Lisdexamfetamine dimesylate: a prodrug stimulant for the treatment of ADHD in children and adults

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly genetic neuropsychiatric disorder that can cause impairment at school, work, home, and in social relationships. Once considered a childhood disorder, as many as 65% of children with ADHD continue to exhibit symptoms into adulthood. While a mainstay of ADHD patient care, immediate-release stimulant use has been constrained by concerns about safety, tolerability, and issues related to nonmedical use and abuse. These concerns have prompted interest in developing modified versions or new delivery systems for stimulants. Prodrugs have been used in pharmaceutical development to optimize delivery of an active drug or to minimize toxicity. Prodrugs are pharmacologically inactive compounds that require in vivo conversion to release therapeutically active medications. Lisdexamfetamine dimesylate (LDX) is an inactive, water-soluble prodrug in which d-amphetamine is bonded to l-lysine, a naturally occurring amino acid. After oral ingestion, LDX is metabolized into l-lysine and active d-amphetamine. This review of LDX presents the efficacy, safety, and pharmacokinetic profile of this novel stimulant medication, and is intended to help clinicians understand its role in treating children and adults with ADHD.