Pharmacologic treatment of attention-deficit/hyperactivity disorder: Efficacy, safety and mechanisms of action

Studies examining the efficacy, safety and mechanisms of action of agents for the treatment of attention-deficit/hyperactivity disorder (ADHD) are reviewed, with an emphasis on newer agents such as the long acting stimulants and atomoxetine. Recent studies of medications are characterized by large, rigorously diagnosed samples of children, adolescents and adults with ADHD, use of standardized rating scales and extensive safety data. These studies confirm a robust treatment effect for the Food and Drug Administration approved agents ranging from 0.7 to 1.5. The most common short term side effects to the most commonly used agents include insomnia, loss of appetite, and headaches. Despite public controversy and labeling changes to warn of extremely rare cardiovascular and psychiatric side effects, the evidence does not support the hypothesis that medication for ADHD increases risk for sudden death, mania or psychosis. A wide variety of neuroimaging techniques including electrocephalogram (EEG) power, event related potentials (ERP), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET) are beginning to examine the mechanisms of action of medications for ADHD, and implicating the catecholamines and prefrontal and anterior cingulate cortices as prime sites of actions for these agents.