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The choice of ADHD medication should be made based on the patient's condition, the prescriber's familiarity with the medications, the ease of administration, and cost. Stimulants should be used first-line in most ADHD patients, although studies in groups of patients have shown no clear advantage of using one stimulant over anoth-er.17

Nonstimulants Atomoxetine

Atomoxetine is approved in both children and adults. In clinical studies, atomoxetine has demonstrated superior efficacy over placebo and either equivalent or inferior efficacy when compared with a suboptimal immediate-release methylphenidate dose or

Concerta (18 to 54 mg given once daily), respectively Atomoxetine may be used as a second- or third-line medication for ADHD.

Atomoxetine selectively inhibits the reuptake of adrenergic neurotransmitters, principally norepinephrine.18-21 Atomoxetine is metabolized through the cytochrome P450 (CYP) 2D6 pathway. Concurrent use of certain antidepressants (i.e., fluoxetine, paroxetine) may inhibit this enzyme and necessitate slower dose titration of atomoxetine. Approximately 5% to 10% of the population are CYP2D6 poor metabolizers, and

atomoxetine half-life is increased significantly in this population. The recommended dosing for atomoxetine depends on the weight of the patient and is given daily in

either a single or two divided doses (Table 42-2). In poor metabolizers, atomoxet-

ine should be dosed once daily at 25% to 50% of the dose typically used in normal

metabolizers. The maximum therapeutic effect of atomoxetine may take up to 4 weeks to be seen, which is significantly longer than what is required with stimulants. Common side effects of atomoxetine are similar to those of stimulants: dyspepsia, nausea, vomiting, somnolence, and decreased appetite. Some studies have reported an increase in blood pressure and heart rate.19-2 There is evidence that atomoxetine can slow growth rate and cause weight loss; thus, height and weight should be monitored routinely in pediatric patients 9-21 (Table 42-3). Further, atomoxetine labeling includes strong warnings about severe hepatotoxicity and increased association with suicidal thinking.

Atomoxetine is similar to extended-acting stimulants in that it can be given once daily in many patients. It appears to lack any abuse potential and is not a controlled substance.25 One big disadvantage of atomoxetine is cost compared with other ADHD medications (Table 42-4).

Due to the high cost, lack of long-term efficacy data, and few comparison studies with stimulants, atomoxetine should be advocated only if the patient has failed or is intolerant to the standard stimulant therapy (Fig. 42-1).


Bupropion is a monocyclic antidepressant that weakly inhibits the reuptake of nore-pinephrine and dopamine. Bupropion is effective for relieving symptoms of ADHD in children but is not as effective as stimulants.26,27 Similar results have been shown in adults. Specific dosing recommendations are outlined in Table 42-2. Bupropion is well tolerated with minimal side effects (e.g., insomnia, headache, nausea, and tremor). Side effects typically disappear with continuation of therapy and are minimized with slow titration of dose. Bupropion can worsen tics and movement disorders. It is a rational choice in an ADHD patient with comorbid depression.26 However, seizures have been associated with bupropion doses greater than 6 mg/kg/day28 Seizures related to high doses can be minimized by reducing the dose or switching to a longer-acting formulation. Owing to the propensity of seizures with bupropion, its use is contraindicated in patients with seizure and eating disorders.

Tricyclic Antidepressants

The TCAs, such as imipramine, can alleviate symptoms of ADHD, but they are less effective than stimulants. Like bupropion, TCAs likely will improve symptoms associated with comorbid anxiety and depression. Although TCAs block the reuptake of serotonin, it is the blockade of norepinephrine that is felt to be responsible for their anti-ADHD effects. TCA use in ADHD has declined owing to case reports of sudden death and anticholinergic side effects6,10 (Table 42-3). If a TCA is prescribed for a child or an adolescent, desipramine should be avoided due to a higher case fatality

rate compared with other TCAs. Further, TCAs may lower seizure threshold and increase the risk of cardiotoxicity (e.g., arrhythmia). Patients starting on TCAs should have a baseline and routine ECGs.

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