to the editor: In a STEPS review, Dr. Lynch¹ states: “Given safety concerns (growth retardation, potential adverse effects in slow metabolizers) and its high cost, atomoxetine (Strattera) should be considered only as an alternative for patients who are intolerant or unresponsive to stimulant medications.” However, in our opinion, these claims are not supported by the data.

Atomoxetine is the first and only non-controlled medication to be approved by the U.S. Food and Drug Administration (FDA) for the treatment of attention-deficit/hyperactivity disorder (ADHD). In the first year after its FDA approval, more than 1 million patients were treated with Strattera. In a randomized, double-blind, placebo-controlled study² to assess potential abuse in adult patients, Strattera was not associated with a pattern of response that suggested stimulant or euphoriant properties. Strattera does not have a black box warning regarding the potential for abuse, unlike other medications used to treat ADHD.³

After starting Strattera, some patients initially may lose a small amount of weight (approximately 1.1. lbs [0.5 kg]). But in patients treated for at least 18 months, weight gain resumes and appears to follow a normal pattern during longer-term treatment. Preliminary findings indicate that Strattera is unlikely to have marked effects on juvenile growth or final adult height.⁴ Existing stimulant treatments for ADHD have been shown to slow growth and weight gain in children. At this time, there have been no head-to-head studies to compare the impact of Strattera and stimulants on growth. There is no need to adjust the dosage of Strattera based on genotype or to perform genetic testing before beginning treatment.

The FDA has closely examined the extensive research data on Strattera and has judged it to be a safe and efficacious agent for the treatment of ADHD in children, adolescents, and adults. At this time, it is the only FDA-approved treatment for ADHD in adults. Based on the safety and efficacy profiles of Strattera, it should be considered a valuable agent in the initial and maintenance treatment of patients with ADHD.

editor’s note: Eli Lilly and Company manufactures Strattera.

in reply: As Drs. Gerber and Allen note, the STEPS review¹ of atomoxetine (Strattera) was published in 2003 and relied on data published almost two years ago.¹ All published trials available at the time that piece was written evaluated the efficacy and safety of atomoxetine for up to only 10 weeks. My concerns about the long-term safety of this important new drug for attention-deficit/hyperactivity disorder (ADHD) were based on data that were then available.

Drs. Gerbers and Allen provide new information that “in patients treated for at least 18 months, weight gain resumes and appears to follow a normal pattern.” They reference a meeting presentation,² which I could not find in abstract form or in a publication. However, several of the same authors recently have reported the results of a trial evaluating atomoxetine treatment for one year in children with ADHD.³ Weight percentile decreased from 52.3 to 48.4 in those receiving atomoxetine, while it increased in the placebo group from 53.1 to 58.5 (P < .001). Similarly, height percentile decreased from 56.1 to 53.4 in those receiving atomoxetine and increased in the placebo group from 59.9 to 60.6 (P < .001).

The latest revision of the package insert for Strattera states under the warnings section, “there are no long-term, placebo-controlled data to evaluate the effect of Strattera on growth,” and “patients requiring long-term therapy should be monitored and consideration should be given to interrupting therapy in patients who are not growing or gaining weight satisfactorily.”⁴ If new data are indeed available, I urge the authors to submit these data to the U.S. Food and Drug Administration (FDA) and publish the results in a peer-reviewed journal.

The authors state, “there is no need to adjust the dosage of Strattera based on genotype or to perform genetic testing before beginning treatment.” The FDA does state, “routine laboratory tests are not required.”⁴ However, once genotyping tests become more available and affordable to the general public, it seems worthwhile to identify patients who are at higher risk for adverse effects. Under precautions, the package insert states: “Poor metabolizers (PMs) of CYP2D6 have a 10-fold higher AUC [area under the curve] and 5-fold higher peak concentration to a given dose of Strattera compared with extensive metabolizers (EMs). Approximately 7 [percent] of a Caucasian population are PMs. Laboratory tests are available to identify CYP2D6 PMs. The blood levels in PMs are similar to those attained by taking strong inhibitors of CYP2D6. The higher blood levels in PMs lead to a higher rate of some adverse effects of Strattera.”⁴ It also states, “Dosage adjustment of Strattera may be necessary when coadministered with CYP2D6 inhibitors, e.g., paroxetine, fluoxetine, and quinidine.”⁴

The authors did not mention one new piece of information released by the FDA concerning the safety of atomoxetine. Since their letter was submitted, the package insert was updated in December 2004 with a bolded warning about the potential for severe liver injury and the recommendation that tests should be performed on the first symptom or sign of liver dysfunction.⁴