Atomoxetine and Stimulant Medications in Children and Adolescents with Persistent Symptoms of Attention Deficit Hyperactivity Disorder despite Monotherapy

Abstract

Attention deficit hyperactivity disorder (ADHD) is characterized primarily by symptoms of inattention and/or hyperactivity and impulsivity, often leading to behavioural and academic difficulties.1–3 ADHD is the most common neurobehavioural disorder in children and adolescents, affecting up to 8% of this population.1 Those with ADHD are more likely to experience adverse educational, social, emotional and health outcomes than those without the disorder.2,3 Guidelines for the treatment of children with ADHD recognize the importance of pharmacological intervention, with stimulants recommended as first-line therapy in most cases.1,2 Stimulants, such as methylphenidate (MPH), are thought to improve executive functioning by enhancing dopaminergic signalling in the brain.2 About 80% of children experience a response to stimulants.1,3 The remainder of patients may have no response or only a partial response. Those with only a partial response may be unable to tolerate dosage increases because of common adverse drug effects (ADEs) of stimulants, such as insomnia, mood changes and gastrointestinal (GI) symptoms, including reduced appetite and weight loss.1–3 Atomoxetine (ATMX), a selective norepinephrine-reuptake inhibitor, is a relatively new agent. Because of its novel mechanism of action, the combined use of ATMX and stimulants may represent an interesting therapeutic approach for children lacking a complete response to monotherapy. In general, ATMX and MPH have similar efficacy. However, the extended-release formulation of MPH, known as osmotic-release oral system (OROS) MPH (Concerta), is more effective than immediate-release preparations of this drug.4 Longacting stimulant preparations such as OROS MPH are considered first-line treatments for ADHD, whereas short- and intermediate-acting stimulants are considered second-line adjunctive treatments.2,5 ATMX is currently the only nonstimulant medication considered as a first-line agent for the treatment of ADHD in children.2,5