COMMENTARY

Attention Deficit/Hyperactivity Disorder: A Common Diagnosis?

Laurence Greenhill, MD, Tami Benton, MD, Syed Imran Tirmizi, MD

Disclosures

February 04, 2003

Introduction

Attention deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders of childhood and adolescence as well as the most common disorder among children and adolescents referred for mental health services.[1,2,3] ADHD is characterized by developmentally inappropriate overactivity, distractibility, inattention, and impulsive behavior. It affects 3% to 8% of children and is associated with cognitive, social, and academic impairments.[4] The impairments in executive functions, attention, impulse control, and activity modulation cause secondary impairments in organization tasks, academics, and decision making that may occur in academic or social environments.

Recent research indicates that ADHD may persist into adulthood in 10% to 60% of childhood onset cases,[5,6,7,8] suggesting that adult ADHD may be a relatively common but underidentified disorder. It also may be overlooked when it occurs as a comorbid diagnosis.[9]

This syndrome has been known for more than 40 years as hyperkinetic reaction, minimal brain dysfunction, and other names.[10] Since the observation nearly 60 years ago that dl-amphetamine reduced the disruptive symptoms of hyperkinetic children, psychostimulants have been used to treat ADHD.[11,12] Between1990 and 1993, ADHD-related visits to primary practitioners increased from 1.6 to 4.2 million per year.[13] Ninety percent of those children were treated with medications, 71% with the stimulant methylphenidate. More than 10 million prescriptions were written for methylphenidate in 1996.[14]

The prevalence estimates of ADHD range from 1.9% to 17.8%[2,3] and vary by method of ascertainment, diagnostic system, measures used, informants, and the population sampled. Current Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) prevalence estimates in children are closer to 10%.[15] In children of elementary school age, the ratio of boys to girls ranges from 3:1 to 9:1 in clinical settings and 2:1 in community surveys.[16] Teachers identified fewer girls than boys with ADHD symptoms, but girls are thought to constitute 10% to 25% of those with ADHD. The male to female ratio ranges from 4:1 for the predominantly hyperactive impulsive type to 2:1 for the predominantly inattentive type.[15] Among older adolescents, the ratio is 1:1.[17]

Research has improved our understanding of the pathophysiology of ADHD. Positron emission tomography (PET) scanning has demonstrated that adults with past and current histories of ADHD showed 8.1% lower levels of cerebral glucose metabolism than controls,[18] with the greatest differences in the superior prefrontal cortex and the premotor areas. The potential impact on executive functions could affect one's ability to plan, organize, pay attention to details and instructions, screen out irrelevant information, carry out a plan through to completion, and avoid distractions.[19,20] Other studies support the involvement of the dopaminergic and noradrenergic systems in ADHD.[21,22]

Twin and family studies show high habitability of ADHD. Several studies have replicated an association between a specific allele for the dopamine 4 receptor subtype (DRD4 allele) with childhood ADHD.[23,24,25]

Other potential etiologic factors for ADHD include low birth weight, birth trauma, traumatic brain injury, fetal alcohol syndrome, heavy metal poisoning, deficiencies of minerals and vitamins, food allergies, traumatic brain injury, and prenatal nicotine exposure.[26,27]

The DSM-IV criteria for ADHD require that 6 (or more) of the symptoms of inattention OR 6 (or more) of the symptoms of hyperactivity-impulsivity occur often. These symptoms must have persisted for at least 6 months to a degree that is maladaptive and inconsistent with the child's developmental level. The diagnostic criteria also require that the hyperactive-impulsive or inattentive symptoms cause impairments in 2 or more settings (eg, at school [or work] and at home) and be present before the age of 7 years. ADHD is coded as combined type, predominantly inattentive type, or predominantly hyperactive-impulsive type.[28]

When diagnosing ADHD, a careful clinical assessment needs to determine if the symptoms and impairments observed might not be better explained by a diagnosis of bipolar disorder, anxiety disorder, major depressive episode, pervasive developmental disorder, psychosis, certain medical disorders (eg, thyroid dysfunction, nutrient deficiency states), or neurologic disorders.

Children with ADHD suffer impairments across multiple settings. School problems may include lower than expected grades, poor organizational and study skills, difficulty taking tests, and difficulty completing homework assignments.[29] Many patients, by the time they reach adolescence and late adulthood, display an established pattern of academic, familial, and social dysfunction.[30] Adolescents with ADHD are up to 3 times as likely as normal controls to have failed 1 or more grades, been suspended, or been expelled in the course of their academic careers.[31]

A total of 25% to 40% of adolescents and adults display delinquent behaviors or antisocial personalities at follow-up, particularly male patients who exhibited conduct problems at an early age.[6,7,32] They are more likely to be involved in auto accidents, traffic violations, and use tobacco or experiment with illicit drugs.[7,32,33] Children with ADHD are at increased risk for substance abuse as adolescents if they also had conduct disorder in childhood. Although disruptive behaviors are usually the reason for referral for treatment, ADHD is often associated with other psychopathologies and impairments.[34] The impulsivity and hyperactivity coupled with inattentiveness to social cues lead to impairments in social skills and peer relationships.[35,36] Severely affected children with limited behavioral control can cause impairments in the parent-child relationship.

Psychostimulants are the agents of choice for the rapid and effective treatment of hyperactive and impulsive behavior in children with ADHD.[37,38] There has been some controversy concerning the development of tolerance for stimulant effects on symptoms of ADHD or of a need to increase the dose to get the same response.[39]

At the optimal dose for a particular child, stimulants decrease fidgeting and finger tapping and increase on-task behavior in the classroom.[40] At home, stimulants improve interactions, on-task behaviors, and compliance. In social settings, stimulants improve peer nomination rankings of social standing and increase attention while playing sports.[41]

Stimulant medications available for clinical use are methylphenidate (MPH), dextroamphetamine (DEX), mixed salt amphetamine (AMP), and pemoline (PEM). Pemoline has been generally considered as a third-line treatment due to a rare side effect of liver failure. This stimulant is used as a last resort after a patient has failed a trial on 2 other stimulants and atomoxetine, , and only after a child's parents have filled out the consent form now included in the package insert.[42,43]

Short-term stimulant trials report robust efficacy of MPH, DEX, and PEM. More than 160 controlled studies involving more than 5000 school aged children demonstrated a 70% response rate when a single stimulant is tried.[44,45] Nearly 90% of patients will respond to both stimulants (MPH or DEX).[46]

The pharmacologic effects on behavior of the immediate-release formulations of MPH and DEX appear within 30 minutes, peak within 1-3 hours, and are gone by 4-6 hours.[47,48] Treatment should start with low doses of MPH, DEX, or AMP, usually starting with 5 mg of MPH or 2.5 mg of AMP/DEX; MPH is given after breakfast and lunch, with a third dose after school to help with homework and social activities. If there is no improvement in symptoms, the dose may be increased the following week. Behavioral rating scales should be obtained from teachers and parents to assist with assessment of response. The clinician may stop the upward dose titration when the symptoms have resolved or the patient develops side effects. Total daily MPH doses may be increased to up to 60 mg daily.[43,49,50]

Newer treatments for ADHD use once-daily dosing with long-duration stimulants.[51] The time response characteristics of standard stimulants are such that the plasma level troughs occur at the most unstructured times of the day, such as lunchtime, recess, or during the bus ride home from school. Some children, especially adolescents, avoid cooperating with in-school dosing because of fear of ridicule and the wish for privacy. Sustained-release stimulants avoid school-time doses.

The first extended-release preparations of methylphenidate included MPH-SR20 and Dexedrine Spansules. Within the past 5 years, osmotic delivery system (OROS) methylphenidate has been approved, which provides smooth release of methylphenidate and eliminates peak-trough effects. An external coating releases 22% of the medication immediately, and then an osmotic push compartment in the closed end of the 3-compartment capsule acts like a piston and pushes the remainder of the drug out of the laser-drilled hole at the other end, resulting in efficacy through 12 hours. It comes in 18-mg, 27-mg, 36-mg, and 54-mg tablets, providing dosing flexibility. The 18-mg strength of OROS-MPH delivers the same blood levels as 5 mg 3 times a day of immediate release.[43] Other long-duration preparations include the beaded methylphenidates (Metadate CD and Ritalin-LA).

Nonstimulant treatments also are available for the treatment of ADHD. Atomoxetine, with 4 double-blind controlled trials of more than 1000 children with ADHD, provides treatment for the cardinal symptoms of ADHD, and its sedating side effect makes it a suitable medication for the child who does not tolerate stimulants and has a sleep disorder. Bupropion has been shown in one double-blind, controlled study to have efficacy in the classroom in reducing ADHD behaviors in children.

Side effects of stimulants include appetite loss -- which can be minimized by giving breakfast immediately after or before morning doses of medication or adding high calorie drinks or snacks--and delay in sleep onset, which can be improved with alterations in dosing schedules, preparations, and sleep hygiene. In addition, gastrointestinal upset, weight loss, and tics may occur. More infrequently, children on stimulants may become socially withdrawn, pick at their skin, or become depressed. Side effects require further evaluation and medication adjustment.

Contraindications to stimulant treatment include psychosis, glaucoma, liver damage or abnormal liver function tests, drug dependence, and current use of monoamine oxidase inhibitors. Contraindications not supported by randomized controlled trials include motor tics, depression, anxiety, and seizure disorders.[43]

In addition to psychostimulants, behavioral treatments are recommended. These treatment options include behavior modification, parent training, teacher consultation, and social skill training. Counseling, family therapy, and supportive groups are helpful.[52]

Much has been done to improve our ability to effectively intervene in ADHD and to improve the quality of life for those affected by this disorder.

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