Atomoxetine (originally named tomoxetine), a new therapy for attention deficit hyperactivity disorder (ADHD) marketed by Eli Lilly, was compared to methylphenidate in a prospective, randomized, open-label study for 10 weeks duration, at the University of Nebraska Medical Center, Massachusetts General Hospital, Mount Sinai Medical Center, Carolinas Medical Center, and Lilly Research Laboratories. Boys aged 7 to 15 years and girls aged 7 to 9 who met DSM-IV criteria for ADHD were admitted to the study. Of 228 patients randomized, 184 received atomoxetine and 44 methylphenidate. Atomoxetine was titrated to a maximum of 1 or 2 mg/kg per day, in 2 divided doses AM and late afternoon. Methylphenidate was initiated at 5 mg one to three times daily, not to exceed 60 mg daily. Both drugs resulted in marked improvement in inattentive and hyperactive-impulsive symptoms, with no significant differences in effectiveness and toxicity. ADHD-IV Rating Scale total scores were as follows: atomoxetine baseline 39.4 [8.5], endpoint 20 [13.9]; and methylphenidate baseline 37.6 [9.7], endpoint 19.8 [16.6]. Adverse events requiring drug withdrawal occurred in 10 of 184 (5.4%) patients receiving amoxetine and 5/44 (11.4%) for methylphenidate (p=.175). Results of amoxetine treatment for ADHD are comparable to those of methylphenidate. 
COMMENT. Atomoxetine is an inhibitor of presynaptic norepinephrine transporter with minimal affinity for other noradrenergic receptors. Efficacy in children with ADHD has previously been demonstrated in 3 double-blind, placebo-controlled trials. The present study shows comparable efficacy to that of methylphenidate.
Atomoxetine is metabolized through the cytochrome P450 2D6 isoenzyme (CYP 2D6) pathway, with 2 phenotypes, one being rapid or extensive metabolizers (90% of the US population) and the other, slow or poor metabolizers (10% of population). CYP 2D6 genotype was determined at study entry to determine which patients should receive smaller doses and those who may require higher amounts. The final dose in poor metabolizers was one third that used in extensive metabolizers (0.5 mg/kg/d versus 1.5 mg/kg/d). Although the safety and tolerability of these doses appeared to be similar in the 2 groups, further studies will be needed to define safety in the poor metabolizers. Should determination of the genotype for slow metabolizers be necessary before starting treatment, this would seriously detract from the use of atomoxetine in practice.