Safety Profile of Atomoxetine in the Treatment of Adolescents and Children with ADHD

Atomoxetine is a selective norepinephrine reuptake inhibitor that is being developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Atomoxetine will be the first nonstimulant medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of ADHD. Throughout the testing phases, more than 2000 children and adolescents have been exposed to atomoxetine in clinical trials, with both the number of exposures and the length of exposure time increasing. Serious adverse events have not been clearly associated with the drug, and there have been few discontinuations due to adverse events. The most common drug-related event reported in trials has been decreased appetite and an initial period of weight loss followed by an apparently normal rate of weight gain. These events tend to appear early in the course of treatment with atomoxetine and then decline. Atomoxetine has also been associated with mild increases in blood pressure and pulse that plateau during treatment and resolve upon discontinuation. There have been no effects seen on the QTinterval, and the cytochrome P450 2D6 metabolism of patients seems to have little effect on safety or tolerability of the drug. This article will review the data from completed and ongoing clinical trials available at the time the New Drug Application was submitted to the FDA. Described are serious adverse events, discontinuations, and treatment-emergent adverse events. Specifically, cardiac effects and effects on weight, height, and metabolism that are related to treatment of ADHD with atomoxetine in children and adolescents are discussed.