Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is the most prevalent childhood developmental disorder and is also of unclear neurobiological aetiology. However, recent advances in molecular genetics and brain imaging implicate dopaminergic hypofunction in the frontal lobes and basal ganglia in ADHD. Psychostimulants (e.g. methylphenidate and amphetamine, which are potent inhibitors of the dopamine transporter) are the first choice medication for ADHD and have a good acute efficacy and safety profile when used for this disorder. Whether long-term psychostimulant administration to adolescents alters neural development and behaviour or increases the risk of substance abuse is less certain. The precise molecular mechanism of action of psychostimulants is beginning to be established. Furthermore, preclinical studies have begun to use lower clinically relevant doses and oral administration of psychostimulants to determine their long-term effect on development, behaviour and neurochemistry, which is an important public health issue associated with chronic medication of adolescents with ADHD.