecific rates are more comparable in adolescents. ODD typically presents during grade school or middle school, and a significant number of these patients later develop a conduct disorder. (Because most of the features of ODD are present in conduct disorder, ODD is not diagnosed if the patient also meets criteria for conduct disorder.)
Conduct disorder is characterized by a "repetitive and persistent pattern of behavior in which the basic rights of others or major age-appropriate societal norms or rules are violated."10 The two subtypes of conduct disorder are childhood-onset and adolescent-onset. Children with ADHD are most likely to develop childhood-onset conduct disorder. Of the various psychiatric comorbidities of ADHD, conduct disorder has the worst psychosocial prognosis.
As with ODD, conduct disorder is most common in boys with ADHD, combined type, although it typically is diagnosed a few years later than ODD is. Youth with conduct disorder are more likely than their peers to be sexually active at a young age, smoke, drink, use illegal substances, and engage in other risky behaviors. They are at markedly increased risk of academic suspension or expulsion, social ostracism, physical injury from accidents or fighting, and legal problems. As adults, people with ADHD and comorbid childhood-onset conduct disorder are at increased risk of persistent conduct disorder or antisocial personal disorder.
Anxiety disorders. Years ago, it was believed that children with "externalizing disorders" (ADHD, ODD, conduct disorder) did not also have "internalizing disorders" (depression, anxiety disorders). It is now clearly recognized that a significant number of children with ADHD do have a comorbid anxiety disorder. In the Multimodal Treatment Study of Children with ADHD (MTA) studya large, NIH-sponsored multicenter study in which different treatment approaches for children with ADHD were comparedabout 39% of the 579 children between 7 and 9.9 years with ADHD, combined type, met criteria for an anxiety disorder based on the parent's report.17
Although showing marked anxiety is a contraindication to treatment with stimulants, these children in the MTA study did indeed benefit from stimulant therapy. This subgroup also benefited significantly from the addition of psychosocial intervention, suggesting that a multimodal approach is most appropriate for patients with ADHD and anxiety disorders.17
Depression and dysthymia. Children and adolescents with ADHD often have low self-esteem because of their academic, behavioral, and social deficits. Although low self-esteem is often not evident when the young grade-school child initially is evaluated, it frequently becomes more of a worry as the years pass and schoolwork becomes more difficult, sports activities are more structured and competitive, and peers become increasingly selective and judgmental. Because low self-esteem is so common in older children and adolescents with ADHD, pediatricians must remain vigilant for itthrough parent interview, rating scales, and direct assessment of the child.
Although successful treatment of ADHD often minimizes problems with self-esteem, the positive effects of treatment on self-image may be moderated if a child also has a learning disorder or disability, which can further compromise academic functioning and peer acceptance. Although the special education services and classroom accommodations for which many children with ADHD are eligible can help students fulfill their academic potential, these same services and interventions can themselves be stigmatizing in some school and social settings. The child may feel that he is in a class with "dummies," or other students may tease him about his class placement.
Not surprisingly, some children with ADHD feel depressed, which further impairs functioning. Major depressive disorders in children often are not accompanied by vegetative signs, such as poor appetite and difficulty sleeping. (And, to complicate matters, these two symptoms of depression could instead be related to stimulant therapy.) To sort this out, parents and clinicians should determine to what extent the child is able to enjoy nonacademic activities. The child with ADHD and low self-esteem (but not depression) may feel poorly about school, but she should be able to enjoy leisure activities and social relationships.
If parents, school personnel, or others are concerned about possible depression, immediate assessment is warranted. In addition to interviewing the parents, consider using one of several available rating scales. Immediate psychological or psychiatric evaluation is in order if anyone close to the child fears she might injure herself or others. If depression is diagnosed, assess the adequacy of the ADHD therapy. Children with significant depression require psychotherapy or treatment with medication. Selective serotonin reuptake inhibitors (SSRIs) have been the most widely used antidepressant medication in recent years. Concerns have been raised about increased suicide risk with SSRI treatment, however. The FDA is reviewing these data. Other possibilities are bupropion and the tricyclic antidepressants. Anecdotal reports suggest that atomoxetine may be helpful as well.
Be alert for possible drug interactions if two or more medications are being prescribed to address ADHD and depression. Atomoxetine must be dosed more cautiously in patients on certain SSRIs, for example, because metabolism of atomoxetine is delayed in the presence of paroxetine or fluoxetine. Desipramine and stimulants have been associated with a few cases of sudden death in young people; nortriptyline has been used safely with stimulants. The American Heart Associationbut not AAPrecommends cardiac monitoring for patients being treated with the combination of a stimulant and a tricyclic antidepressant.
Bipolar disorder is one of the more recently recognized and poorly understood of the psychiatric ADHD comorbidities. The validity of the DSM-IV diagnostic criteria for this condition in children has stirred considerable controversy and confusion.18,19 Many children with ADHD are later diagnosed with bipolar disorder, although it is unclear whether the ADHD was a misdiagnosis or a comorbid condition, or developed into bipolar disorder. Suspect bipolar disorder in the child with ADHD who shows significant mood lability or irritability, especially if it is exacerbated by stimulant treatment. Bipolar disorder in a parent or another close relative is also a risk factor for this condition. Patients with suspected bipolar disorder should be referred, ideally to a child and adolescent psychiatrist, for assessment and management.
Substance use disorder. An ADHD diagnosis increases the risk of later substance use disorder. Studies show that young people with ADHD are not only more likely than their peers to develop substance use disorder but to do so at an earlier age. Although some parents and professionals attribute this finding to the use of stimulant therapydecrying methylphenidate as a "gateway drug"the data strongly refute this widespread misperception.20,21 Effective treatment with stimulant medication actually reducesstrikingly sothe likelihood of later substance use disorder. And because stimulant therapy repeatedly has been shown to be the single most effective treatment for ADHD, pediatricians must carefully explain the likely benefits and side effects of pharmacotherapy so that families do not forgo this treatment option for the wrong reason. Also be alert to the possibility that teenage patients may abuse and divert stimulant medicationalthough the new, longer-acting, once-a-day medications reduce this risk.
Pervasive developmental disorder. According to the DSM-IV, children with a severe and pervasive impairment in communication or reciprocal social interaction or who demonstrate stereotyped behaviors, interests, or activities have pervasive developmental disorder (PDD). This umbrella term includes autistic disorder, Asperger disorder, and PDD-not otherwise specified (NOS). Many academicians and cliniciansincluding meprefer autism spectrum disorder (ASD) as an alternate umbrella term for PDD. Because most ASDs are identified during the toddler or preschool years, development of an ASD after a child is diagnosed with ADHD need not be a concern. The major exception to this rule is Asperger syndrome; in this form of high-functioning autism, the child does not have significant delays in early language development, and the diagnosis often is not made until grade school.
DMS-IV criteria stipulate that ADHD symptoms (hyperactivity, impulsivity, and inattention) "do not occur exclusively during the course of a PDD." Nonetheless, many clinicians diagnose ADHD in children with an ASD. This is reasonable in children with Asperger disorder or very mild PDD-NOS. On the other hand, parents of a child with "classic" autism who is also hyperactive, impulsive, and inattentive are ill-served by an additional diagnosis of ADHD. For these patients, the World Health Organization's diagnosis of "hyperkinesis with developmental delay" is more appropriate.
Assessing ADHD symptoms in children with an ASD can be difficult because many of these children also have cognitive delays; their behavior therefore must be compared with that of children of the same mental age. Furthermore, norms for ADHD-focused rating scales do not necessarily apply to children with ASD. In these children, ADHD rating scales should be interpreted with caution because the scores are based on ratings of "neurotypical" children in mainstream educational settings.
Even if a child has a diagnosis of ASD, behavioral or pharmaceutical treatments should be implemented to address ADHD symptoms that significantly impair function. In the past, observers proposed not using stimulants in patients with autism because the stimulants were thought to be ineffective or to exacerbate symptoms. In fact, many children with autism and other ASDs will benefit from stimulant therapyalthough the response rate may be somewhat lower than in other patients. Depending on clinical response as well as symptom range and severity, other medications may be needed for treating hyperactivity in the child with an ASD. Consider an
2 agonist (clonidine, guanfacine), an atypical neuroleptic (such as risperidone), atomoxetine, or naltrexone. The child with an ASD also may benefit from treatment with an SSRI if she has obsessive-compulsive behaviors that interfere with function. Pharmacotherapeutic intervention is also sometimes necessary for aggression or a seizure disorder, both of which are more common in children with these disorders.
The AAP's diagnostic guidelines emphasize the importance of evaluating developmental and psychiatric comorbidity as part of the initial assessment of any child with suspected ADHD.6 AAP treatment guidelines likewise highlight the need to assess comorbidity whenever children with ADHD fail to respond adequately to treatment.22 Remember that most children with ADHD have one or more comorbid conditions. To increase the chance of an optimal clinical outcome, these associated disorders should be promptly identified and treated effectively.
Although pediatricians cannot be expected to diagnose and treat all ADHD-associated conditions, they often can play a critical role in doing so. Psychologists, special educators, physical therapists, occupational therapists, and speech-language pathologists may also be helpful in assessing some comorbid conditions. The decision to turn to a consultant probably will depend not only on the specific clinical features of the child but on the professional expertise of the pediatrician and available resources in the community.
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21. Barkley RA, Fischer M, Smallish L, et al: Does the treatment of attention-deficit/hyperactivity disorder with stimulants contribute to drug use/abuse? A 13-year prospective study. Pediatrics 2003;111:97
22. American Academy of Pediatrics. Subcommittee on Attention-Deficit/Hyperactivity Disorder and Committee on Quality Improvement: Clinical practice guideline: Treatment of the school-aged child with attention-deficit/hyperactivity disorder. Pediatrics 2001;108: 1033
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