Pharmacological properties and clinical effects of the ADHD drug, Lisdexamfetamine (Vyvanse^® capsules 20 mg and 30 mg)

Abstract

Lisdexamfetamine dimesylate (hereinafter referred to as “lisdexamfetamine”; brand name, Vyvanse^®), was developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). This drug, which is classified as a central nervous system (CNS) stimulant for once-daily oral administration, received marketing approval in March 2019 and was launched in December 2019 in Japan. Lisdexamfetamine is a prodrug that is hydrolyzed to its active form d-amphetamine in the blood following oral administration. Pharmacologically, d-amphetamine competitively inhibits the dopamine transporter (DAT) and the noradrenaline transporter (NAT) to increase dopamine (DA) and noradrenaline (NA) concentrations in the synaptic cleft. In addition to inhibiting the reuptake of DA and NA, d-amphetamine has also an effect in promoting the release of these neurotransmitters by being taken up into neuronal cells and then acting on the vesicular monoamine transporter. The mechanisms of action by which d-amphetamine exerts a therapeutic effect on ADHD may be based on the above-described effects. Clinical studies conducted in Japan and overseas have demonstrated the efficacy of lisdexamfetamine over placebo in the treatment of pediatric ADHD patients. The most of the adverse events with a higher incidence than in the placebo were mild, and long-term administration of the drug was not associated with an increase in the incidence of adverse events or the rate of treatment discontinuation. Lisdexamfetamine, which is designated as raw material for stimulants and therefore requires strict distribution control in Japan, is expected to be effective in the treatment of ADHD patients with inadequate responses to existing therapeutic agents.