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Attention Deficit Disorder

Attention-deficit hyperactivity disorder is the most common behavioral disorder diagnosed during childhood and adolescence, with 2.8% of all youths 5 to 18 in the United States receiving methylphenidate in 1999. The conventional cardinal symptoms of ADD include age-excessive inattentiveness, usually in association with overactivity and impulsivity. Newer data and recommendations now support that a distinct subgroup of patients have ADD without hyperactivity or impulsivity. ADD has been classically associated with hyperactivity, attention deficit disorder, atention deficit disorder, attention defacit disorder

Hyperactive-Impulsive Attention-Deficit

Disorder

Most children with ADD-H present during preschool and elementary school years with behavioral problems. Usually, parents bring the child to the office complaining of either their child's hyperactivity, aggressiveness, uncontrollable behavior, or refractoriness to ordinary parental discipline measures, including corporal punishments; or teacher complaints that the child is extremely disruptive, cannot sit still, jumps from the seat, is constantly distracted, can't keep the hands off of other children, or performs poorly in school, often because of perpetual overactivity.

The impulsivity of patients with ADD-H is manifested by failure to recognize social consequences of their behavior and outspokenness. These children often suffer from 

Inattentive Attention-Deficit Disorder

In contrast, patients with ADD-I usually present in middle or high school years, predominantly with academic problems. August and Garfinkel coined ADD-I as the "cognitive deficit" form of ADD as opposed to ADD-H, the "behavioral"-hyperactive form. The grades of patients with ADD-I are often described as poor or less than expected. They typically seem "lost in space," sluggish, and inordinately disorganized, with an inability to focus. These

Prognosis

Schachar and colleagues reported a worse prognosis and lower cognitive functioning among pervasively versus situationally hyperactive children. Early age of ADD onset is associated with higher cognitive deficits, poor reading skills, comorbidity at age 11 years, and worse outcome at age 15 years. Clinical course and outcomes are significantly worse in those with ADD-H comorbid with conduct disorders, aggression, or both. ADD-H with aggression is associated with social disadvantage, family conflict, parental sociopathy, and ultimate poorer 

TABLE 2 -- SPECIFIC MEDICATIONS FOR ATTENTION DEFICIT HYPERACTIVITY DISORDER
Medication Dose Duration Titration Advantages Disadvantages
Methylphenidate
(Ritalin)
5, 10, 20 mg
0.3 to 0.6 mg/kg/dose b.i.d. or t.i.d. 2 to 4 hours Pills can be cut in half, but difficult Most popular stimulant; least negative effects on appetite and mood. Not labelled as "speed" or diet pill. Some differences between brand-name and generic, too short-acting, requires multiple dosing. Worse peaks and troughs. Recent negative press. Not approved for children < 6 years of age.
Methylphenidate SR
(Ritalin SR)
0.5 to 0.7 mg/kg/dose q.d. or b.i.d. 2 to 6 hours
Erratic
None Lowest rate of AEs among long-acting formulations Erratic, unreliable pharmacokinetics, occasional differences between brand-name and generic.
Dextroamphetamine sustained release capsules
(Dexedrine Spansule)
5, 10, 15 mg
0.15 to 0.3 mg/kg/ dose q.d. or b.i.d. 5 to 7 hours Capsules can be split in half (2.5 mg increments). See text. May be sprinkled for children unable to swallow pills. Less abuse potential than tablets. Appetite suppression and moodiness somewhat more common than with methylphenidate; avoid vitamin C simultaneously. Administer prebreakfast. Higher abuse potential.
Dextroamphetamine tablets
(Dexedrine)
5 mg tablets
0.15 to 0.3 mg/kg/ dose b.i.d. 3 to 5 hours Easy to cut in half Longer duration than short-acting methylphenidate (Same as spansules). Requires more frequent administration. Common form of "speed" on the street. Higher abuse potential.
Mixture of amphetamine salts
(Adderall)
5, 10, 20, 30 mg
0.15 to 0.3 mg/kg/ dose q.d. or b.i.d. 5 to 7 hours Easy to cut in half (2.5 mg increments). Reliable long-acting preparation, easiest of all medications to titrate, approved for 3 years and older. No recent published clinical trials. Otherwise apparently similar to dextroamphetamine spansules. Higher abuse potential.
Pemoline
(Cylert)
18.75, 37.5, 75.0 mg tablets and 37.5 mg chewables
1-2 mg/kg/day qd (once a day) 12 to 24 hours
Longest acting of all
Easy. Half-doses may be administered. Effects may not be apparent for several weeks. Longest-acting preparation, usually single daily dose. No abuse potential. Not considered a potential "street" drug. Alternative for adolescents or for patients with frequent homework. Lower rates of efficacy compared with other stimulants. Requires informed consent before prescribing and frequent serologic monitoring of LFTs. Onset of action may be from 3 days to 3 weeks.
Clonidine
(Catapres)
Transdermal patches
[TTS (1, 2, or 3)]
Start with 0.05 mg or tid or qid oral form. Increase by 0.05 mg tid weekly. Try transdermal patches replaced every 3 to 5 days in stable patients. Pills 4 to 6 hours Patches 3 to 5 days Half-doses can be used for pills or patches. Weekly increased dosing usually necessary. Most helpful in children with aggression, extreme overactivity, or conduct disorders. Use concomitantly with psychostimulants. Preferred therapy for children with concomitant tic disorder. Significant or severe problems with sedation. Not effective for inattention. Brand-name may be preferred over generic. Not FDA approved for behavioral pharmacotherapy. Discontinue gradually to prevent rebound hypertension.
AEs, adverse effects; LFTs, liver function tests; TTS, transdermal therapeutic system.

Psychostimulants Are "Addictive."

The stimulants are not narcotics and, in standard doses, seem to have no addictive properties for these children, as demonstrated by

Psychostimulant Medications Are Dangerous.

The safety of these medications is briefly addressed at the visit, with a general comment about their extremely safe track record if used appropriately. Serious side effects are exceedingly rare with these medications, even with pemoline, and the only reported mortalities with psychostimulant monotherapy have been related to the use of

Psychostimulant Medication Stunts Growth.

Some degree of weight loss is nearly universal with use of psychostimulants, albeit usually mild and transient. Most long-term studies have demonstrated little or no effects on long-term height growth among children treated with psychostimulants compared with untreated controls. When decreased appetite and weight loss are discussed, many parents excessively worry about their children's potential weight loss (e.g., "But he's so skinny already") and other

MEDICATION EFFECTS AND DOSING

Over time, pediatricians encounter patients who fit the diagnosis of ADD but who have compensated and require no further treatment. Only children whose symptoms significantly interfere in at least one area of functioning-socially, academically, or behaviorally-warrant therapy. "Target symptoms" for amelioration are selected and explained to the

SELECTION OF MEDICATIONS BY AGE GROUP

Psychostimulants

Initial Therapy

Initial therapy in children diagnosed with uncomplicated ADD always consists of one the psychostimulants: methylphenidate, dextroamphetamine, or a combination of dextroamphetamine and levoamphetamine (Adderall). These medications are extremely safe and require no serologic or hematologic monitoring. Patients may respond better to one or the other of these psychostimulants, and patients who do not respond to the initial choice can be treated with either remaining alternative. Interestingly, parent-rating scales favored dextroamphetamine over methylphenidate, probably secondary to the longer half-life of dextroamphetamine so that effects were observed at home and school. Barkley reviewed 15 studies using dextroamphetamine and 14 using methylphenidate and 

Children 5 to 14 Years of Age

Although selecting with which medication to initiate therapy may be somewhat arbitrary, in children 5 to 14 years old, either Dextroamphetamine Spansules or Adderall (mixture of amphetamine salts) may be preferred because of the longer, smoother duration of effects, reduced likelihood of midday school dosing with its subsequent stigmatization and teasing by classmates, ease of titration, and relatively lower costs. According to Pelham, Dextroamphetamine Spansules may be the preferred medication for children with ADD-H. This medication demonstrated equivalent or

Compared with methylphenidate, sustained-release Dextroamphetamine Spansules (and possibly Adderall) is a significantly more reliable and effective long-acting form of amphetamines. Furthermore, sustained-release preparations are preferred by the children themselves and are less likely to be a factor in nonadherence. As shown in, the spansules and Adderall allow for easier titration in 2.5-mg (half-dose) increments. Adderall tablets may be cut in half. Pediatricians should consider demonstrating to the parents that the dextroamphetamine Spansules can be twisted into two halves, and, by using the small "top" half as a measuring device, the beads from the capsule can be

Children 3 to 4 Years of Age.

Stimulant therapy is often avoided in children aged 3 to 4 years because of lower efficacy; the increased rate of problematic AEs, especially moodiness, irritability, and appetite suppression; and because of the lack of availability of a liquid formulation. Only highly aggressive and pervasively, behaviorally disruptive or defiant children in this group warrant therapy. Because of its reduced rate of AEs, usually short-acting methylphenidate, which can be crushed, is

Adolescents.

Prescribing psychostimulants for the adolescent population creates a significant dilemma for pediatricians, who must now choose between the standard stimulants, which demonstrate no evidence of lethality when used appropriately and singly but that are associated with the potential for being abused in this population versus pemoline, which has been associated with an exceptionally rare potential for liver failure in about 1 case per 2 years in the United States since 1975 (M. Yousefi, personal communication, 1997) but which has virtually no

Adverse Effects and Management

All psychostimulants produce very similar AEs (see Table 4 (Table Not Available) ). The most common AE is appetite suppression and subsequent weight loss, which varies from 0.5 kg to 2.25 kg. This anorexigenic response abates after 1 to 6 months. It may be somewhat more pronounced in children treated with amphetamines (versus methylphenidate) and in those who are overweight pretherapy. Mild headaches and stomachaches occur in about one fourth of children and resolve over 1 or 2 weeks. Weekend "drug holidays" may precipitate recurrence of these symptoms every Monday. Although insomnia is frequently reported, when stimulants are used in low to standard

Drug Holidays.

In patients who seem to have school-related, situational ADD or children or adolescents with ADD-I or milder ADD-H, drug-free holidays on weekends, holidays, and summer vacations can be considered, but only if no significant behavioral, social, or family difficulties are noted. Medication-free days tend to eliminate some of the

Tics.

Less than 1% of children with ADD develop tics. Previously, stimulants were believed to be contraindicated in children with Tourette's syndrome; however, current literature suggests that tics are not caused by stimulants but

Nonresponders to Stimulants

If minimal or no response is obtained initially or after a trial of two or three medications, the physician should carefully evaluate for compliance problems (e.g., not swallowing the pills, inadequate doses, generic substitution, concomitant vitamin C, or pilfering of pills) or other problems. For patients with ADD-H who are nonresponders to psychostimulants, the dose may be increased to the maximum reasonable level (about 1.5- to 2-fold above the standard dose) of medication or until bothersome AEs are observed. Generally, for nonresponders, the dose of medication can be pushed until weight loss or dysphoria is observed. If this fails, at least three different

Antidepressants

In the past, tricyclic antidepressants, despite their tighter margin of safety, have been the mainstay of second-line alternative treatment for the 10% to 20% of patients unresponsive to any psychostimulants. Nonetheless, for ADD-H, methylphenidate is clearly superior to imipramine and desipramine. In one study, imipramine was not effective in nonresponders to methylphenidate. In contrast, nortriptyline improved attention span and reduced impulsiveness among psychostimulant nonresponders. Maximal benefits are primarily observed in 

Selective serotonin reuptake inhibitors, which include sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and others, may be preferred adjunctive therapy for depressed adolescents with ADD, even though they have not been 

Bupropion

Bupropion (Wellbutrin), an anxiolytic drug that blocks uptake of serotonin and norepinephrine, is occasionally being prescribed off-label for nonresponders. In one double-blind, clinical trial, bupropion was not as effective as 

Clonidine

Clonidine, an alpha2 -noradrenergic agonist, particularly benefits patients who are hyperaroused, extremely overactive, oppositionally defiant, or who have conduct disorder. Clonidine may be becoming the preferred second-line class for children with severe ADD-H who do not respond to stimulants. Clonidine may also be used in