Effect of atomoxetine on Tanner stage sexual development in children and adolescents with attention deficit/hyperactivity disorder: 18-month results from a double-blind, placebo-controlled trial

To determine the effects of long-term atomoxetine treatment on sexual development in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) as compared with placebo and with a national US survey in non-Hispanic white children and adolescents. This double-blind, placebo-controlled, relapse prevention, multicenter trial was conducted in pediatric patients (6-15 years) with DSM-IV diagnosed ADHD and lasting for similar to 18 months. All patients received 10 weeks of open-label atomoxetine treatment (0.5-1.8 mg/kg/day). Patients responding in the last 2 weeks of treatment were randomized to double-blind treatment with either placebo or atomoxetine for up to 9 months, after which atomoxetine patients were re-randomized to either continued atomoxetine treatment or to placebo for up to another 6 months. Patients randomized to placebo at first randomization remained on placebo. The Tanner stage was assessed by the investigator at baseline and at approximately 6, 12, and 18 months, and the rate of sexual development (change in the Tanner stage) was compared between treatment groups. No statistically significant differences were observed between treatment groups either in sexual development (mean time, in days, to the first Tanner stage change: atomoxetine, 464.3 +/- 23.0; placebo, 433.1 +/- 14.4; p == 0.33) or in the duration of treatment exposure (atomoxetine, 315.3 days; placebo, 315.1 days; p == 0.90). Similar proportions of patients had at least one Tanner stage increase (atomoxetine: 27.1%%; placebo: 31.9%%; p == 0.39). Proportions of patients in each baseline Tanner stage group moving to higher stages were not statistically significantly different (p == 0.88, p == 0.18, p > 0.99, p == 0.68 for baseline Tanner stages 1-4, respectively). The puberty onset age was similar across treatment groups and consistent with US normative data. Long-term atomoxetine treatment was not associated with any appreciable impact on or delay in sexual maturation in children with ADHD compared with US normative data. Study limitations include the relatively short duration of exposure to atomoxetine treatment, and the fact that half of the patients had been previously treated with stimulants. In addition, the Tanner stage data were collected as a secondary measure. Trial was completed prior to the requirement to post trials at initiation and therefore does not have a registration number.