Pharmacotherapy of attention-deficit/hyperactivity disorder: nonstimulant medication approaches

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common chronic health conditions and mental disorders affecting school-aged children. Prevalence with a conservative estimate is reported to be 3-5% of this population. Boys are approximately three-times more likely to be diagnosed than girls. The diagnosis refers to a family of related chronic neurobiological disorders that interfere with an individual's capacity to regulate activity level, inhibit behavior and attend to tasks in developmentally appropriate ways. Signs and symptoms of ADHD are typically present during the preschool period or in the early elementary school years, and the diagnosis requires that difficulties were present at or before age 7 years and create problems or impairment in at least two areas of the child's life (e.g., at school, on the playground, on the bus, at home or socially with peers). Stimulants are the first-line medication in the psychopharmacological treatment of ADHD. Between 10 and 30% of those affected with ADHD may not respond to stimulants or may not be able to tolerate associated side effects, such as appetite suppression, sleep disturbance, mood difficulties or exacerbation of comorbid tic disorders. In such instances, or when families are unwilling to consider a stimulant, nonstimulant medications may be appealing. Several nonstimulant medications that affect noradrenergic and/or dopaminergic pathways have demonstrated efficacy in the treatment of ADHD, although effect sizes are comparable with methylphenidate, fewer data have accumulated regarding the safety profile of nonstimulants in general. This review focuses on etiology, assessment and treatment of ADHD, in particular alternative treatment approaches with various nonstimulant agents, especially atomoxetine.