New and extended-action treatments in the management of ADHD: a critical appraisal of lisdexamfetamine in adults and children

Treatment guidelines from the American Academy of Child and Adolescent Psychiatry and the American Academy of Pediatrics state that stimulant medications have the most evidence for safety and efficacy in the treatment of childhood attention deficit hyperactivity disorder (ADHD). Longer-acting stimulants are thus considered as first-line for management of ADHD symptoms. Over the years, concerns about the abuse potential of stimulants have led to the development of alternative formulations of these agents. One such recent development, lisdexamfetamine (LDX) was FDA approved for treating ADHD in children in early 2007 and in adults in early 2008. LDX is a prodrug, which when orally ingested, is converted to l- lysine and active d-amphetamine, which is responsible for its therapeutic activity. This unique formulation may lead to a possible reduction of the abuse potential, by bypassing the first-pass metabolism. In fact, a statistically significant difference for the ‘liking’ effects on the Drug Questionnaire Response has been reported with intravenous LDX compared to d-amphetamine. LDX appears to have an efficacy and tolerability profile comparable to other extended-release stimulant formulations used to treat ADHD, but reduced potential for abuse-related liking effects when compared to equivalent amounts of immediate-release d-amphetamine. The most common adverse events include decreased appetite, insomnia, upper abdominal pain, headache, irritability, weight loss, and nausea.