Synopsis: Atomoxetine (Strattera) is a new, nonstimulant medication approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adults. Unlike methylphenidate and dextroamphetamine, which act primarily by blocking the reuptake of dopamine, atomoxetine is a selective norepinephrine reuptake inhibitor. It does not appear to be habit forming and is not a controlled substance.
|Name||Starting dosage||Dose forms||Monthly cost|
|Atomoxetine||Children, 0.5 mg/kg||10 mg, 18 mg, 25 mg, 40 mg, 60 mg||$ 90 once daily|
|(Strattera)||Adults, 40 mg||$180 twice daily|
Safety: The most significant safety concerns for children are weight loss and slowing of growth. In one trial, 19.3 percent of the children receiving atomoxetine lost at least 3.5 percent of their body weight with the typical dosage and gained less height when compared with children receiving placebo.1 Atomoxetine also can increase pulse and blood pressure, and the manufacturer recommends that the drug be used with caution in patients with hypertension, tachycardia, cardiovascular disease, or cerebrovascular disease.1 Approximately one in 15 white patients will slowly metabolize atomoxetine and can be expected to have serum levels 5 to 10 times normal and an exaggerated response.1 High serum levels also can be expected in patients taking drugs that inhibit the CYP2D6 pathway, such as fluoxetine and paroxetine.1 Atomoxetine is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs) or who have taken an MAOI in the previous 14 days; and treatment with an MAOI should not be initiated within 14 days after discontinuing atomoxetine.1 Atomoxetine has not been studied in children younger than six years, and long-term safety beyond 10 weeks is unknown.1 Atomoxetine is pregnancy category C.1
Tolerability: The most commonly observed adverse effects in clinical trials, with an incidence at least twice that of placebo, are dyspepsia, nausea, vomiting, fatigue, decreased appetite, and mood swings.1 Adverse events are more likely to occur in patients who are poor metabolizers and those taking the once-daily dose.1 The actual incidence of adverse effects in typical practice may be higher because several trials used genotyping to identify patients who were poor metabolizers of atomoxetine and either excluded these patients from the trial or limited the dosage.2,3
Effectiveness: Atomoxetine is more effective than placebo for the treatment of ADHD in children and adults. In four randomized, double-blind, placebo-controlled trials of nine weeks or less, atomoxetine was statistically more effective than placebo in reducing the ADHD Rating Scale scores in children ages six to 18 years.2,4,5 Two unpublished randomized, double-blind, placebo-controlled trials of 10 weeks‘ duration found that atomoxetine was significantly more effective than placebo in adults using the Conners’ Adult ADHD Rating Scale Screening Version.1 Atomoxetine's long-term effectiveness and its effect on social and academic success have not been evaluated. A 10-week single open-label trial of patients randomized in a 4:1 ratio to atomoxetine or methylphenidate found no difference in patient outcomes, but the trial was limited by the small number of patients receiving methylphenidate; the failure to conceal allocation to groups; short follow-up; and the lack of blinding of patients, physicians, and those who assessed outcomes.3
Price: The monthly cost of a once-daily dose of atomoxetine is approximately $90, no matter what strength capsule is prescribed (10, 18, 25, 40, or 60 mg). Twice-daily dosing will double the cost. Comparable costs of long-acting methylphenidate and amphetamine salts are about $75 per month. Average wholesale costs are based on Red Book, Montvale, N.J.: Medical Economics Data, 2003.
Simplicity: Atomoxetine is not a controlled substance, and it does not require observance of the stringent prescribing rules necessary for Schedule II drugs, such as methyl-phenidate and dextroamphetamine. Dosing of atomoxetine, unfortunately, is not straightforward because of the potential for excessive dosing in patients who are slow metabolizers. Children should be started at a low dose of 0.5 mg per kg of weight. If tolerated, the dose can be increased after at least three days to a target daily dose of 1.2 to 1.4 mg per kg. This may be given once a day or in divided doses, and it must be approximated using capsules. No liquid formulation is available. Adult patients are started at a daily dose of 40 mg, which, if tolerated, can be increased to 80 mg after a minimum of three days. Atomoxetine can be taken with or without food.
Bottom line: Atomoxetine is more effective than placebo for treating symptoms of ADHD in children and adults, based on short-term studies. Given safety concerns (growth retardation, potential adverse effects in slow metabolizers) and its high cost, atomoxetine should be considered only as an alternative for patients who are intolerant or unresponsive to stimulant medications such as methylphenidate.