Attention deficit/hyperactivity disorder (ADHD; also known as attention deficit disorder or hyperkinetic disorder) is a complex neuropsychiatric and behavioral disorder characterized by inattentive, hyperactive and impulsive behavior. Although estimates vary widely, the Centers for Disease Control and Prevention (CDC) estimates that nearly 8% of school-age children in the U.S. have ADHD, making this one of the most common behavioral and psychological disorders encountered in pediatric medicine.

Psychostimulant drugs have been used in the treatment of attention deficit/hyperactivity disorder for more than 60 years. The most widely used and well studied psychostimulant is methylphenidate (Ritalin); other drugs in this class include dextroamphetamine and pemoline. Nine out of ten patients improve with psychostimulants. Through their predominantly dopaminergic mechanism of action, drugs in this class produce beneficial effects on the defining symptoms of ADHD (overactivity, attention span, impulsivity, self-control) and associated aggressiveness, although they may not correct all behavior problems. However, psychostimulants may be addictive to adolescents and adults if misused, and this concern has generated significant debate among individuals with ADHD and their families. These drugs are not considered to be addictive in young children; nonetheless, administration of stimulants in the U.S. is closely controlled.

In an attempt to reduce the potential liability of addiction and abuse, New River Pharmaceuticals developed lisdexamfetamine dimesilate, an amphetamine prodrug consisting of d-amphetamine conjugated to L-lysine. The drug is therapeutically inactive until it is hydrolyzed in the digestive tract, and furthermore has a prolonged duration of effect, with efficacy lasting for a full treatment day. Data from phase II and III trials, conducted by New River in collaboration with development partner Shire, demonstrated statistically significant improvements in ADHD symptoms in patients aged 6-12 years receiving lisdexamfetamine at all doses tested (30, 50 and 70 mg) as compared to those given placebo. In human drug abuse studies, oral and intravenous administration of lisdexamfetamine produced subjective responses on a scale of "drug-liking effects" (DLE, a measure of relative preference among substance abusers, used in clinical abuse studies) that were less than those reported for d-amphetamine at equivalent doses.

In February, the U.S. FDA approved lisdexamfetamine dimesilate (Vyvanse®) for the treatment of attention deficit/hyperactivity disorder in pediatric patients. The label received with the approval letter includes information about the drug’s extended duration of effect and abuse-related drug-liking characteristics, which differentiate Vyvanse® from other ADHD medications. The FDA has proposed that Vyvanse® be classified as a Schedule II controlled substance, and this proposal has been accepted by the U.S. Drug Enforcement Administration (DEA). Pending final scheduling designation, product launch is anticipated in the second quarter of 2007. In related news, Shire announced just days prior to the NDA approval that it would acquire New River and, as a result, all rights to the product.