ADHD is an increasingly recognized disorder and pharmaceutical companies are regularly developing new drugs and new formulations of older drugs in an attempt to gain an increasing share of this lucrative market. Whether the new pharmaceuticals bring actual therapeutic advantage or simply represent new ‘brands’ with similar effectiveness is an ongoing question. Vyvanse (Lisdexamfetamine dimesylate) is the newest arrival on this competitive turf. It was shown to be effective compared to placebo in two clinical trials of children ages 6-12 and in one trial in adults.
Vyvanse is a prodrug formulation of dextroamphetamine. A prodrug is a pharmacological substance (drug) that is administered in an inactive (or significantly less active) form. Once administered, the prodrug is metabolized into an active metabolite. In the case of Vyvanse, this process takes place in the gastrointestinal tract, thus releasing active dextroamphetamine. The active metabolite dextroamphetamine then mediates the therapeutic effect in a fashion similar to other stimulants. Though the mode of therapeutic action in Attention-Deficit/Hyperactivity Disorder (ADHD) is not known, the amphetamines are thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these substances in the brain.
Lisdexamfetamine does not produce high dextroamphetamine levels when injected or snorted, and thus may have lower abuse potential compared to conventional stimulants. Vyvanse was developed specifically in this prodrug formulation with the goal of providing an extended duration of effect that is consistent throughout the day, with a reduced potential for abuse, overdose toxicity, and drug tampering. Side effects were consistent with other psychostimulants, and long term monitoring demonstrated no significant changes in blood pressure or electrocardiographic parameters. There have been no comparative studies between Vyvanse and other stimulants, and it’s duration of effectiveness is similar to other long acting stimulant formulations (8-10 hours). The only circumstances that Vyvanse seems to be more useful in treatment over other stimulants are those in which there is a significant abuse potential. With the possibility of this rather slender exception, our verdict on Vyvanse is that it is more of the same: another long-acting stimulant in a field that is growing in size but not diversity. We look forward to different drug development strategies, perhaps those which derive from a more precise molecular genetic understanding of the neurobiology of ADHD, that will one day generate truly novel and improved therapeutic agents for this disorder.