ADHD - Atention deficiency and hiperactivity disorder

ADHD

Epidemiology

The Centers for Disease Control and Prevention

(2005) conducted the National Survey of Children’s

Health during January 2003Y2004, asking parents of

more than 100,000 children ages 4 to 17 years whether

their child had ever been diagnosed with ADHD or

received medication treatment (as opposed to currently

being treated). The rate of lifetime childhood diagnosis

of ADHD was 7.8%, whereas 4.3% (or only 55% of

those with ADHD) had ever been treated with

medication for the disorder

Although only

40% of 18- to 20-year-old Bgrown up^ ADHD

patients met the full criteria for ADHD

Comorbidities

Studies have shown that 54%Y84% of

children and adolescents with ADHD may meet criteria

for oppositional defiant disorder (ODD); a significant

portion of these patients will develop conduct disorder

Etiology

Specifically, a meta-analysis of

83 studies with more than 6,000 subjects showed that

patients with ADHD have impairments in the executive

functioning domains of response inhibition, vigilance,

working memory, and some measures of planning.

Faraone et al. (2005b) reviewed 20 independent

twin studies that estimated the heritability (the

amount of phenotypic variance of symptoms attributed

to genetic factors) to be 76%.

Faraone et al. (2005b) identified eight genes in which

the same variant was studied in three or more studies;

seven of which showed statistically significant evidence

of association with ADHD (the dopamine 4 and 5

receptors, the dopamine transporter, the enzyme

dopamine "-hydroxylase, the serotonin transporter

gene, the serotonin 1B receptor, and the synaptosomalassociated

protein 25 gene).

Screening

The clinician should perform a detailed interview with

the parent about each of the 18 ADHDsymptoms listed in

DSM-IV. For each symptom, the clinician should

determine whether it is present as well as its duration,

severity, and frequency

Children suffering a severe head injury may develop

symptoms of ADHD, usually of the inattentive

subtype. Hyperthyroidism,

which can be associated with hyperactivity and

agitation, rarely presents with ADHD symptoms

alone but with other signs and symptoms of excessive

thyroid hormone levels.

Academic impairment is commonly due to the ADHD

itself. However, if there is no clear evidence of an

improvement in academic performance in 1 to 2 months

despite improvement of the ADHD, then psychological

testing for learning disorders is indicated

Treatment

It is also clear that behavior therapy alone

can produce improvement in ADHD symptoms

relative to baseline symptoms or to wait-list controls

Jadad et al. (1999)

reviewed 78 studies of the treatment of ADHD; six of

these studies compared pharmacological and nonpharmacological

interventions. The reviewers reported that

studies consistently supported the superiority of

stimulant over the nondrug treatment. Twenty studies

compared combination therapy with a stimulant or

with psychosocial intervention, but no evidence of an

additive benefit of combination therapy was found.

In the MTA study, children with ADHD were

randomized to four groups: algorithmic medication

treatment alone, psychosocial treatment alone, a

combination of algorithmic medication management

and psychosocial treatment, and community treatment.

Algorithmic medication treatment consisted of

monthly appointments in which the dose of medication

was carefully titrated according to parent and teacher

rating scales. Children in all four treatment groups

showed reduced symptoms of ADHD at 14 months

relative to baseline. The two groups that received

algorithmic medication management showed a superior

outcome with regard to ADHD symptoms compared

with those that received intensive behavioral treatment

alone or community treatment (MTA Cooperative

Group, 1999a [rct]).

Behavior therapy may be

recommended as an initial treatment if the patient’s

ADHD symptoms are mild with minimal impairment,

the diagnosis of ADHD is uncertain, parents reject

medication treatment, or there is marked disagreement

about the diagnosis between parents or between parents

and teachers.

Treatment

The physician is free to choose any of the two

stimulant types (MPH or amphetamine) because

evidence suggests the two are equally efficacious in

the treatment of ADHD.

Single daily dosing is associated with greater

compliance for all types of medication, and long-acting

MPH may improve driving performance in adolescents

relative to short-acting MPH (Cox et al., 2004 [rct]).

Physicians may use long-acting forms as initial

treatment; there is no need to titrate to the appropriate

dose on short-acting forms and then Btransfer^ children

to a long-acting form. Short-acting stimulants are often

used as initial treatment in small children (<16>

weight), for whom there are no long-acting forms in a

sufficiently low dose.

On average, there is

a linear relationship between dose and clinical response:

that is, in any group of ADHD subjects, more subjects

will be classified as responders and there is a greater

reduction in symptoms at the higher doses of stimulant.

There is no evidence of a global Btherapeutic^ window

in ADHD patients. Each patient, however, has a unique

dose-response curve.

After selecting the starting dose, the physician may

titrate upward every 1 to 3 weeks until the maximum

dose for the stimulant is reached, symptoms of ADHD

remit, or side effects prevent further titration, whichever

occurs first

Eight of the nine studies supported the efficacy of MPH

in the treatment of preschoolers with ADHD at

milligram-per-kilogram doses that were comparable

with those used in school-age children

Of note, only 37 of 279 enrolled

parents thought that the behavior training resulted in

significant or satisfactory improvement

Results from the short-term, open-label, run-in and

double-blind, crossover studies do show that MPH is

effective in preschoolers with ADHD (Greenhill et al.,

2006a). The mean optimal dose of MPH was found to

be 0.7 T 0.4 mg/kg/day, which is lower than the mean

of 1.0 mg/kg/day found to be optimal in the MTA

study with school-age children

Atomoxetine is a noradrenergic reuptake inhibitor

that is superior to placebo in the treatment of ADHD in

children, adolescents, and adults

Michelson et al. (2002) showed that although

atomoxetine was superior to placebo at week 1 of the

trial, the greatest effects were observed at week 6,

suggesting the patient should be maintained at the full

therapeutic dose for at least several weeks to obtain the

drug’s full effect. At the end of the treatment period,

atomoxetine led to a significant reduction in ratings of

symptoms of both ADHD and anxiety relative to

placebo, showing the drug to be efficacious in the

treatment of both conditions.

in a meta-analysis of atomoxetine and stimulant studies,

the effect size for atomoxetine was 0.62 compared with

0.91 and 0.95 for immediate-release and long-acting

stimulants, respectively

Bupropion is a noradrenergic antidepressant

that showed modest efficacy in the treatment of

ADHD in one double-blind, placebo-controlled trial

(Conners et al., 1996 [rct]). It is contraindicated in

patients with a current seizure disorder. It can be given in

either immediate-release or long-acting form, but may

not come in pill sizes small enough for children who

weigh <25>

A

gradual titration is required and clinical consensus

suggests the !-agonists are more successful in treating

hyperactive/impulsive symptoms than inattention

symptoms, In recent years clinical consensus has led to the use of clonidine as adjunctive therapy to treat tics

or stimulant-induced insomnia rather than as a primary

treatment for ADHD.

For stimulant medications, the most common side

effects are appetite decrease, weight loss, insomnia, or

headache. Less common side effects of stimulants

include tics and emotional lability/irritability.

If the patient’s ADHD

symptoms respond adequately only to a stimulant

medication that induces tics, then combined pharmacotherapy

of the stimulant and an !-agonist (clonidine

or guanfacine) is recommended (Tourette’s Syndrome)

Controlled trials of stimulants do not support the

widespread belief that stimulant medications induce

aggression. Indeed, overall aggressive acts and antisocial

behavior decline when ADHD patients are treated with

stimulants

In 12 controlled trials involving

1,357 patients taking atomoxetine and 851

taking placebo, the average risk of suicidal thinking

was 4/1,000 in the atomoxetine-treated group versus

none in those taking placebo.

examined all of the available

data and concluded that stimulant treatment may be

associated with a reduction in expected height gain, at

least in the first 1 to 3 years of treatment