The medical treatment of attention deficit hyperactivity disorder (ADHD) with amphetamines in children and adolescents

Introduction: Psychostimulants (methylphenidate and amphetamines) are the drugs of first choice in the pharmacological treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). Objective: We summarize the pharmacological characteristics of amphetamines and compare them with methylphenidate, special emphasisis being given to a comparison of effects and side effects of the two substances. Finally, we analyze the abuse and addiction risks. Methods: Publications were chosen based on a Medline analysis for controlled studies and meta-analyses published between 1980 and 2011; keywords were amphetamine, amphetamine salts, lisdexamphetamine, controlled studies, and metaanalyses. Results and Discussion: Amphetamines generally exhibit some pharmacologic similarities with methylphenidate. However, besides inhibiting dopamine reuptake amphetamines also cause the release of monoamines. Moreover, plasma half-life is significantly prolonged. The clinical efficacy and tolerability of amphetamines is comparable to methylphenidate. Amphetamines can therefore be used if the individual response to methylphenidate or tolerability is insufficient before switching to a nonstimulant substance, thus improving the total response rate to psychostimulant treatment. Because of the high abuse potential of amphetamines, especially in adults, the prodrug lisdexamphetamine (Vyvanse) could become an effective treatment alternative. Available study data suggest a combination of high clinical effect size with a beneficial pharmacokinetic profile and a reduced abuse risk. Conclusions: In addition to methylphenidate, amphetamines serve as important complements in the psychostimulant treatment of ADHD. Future studies should focus on a differential comparison of the two substances with regard to their effects on different core symptom constellations and the presence of various comorbidities.